PharmacokineticPhase 1NCT03882762
A Clinical Study to Evaluate the Effect of Renal Impairment on the Pharmacokinetics of Cebranopadol
A Phase 1 study testing Cebranopadol 200 μg tablet in people with Pharmacokinetic, run by Tris Pharma, Inc. at 2 sites in United States.
Trial summary
The objective of this study was to evaluate the pharmacokinetics (PK), safety and tolerability profile of cebranopadol (GRT6005) in patients with varying degree of renal impairment and participants with normal renal function after an oral single dose administration. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetic
- What is being tested?
- Cebranopadol 200 μg tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 Jun 2013to 17 Sep 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Common criteria:
- Sign the informed consent form (ICF) and have the mental capability to understand it.
- Be male or female, aged 18 through 75 years.
- If female, have a negative result from a serum pregnancy test at screening and a negative result from a serum or urine pregnancy test on Day -1.
- If male, agree to use an effective method of contraception (i.e., condom plus diaphragm with spermicide or condom plus spermicide) and not have their partners become pregnant throughout the study, or have been sterilized for at least 1 year (with supporting documentation of the absence of sperm in the ejaculate postvasectomy).
- If female of childbearing potential, agree to use an effective method of contraception (i.e., condom plus diaphragm with spermicide, condom plus spermicide, or nonhormonal intrauterine device) and not become pregnant throughout the study. Females who are at least 2-years postmenopausal (with supporting documentation from an obstetrician/gynecologist) or who have had tubal ligation or hysterectomy (with supporting documentation from the physician who performed the surgery) will not be considered to be of childbearing potential.
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- Be nonsmoking (never smoked or have not smoked within the previous 2 years) or light smokers (less than or equal to 10 cigarettes per day within the previous 3 months).
- Have a sitting pulse rate greater than or equal to 50 beats per minute (bpm) or less than or equal to 100 bpm during the vital sign assessment at screening.
- Have a body mass index (BMI) greater than or equal to 18 kilograms per square meter and less than or equal to 42 kilograms per square meter.
- Participants with Renal Impairment:
- Have results of medical history, physical examination, and laboratory and other test results consistent with their degree of renal impairment, as determined by the Investigator.
- Have an estimated glomerular filtration rate (eGFR) of 60-89 mL/min/1.73m2 (Group I); 30-59 mL/min/1.73m2 (Group II); and 15-29 mL/min/1.73 m2 (Group III). The maximum allowable intra-subject variability based on the 2 determinations of eGFR at screening and Day -1 using the Modification of Diet in Renal Disease (MDRD) equation is +/- 30%. If eGFR falls in different categories at screening and on Day -1, the Day -1 eGFR will be used for assignment to the renal impaired group.
- If receiving concomitant medications to treat underlying diseases or medical conditions related to renal insufficiency, must be on stable dosages of these medications for at least 8 weeks before screening.
- Participants with Normal Renal Function:
- Have an eGFR greater than or equal to 90 mL/min/1.73 m2 at screening and on Day -1. The maximum allowable intra-subject variability based on the 2 determinations of eGFR at screening and Day -1 using the MDRD equation is +/- 30 percent. If eGFR falls in different categories at screening and Day -1, the Day -1 eGFR will be used to assign participant to study group.
Who cannot join
- Common criteria:
- Known hypersensitivity to cebranopadol or other opioids.
- Abnormal ECG results thought to be potentially clinically significant according to the Investigator, or QT prolongation (QTcF greater than or equal to 450 msec; uncorrected QT greater than 500 msec).
- Positive test results for anti-human immunodeficiency virus type 1, hepatitis B surface antigen, hepatitis B core antibodies, or anti-hepatitis C virus at screening.
- History of alcohol or other substance abuse within the previous 5 years.
- Positive test results for benzoylecgonine (cocaine), methadone, barbiturates, amphetamines, benzodiazepines, alcohol, cannabinoids, opiates, or phencyclidine at screening or Day -1.
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- Participation in any other clinical investigation using an experimental drug requiring repeated blood or plasma draws within 60 days of investigational product (IP) administration.
