BioavailabilityPhase 1NCT02446171
A Bioavailability Study With Alternate Methods of Administration of Naloxegol Tablets, and Solution
A Phase 1 study testing Naloxegol 25 mg tablet, crushed, suspended in water, given orally, Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube and Naloxegol 25 mg (10 mL oral solution) in people with Bioavailability and Healthy Subjects, run by AstraZeneca at 1 site in Germany.
Trial summary
This clinical study is an open-label, randomized, 4-period, 4-treatment, crossover, single-center, single-dose bioavailability study with alternate methods of administration of crushed naloxegol tablets, 25 mg and of a naloxegol solution formulation, 25 mg, compared to whole naloxegol tablets, 25 mg, in healthy… Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Bioavailability, Healthy Subjects
- What is being tested?
- Naloxegol 25 mg tablet, crushed, suspended in water, given orally, Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube and Naloxegol 25 mg (10 mL oral solution)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteGermany
- Study dates
- May 2015to Jul 2015
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Healthy male and female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and on admission to the clinical unit, must not be lactating and must be of non childbearing potential, confirmed at screening by fulfilling one of the following criteria:
- Post-menopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and follicle-stimulating hormone (FSH) levels in the post-menopausal range.
- Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy; but not tubal ligation.
- Have a body mass index (BMI) between 18.5 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Able to understand, read and speak the German language.
Who cannot join
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influence the results or the potential subject's ability to participate in the study.
- Current smokers or those who have smoked or used nicotine products within the previous 3 months.
- Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- Drugs include known CYP3A4 and/or P-gp inhibitors and inducers, e.g., diltiazem, verapamil, and erythromycin
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.
- For females, hormonal replacement therapy is not allowed.
- Subject with a relevant history of a suicide attempt or suicidal behavior. Any recent suicidal ideation within the last 6 months (a level of 4 or 5), or who are at significant risk to commit suicide, as judged by the investigator using the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Applicable to subjects willing to participate in genetic research: Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection or previous bone marrow transplant.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-Label, Randomized, 4-Period, 4-Treatment, Crossover, Single-Center, Single-Dose Bioavailability Study With Alternate Methods of Administration of Crushed Naloxegol Tablets, 25 mg and of a Naloxegol Solution Formulation, 25 mg, Compared to Whole Naloxegol Tablets, 25 mg, in Healthy Subjects
This clinical study is an open-label, randomized, 4-period, 4-treatment, crossover, single-center, single-dose bioavailability study with alternate methods of administration of crushed naloxegol tablets, 25 mg and of a naloxegol solution formulation, 25 mg, compared to whole naloxegol tablets, 25 mg, in healthy subjects.
The main objective of this study is to determine the bioavailability of each of three alternative methods of naloxegol administration compared to whole naloxegol tablets given orally by assessment of the primary pharmacokinetic (PK) parameters of naloxegol
Read the detailed description
This is an open-label, randomized, 4-period, 4-treatment, crossover, single-center, single-dose bioavailability study with alternate methods of administration of naloxegol: crushed and suspended in water and administered orally (Treatment A),crushed and suspended in water administered via nasogastric tube (Treatment B), solution administered orally (Treatment C) and tablet swallowed as a whole (Treatment D).
Alternative ways of administering a tablet may be useful to help patients who, for different reasons, have difficulties with swallowing a whole tablet. Administration of dispersed (crushed) tablets suspended in water is a common way of administering drugs to these patients. A useful method in patients whose condition prevents swallowing is administration of dispersed tablets through nasogastric tubes. Additionally a solution formulation may be an attractive option for some patients including the pediatric population. The main aim in this clinical study is to investigate whether the blood concentrations of naloxegol (pharmacokinetic) after each treatment A, B and C is comparable to that after treatment D. Additionally, the safety and tolerability shall be assessed.