- Participation in a blood or plasma donation program within 60 or 30 days, respectively, of IP administration.
- Consumption of caffeine within 48 hours or consumption of alcohol within 72 hours before administration of IP.
- Consumption of beverages or food containing quinine (bitter lemon, tonic water) or any grapefruit-containing products, Seville oranges, or poppy seeds within 14 days before administration of IP.
- Any clinical condition or previous surgery that might affect the absorption, distribution, biotransformation, or excretion of cebranopadol.
- Employee, or immediate relative of an employee, of Forest Laboratories, Inc., any of its affiliates or partners, or the study center.
- Previously taken cebranopadol or previously participated in an investigational study of cebranopadol, unless otherwise authorized by the sponsor.
- Breastfeeding.
- Participants with Renal Impairment:
- Clinically significant disease state, in the opinion of the examining physician, in any body system (other than renal function impairment or concomitant conditions for participants in groups I-III). Medical history, physical examination findings, and abnormal findings on electrocardiogram (ECG) and laboratory analyses should be reviewed, and the participant judged acceptable for participation in this study by the Investigator and Forest Medical Monitor.
- Sitting systolic blood pressure (BP) greater than or equal to 165 mm Hg or less than or equal to 95 mm Hg or sitting diastolic BP greater than or equal to 90 mm Hg or less than or equal to 50 mm Hg at screening.
- Abnormal and clinically significant results on physical examination, medical history, serum chemistry, hematology, or urinalysis with the exception of findings that are related to the renal disease process.
- Have undergone renal transplantation or had renal carcinoma within 1 year before screening.
- Have any evidence of skin lesions, diabetic foot, clinically significant edema states not judged to be related to renal failure, peripheral arterial disease, or epilepsy. (Edema [1+ to 3+ pitting] is allowed).
- History of or risks for acute pancreatitis or exacerbation of pancreatitis.
- Have taken any concomitant medications, with the exception of those medications prescribed as standard therapy for renal disease or other stable concomitant conditions, including over-the-counter medications, within 14 days before IP administration or hormonal drug products (except thyroid supplements) within 30 days before IP administration.
- Participants with Normal Renal Function:
- Clinically significant disease state, in the opinion of the examining physician, in any body system.
- Sitting systolic BP greater than or equal to 140 mm Hg or less than or equal to 90 mm Hg or sitting diastolic BP greater than or equal to 90 mm Hg or less than or equal to 50 mm Hg at screening.
- Abnormal and clinically significant results on physical examination, medical history, oxygen saturation, serum chemistry, hematology, or urinalysis.
- Taken any concomitant medications (including over-the-counter medications) within 14 days or hormonal drug products (except thyroid supplements) within 30 days before administration of IP.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
US0001 Contract research organization
Miami, Florida, 33014-3616
US0002 Contract research organization
Orlando, Florida, 32809
About this study
Official title: A Non-randomized, Single-dose, Open-Label, Pharmacokinetic Study of Cebranopadol in Patients With Impaired Renal Function and Subjects With Normal Renal Function
The objective of this study was to evaluate the pharmacokinetics (PK), safety and tolerability profile of cebranopadol (GRT6005) in patients with varying degree of renal impairment and participants with normal renal function after an oral single dose administration.
This study was a Phase 1, multi-center, non-randomized, open-label, parallel group, single-dose study in up to 24 male and female patients with varying degree of renal impairment and participants with normal renal function.
Read more
Within 14 days before the administration of cebranopadol the general eligibility of the participants for the study was assessed according to the inclusion/exclusion criteria. Estimated glomerular filtration rate (eGFR) was determined according to the Modification of Diet in Renal Disease (MDRD) equation.
A treatment period from Day -1 to Day 8 was performed, with participant confinement to the study site from Day -1 to Day 6 and an outpatient visit on Day 8. A single dose of cebranopadol 200 μg was administered on Day 1. Multiple blood and urine samples were drawn for pharmacokinetic evaluations and safety laboratory monitoring. Additional blood samples were taken prior investigational medicinal product (IMP) administration to assess serum creatinine concentration and protein binding.
An End-of-Trial Visit was performed at the time, or within 7 days, of the final blood sample on Day 8 or at early withdrawal.
- Conditions
- Pharmacokinetic
- Being tested
- Cebranopadol 200 μg tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cebranopadol 200 μg tabletDrug
200 μg cebranopadol film-coated tablet was taken with 240 mL of water under fed conditions.
| Study group | Role | What they receive |
|---|---|---|
| Group I - Cebranopadol 200 μg tablet | Experimental | Mild Renal Impairment:
PK evaluable non-dialyzed patients with mildly impaired renal function (eGFR = 60-89 mL/min/1.73 m2) Receives: Drug: Cebranopadol 200 μg tablet |
| Group II - Cebranopadol 200 μg tablet | Experimental | Moderate Renal Impairment:
PK evaluable non-dialyzed patients with moderately impaired renal function (eGFR = 30-59 mL/min/1.73 m2) Receives: Drug: Cebranopadol 200 μg tablet |
| Group III - Cebranopadol 200 μg tablet | Experimental | Severe Renal Impairment:
PK evaluable non-dialyzed patients with severely impaired renal function (eGFR = 15-29 mL/min/1.73 m2) Receives: Drug: Cebranopadol 200 μg tablet |
| Group IV - Cebranopadol 200 μg tablet | Experimental | Normal Renal Function:
PK evaluable participants with normal renal function (eGFR greater than or equal to 90 mL/min/1.73 m2) Receives: Drug: Cebranopadol 200 μg tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic parameter Plasma: maximum plasma concentration (Cmax) for Cebranopadol (GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: maximum plasma concentration (Cmax) for M2 (7-hydroxy GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: maximum plasma concentration (Cmax) for M3 (N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: maximum plasma concentration (Cmax) for M6 (7-hydroxy N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: time to maximum plasma concentration (tmax) for Cebranopadol (GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The time to maximum cebranopadol and its metabolites plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: time to maximum plasma concentration (tmax) for M2 (7-hydroxy GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The time to maximum cebranopadol and its metabolites plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: time to maximum plasma concentration (tmax) for M3 (N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The time to maximum cebranopadol and its metabolites plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: time to maximum plasma concentration (tmax) for M6 (7-hydroxy N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The time to maximum cebranopadol and its metabolites plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve from 0 to time t (AUC0-t) for Cebranopadol (GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve from 0 to time t (AUC0-t) for M2 (7-hydroxy GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve from 0 to time t (AUC0-t) for M3 (N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve from 0 to time t (AUC0-t) for M6 (7-hydroxy N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: the half-life associated with the terminal elimination phase (t1/2,z) for Cebranopadol (GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The half-life associated with the terminal elimination phase was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: the half-life associated with the terminal elimination phase (t1/2,z) for M2 (7-hydroxy GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The half-life associated with the terminal elimination phase was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: the half-life associated with the terminal elimination phase (t1/2,z) for M3 (N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The half-life associated with the terminal elimination phase was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: the half-life associated with the terminal elimination phase (t1/2,z) for M6 (7-hydroxy N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The half-life associated with the terminal elimination phase was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf) for Cebranopadol (GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf) for M2 (7-hydroxy GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf) for M3 (N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf) for M6 (7-hydroxy N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: extrapolated part of area under the plasma concentration-time curve (AUCt-inf) for Cebranopadol (GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUCt-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: extrapolated part of area under the plasma concentration-time curve (AUCt-inf) for M2 (7-hydroxy GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUCt-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: extrapolated part of area under the plasma concentration-time curve (AUCt-inf) for M3 (N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUCt-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: extrapolated part of area under the plasma concentration-time curve (AUCt-inf) for M6 (7-hydroxy N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUCt-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for Cebranopadol (GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC%extr was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for M2 (7-hydroxy GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC%extr was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for M3 (N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC%extr was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for M6 (7-hydroxy N-desmethyl-GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC%extr was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: apparent clearance after oral administration (CL/f) for Cebranopadol (GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The CL/f was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Plasma: apparent volume of distribution after oral administration (Vz/f) for Cebranopadol (GRT6005)
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Vz/f was calculated based on plasma concentration-time data (using the actual blood sampling times).
Measured: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t (Ae0-t) for Cebranopadol (GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t (Ae0-t) for M2 (7-hydroxy GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t (Ae0-t) for M3 (N-desmethyl-GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t (Ae0-t) for M6 (7-hydroxy N-desmethyl-GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t expressed as a percentage of the dose (Ae%0-t) for Cebranopadol (GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae%0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t expressed as a percentage of the dose (Ae%0-t) for M2 (7-hydroxy GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae%0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t expressed as a percentage of the dose (Ae%0-t) for M3 (N-desmethyl-GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae%0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t expressed as a percentage of the dose (Ae%0-t) for M6 (7-hydroxy N-desmethyl-GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae%0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: renal clearance of drug from plasma (CLR) for Cebranopadol (GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The CLR was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: renal clearance of drug from plasma (CLR) for M2 (7-hydroxy GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The CLR was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: renal clearance of drug from plasma (CLR) for M3 (N-desmethyl-GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The CLR was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: renal clearance of drug from plasma (CLR) for M6 (7-hydroxy N-desmethyl-GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The CLR was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: rate of renal excretion within collection period ti - tj (r) for Cebranopadol (GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The r was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: rate of renal excretion within collection period ti - tj (r) for M2 (7-hydroxy GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The r was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: rate of renal excretion within collection period ti - tj (r) for M3 (N-desmethyl-GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The r was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Pharmacokinetic parameter Urine: rate of renal excretion within collection period ti - tj (r) for M6 (7-hydroxy N-desmethyl-GRT6005)
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The r was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Measured: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
Secondary outcomes (1)
Safety and tolerability of Cebranopadol (GRT6005): Number of participants with treatment emergent adverse events
Number of participants with treatment emergent adverse events. Treatment emergent adverse events were collected from dosing of IMP up to Day 8.
Measured: Day 1 to Day 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2019
- Study start20 Jun 2013
- Primary completion17 Sep 2014
- Study completion17 Sep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PharmacokineticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tris Pharma, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Forest Laboratories
- Responsible party
- Sponsor
- Investigators
- Study Director Grünenthal GmbH, Study director, Grünenthal GmbH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03882762
- Sponsor's protocol ID
- GRT-PK-07
- Status last verified
- Jul 2021
- First submitted
- 18 Mar 2019
- Last updated
- 15 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Non-randomized, Single-dose, Open-Label, Pharmacokinetic Study of Cebranopadol in Patients With Impaired Renal Function and Subjects With Normal Renal Function
- ClinicalTrials.gov ID
- NCT03882762
- Acronym / sponsor ID
- GRT-PK-07
- Conditions
- Pharmacokinetic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Tris Pharma, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Forest Laboratories
- Study start
- 20 Jun 2013 (actual)
- Primary completion
- 17 Sep 2014 (actual)
- Study completion
- 17 Sep 2014 (actual)
- First posted
- 20 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objective of this study was to evaluate the pharmacokinetics (PK), safety and tolerability profile of cebranopadol (GRT6005) in patients with varying degree of renal impairment and participants with normal renal function after an oral single dose administration.
This study was a Phase 1, multi-center, non-randomized, open-label, parallel group, single-dose study in up to 24 male and female patients with varying degree of renal impairment and participants with normal renal function.
Within 14 days before the administration of cebranopadol the general eligibility of the participants for the study was assessed according to the inclusion/exclusion criteria. Estimated glomerular filtration rate (eGFR) was determined according to the Modification of Diet in Renal Disease (MDRD) equation.
A treatment period from Day -1 to Day 8 was performed, with participant confinement to the study site from Day -1 to Day 6 and an outpatient visit on Day 8. A single dose of cebranopadol 200 μg was administered on Day 1. Multiple blood and urine samples were drawn for pharmacokinetic evaluations and safety laboratory monitoring. Additional blood samples were taken prior investigational medicinal product (IMP) administration to assess serum creatinine concentration and protein binding.
An End-of-Trial Visit was performed at the time, or within 7 days, of the final blood sample on Day 8 or at early withdrawal.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group I - Cebranopadol 200 μg tablet | Experimental | Drug: Cebranopadol 200 μg tabletMild Renal Impairment: PK evaluable non-dialyzed patients with mildly impaired renal function (eGFR = 60-89 mL/min/1.73 m2) |
| Group II - Cebranopadol 200 μg tablet | Experimental | Drug: Cebranopadol 200 μg tabletModerate Renal Impairment: PK evaluable non-dialyzed patients with moderately impaired renal function (eGFR = 30-59 mL/min/1.73 m2) |
| Group III - Cebranopadol 200 μg tablet | Experimental | Drug: Cebranopadol 200 μg tabletSevere Renal Impairment: PK evaluable non-dialyzed patients with severely impaired renal function (eGFR = 15-29 mL/min/1.73 m2) |
| Group IV - Cebranopadol 200 μg tablet | Experimental | Drug: Cebranopadol 200 μg tabletNormal Renal Function: PK evaluable participants with normal renal function (eGFR greater than or equal to 90 mL/min/1.73 m2) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Sign the informed consent form (ICF) and have the mental capability to understand it.
- Be male or female, aged 18 through 75 years.
- If female, have a negative result from a serum pregnancy test at screening and a negative result from a serum or urine pregnancy test on Day -1.
- If male, agree to use an effective method of contraception (i.e., condom plus diaphragm with spermicide or condom plus spermicide) and not have their partners become pregnant throughout the study, or have been sterilized for at least 1 year (with supporting documentation of the absence of sperm in the ejaculate postvasectomy).
- If female of childbearing potential, agree to use an effective method of contraception (i.e., condom plus diaphragm with spermicide, condom plus spermicide, or nonhormonal intrauterine device) and not become pregnant throughout the study. Females who are at least 2-years postmenopausal (with supporting documentation from an obstetrician/gynecologist) or who have had tubal ligation or hysterectomy (with supporting documentation from the physician who performed the surgery) will not be considered to be of childbearing potential.
Key exclusion criteria (27 listed)
- Known hypersensitivity to cebranopadol or other opioids.
- Abnormal ECG results thought to be potentially clinically significant according to the Investigator, or QT prolongation (QTcF greater than or equal to 450 msec; uncorrected QT greater than 500 msec).
- Positive test results for anti-human immunodeficiency virus type 1, hepatitis B surface antigen, hepatitis B core antibodies, or anti-hepatitis C virus at screening.
- History of alcohol or other substance abuse within the previous 5 years.
- Positive test results for benzoylecgonine (cocaine), methadone, barbiturates, amphetamines, benzodiazepines, alcohol, cannabinoids, opiates, or phencyclidine at screening or Day -1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cebranopadol 200 μg tablet200 μg cebranopadol film-coated tablet was taken with 240 mL of water under fed conditions. | Drug | Group I - Cebranopadol 200 μg tablet, Group II - Cebranopadol 200 μg tablet, Group III - Cebranopadol 200 μg tablet, Group IV - Cebranopadol 200 μg tablet |
Primary outcome
Pharmacokinetic parameter Plasma: maximum plasma concentration (Cmax) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Pharmacokinetic parameter Plasma: maximum plasma concentration (Cmax) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Pharmacokinetic parameter Plasma: maximum plasma concentration (Cmax) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Pharmacokinetic parameter Plasma: maximum plasma concentration (Cmax) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. Cmax was calculated based on plasma concentration-time data (using actual blood sampling times).
Pharmacokinetic parameter Plasma: time to maximum plasma concentration (tmax) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The time to maximum cebranopadol and its metabolites plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Pharmacokinetic parameter Plasma: time to maximum plasma concentration (tmax) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The time to maximum cebranopadol and its metabolites plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Pharmacokinetic parameter Plasma: time to maximum plasma concentration (tmax) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The time to maximum cebranopadol and its metabolites plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Pharmacokinetic parameter Plasma: time to maximum plasma concentration (tmax) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The time to maximum cebranopadol and its metabolites plasma concentration was calculated based on plasma concentration-time data (using actual blood sampling times).
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve from 0 to time t (AUC0-t) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve from 0 to time t (AUC0-t) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve from 0 to time t (AUC0-t) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve from 0 to time t (AUC0-t) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-t was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: the half-life associated with the terminal elimination phase (t1/2,z) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The half-life associated with the terminal elimination phase was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: the half-life associated with the terminal elimination phase (t1/2,z) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The half-life associated with the terminal elimination phase was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: the half-life associated with the terminal elimination phase (t1/2,z) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The half-life associated with the terminal elimination phase was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: the half-life associated with the terminal elimination phase (t1/2,z) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The half-life associated with the terminal elimination phase was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: area under the plasma concentration-time curve extrapolated to infinity (AUC0-inf) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC0-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: extrapolated part of area under the plasma concentration-time curve (AUCt-inf) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUCt-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: extrapolated part of area under the plasma concentration-time curve (AUCt-inf) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUCt-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: extrapolated part of area under the plasma concentration-time curve (AUCt-inf) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUCt-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: extrapolated part of area under the plasma concentration-time curve (AUCt-inf) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUCt-inf was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC%extr was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC%extr was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC%extr was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: extrapolated AUC expressed as a percentage of total AUC0-inf (AUC%extr) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The AUC%extr was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: apparent clearance after oral administration (CL/f) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The CL/f was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Plasma: apparent volume of distribution after oral administration (Vz/f) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose
PK blood samples were collected before administration of the IMP and for 168 hours after dosing; 18 PK blood samples were obtained from each participant. Plasma concentrations for cebranopadol were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Vz/f was calculated based on plasma concentration-time data (using the actual blood sampling times).
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t (Ae0-t) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t (Ae0-t) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t (Ae0-t) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t (Ae0-t) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t expressed as a percentage of the dose (Ae%0-t) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae%0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t expressed as a percentage of the dose (Ae%0-t) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae%0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t expressed as a percentage of the dose (Ae%0-t) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae%0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: cumulative amount of unchanged drug excreted into the urine from time 0 to time t expressed as a percentage of the dose (Ae%0-t) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The Ae%0-t was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: renal clearance of drug from plasma (CLR) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The CLR was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: renal clearance of drug from plasma (CLR) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The CLR was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: renal clearance of drug from plasma (CLR) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The CLR was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: renal clearance of drug from plasma (CLR) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The CLR was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: rate of renal excretion within collection period ti - tj (r) for Cebranopadol (GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The r was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: rate of renal excretion within collection period ti - tj (r) for M2 (7-hydroxy GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The r was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: rate of renal excretion within collection period ti - tj (r) for M3 (N-desmethyl-GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The r was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
Pharmacokinetic parameter Urine: rate of renal excretion within collection period ti - tj (r) for M6 (7-hydroxy N-desmethyl-GRT6005)
Time frame: Pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 , and 96-120 hours intervals post-dose
10 PK urine samples were obtained from each participant. Urine concentrations for cebranopadol and its metabolites were determined using validated high-performance liquid chromatography-tandem mass spectrometry bioanalytical assays. The r was calculated based on urine concentration-time data (using the actual urine sampling time intervals).
1 secondary outcome
Safety and tolerability of Cebranopadol (GRT6005): Number of participants with treatment emergent adverse events
Time frame: Day 1 to Day 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director Grünenthal GmbH study director
Grünenthal GmbH
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cebranopadol 200 μg tablet in people with Pharmacokinetic, run by Tris Pharma, Inc. at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetic parameter Plasma: maximum plasma concentration (Cmax) for Cebranopadol (GRT6005) (time frame: Pre-dose and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 and 168 hours post-dose). The study lists 46 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2021.