- Conditions
- Bioavailability, Healthy Subjects
- Being tested
- Naloxegol 25 mg tablet, crushed, suspended in water, given orally, Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube, Naloxegol 25 mg (10 mL oral solution), Naloxegol 25 mg tablet, given orally
- Keywords
- naloxegol tablet crushed, naloxegol oral solution, naloxegol whole tablet, relative bioavailability, Phase I, healthy subjects
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naloxegol 25 mg tablet, crushed, suspended in water, given orallyDrug
Also called Treatment A, (Test product)
naloxegol 25 mg (1 tablet) crushed, suspended in water, given orally
Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tubeDrug
Also called Treatment B, (Test product)
naloxegol 25 mg (1 tablet) crushed, suspended in water, given via nasogastric tube
Naloxegol 25 mg (10 mL oral solution)Drug
Also called Treatment C, (Test product)
naloxegol 25 mg (10 mL oral solution)
Naloxegol 25 mg tablet, given orallyDrug
Also called Treatment D, (Reference product)
naloxegol 25 mg (1 tablet) whole tablet, given orally
| Study group | Role | What they receive |
|---|---|---|
| Treatments A-D-B-C sequence | Experimental | Treatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4 Receives: Drug: Naloxegol 25 mg tablet, crushed, suspended in water, given orally; Drug: Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube; Drug: Naloxegol 25 mg (10 mL oral solution); Drug: Naloxegol 25 mg tablet, given orally |
| Treatments B-A-C-D sequence | Experimental | Treatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4 Receives: Drug: Naloxegol 25 mg tablet, crushed, suspended in water, given orally; Drug: Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube; Drug: Naloxegol 25 mg (10 mL oral solution); Drug: Naloxegol 25 mg tablet, given orally |
| Treatments C-B-D-A sequence | Experimental | Treatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4 Receives: Drug: Naloxegol 25 mg tablet, crushed, suspended in water, given orally; Drug: Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube; Drug: Naloxegol 25 mg (10 mL oral solution); Drug: Naloxegol 25 mg tablet, given orally |
| Treatments D-C-A-B sequence | Experimental | Treatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4 Receives: Drug: Naloxegol 25 mg tablet, crushed, suspended in water, given orally; Drug: Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube; Drug: Naloxegol 25 mg (10 mL oral solution); Drug: Naloxegol 25 mg tablet, given orally |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-infinity).
Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) is presented below. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
Measured: Pre-dose (0 hours [within 30 minutes prior to administration of the investigational medicinal product (IMP)]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC 0-t).
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration is presented below. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
Measured: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Observed Maximum Plasma Concentration (Cmax).
Observed maximum plasma concentration (Cmax) is presented below. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
Measured: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Secondary outcomes (14)
Time to Reach Maximum Plasma Concentration (Tmax).
This was one of the PK parameters to determine the time to reach maximum plasma concentration (tmax). Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
Measured: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz).
This was one of the PK parameters to determine λz of a t½λz. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
Measured: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Mean Dissolution Time (MDT).
This was one of the PK parameters to determine MDT (whole tablet only) (calculated as MRT Treatment D [Reference] - MRT Treatment C [Test]). Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
Measured: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Mean Residence Time (MRT).
This was one of the PK parameters to determine MRT. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
Measured: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F).
This was one of the PK parameters to determine the apparent total body clearance after extravascular administration estimated as dose divided by AUC. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
Measured: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F).
This was one of the PK parameters to determine the apparent volume of distribution during the terminal phase after extravascular administration.
Measured: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Percentage of Participants With Adverse Events (AE).
An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product.The term AE is used generally to include any AE whether serious or non-serious. An serious AE (SAE) is an AE that fulfills one or more of the following criteria: results in death, is immediately life-threatening; requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity or substantial disruption of the ability to conduct normal life functions; is a congenital abnormality or birth defect; is an important medical event that may jeopardize the participant or may require medical intervention to prevent one of the outcomes listed above.
Measured: For up to 9 weeks (starting with screening).
Mean Change From Baseline for Vital Signs of Supine Systolic and Diastolic Blood Pressure.
The following variables were collected after the participants had rested in the supine position for at least 5 minutes: Systolic Blood Pressure (SBP) and Diastolic BP. The measurement of vital signs for SBP and DBP are presented in the below outcome table.
Measured: Day 2 (24h post-dose), Day 3 (48h post-dose) and Day 4 (72h post-dose).
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Pulse rate: the measurement of vital signs for pulse rate is presented in the below outcome table.
Measured: Day 2 (24h post-dose), Day 3 (48h post-dose) and Day 4 (72h post-dose).
Participants With Significant Findings in Physical Examination.
A complete physical examination included an assessment of the general appearance, respiratory, cardiovascular, abdomen, skin, head, and neck (including ears, eyes, nose, mouth and throat), lymph nodes, thyroid, musculoskeletal and neurological systems. Physical examination was performed to check for any significant abnormality in participants.
Measured: A full physical examination at screening and the final follow-up visit (maximum 9 weeks apart). Abbreviated physical examination on admission (on Day -1 of each treatment period) and at 48-hours post-dose to each treatment period (for up to 4 weeks).
Participants With Significant Findings in Columbia-Suicide Severity Rating Scale (C-SSRS).
The C-SSRS is a unique, simple and short method of assessing both behavior and ideation that tracks all suicidal events, and provided a summary of suicidality. It assesses the lethality of attempts and other features of ideation (frequency, duration, controllability, reasons for ideation and deterrents), all of which are significantly predictive of completed suicide. The C-SSRS was performed to determine the presence of suicidality.
Measured: At Baseline and Days 1-4 of each treatment period.
Participants With Significant Findings in 12-Lead Electrocardiography (ECG).
A 12-lead ECG was obtained after the participant rested in supine position for at least 10 minutes. The study physician was to judge the overall interpretation as normal or abnormal. If abnormal, it was decided as to whether or not the abnormality was clinically significant and the reason for the abnormality was recorded.
Measured: At screening, first admission to the clinical unit (Visit 2, Day -1), 1.25 hours after each dose (Visits 2-5, Day 1), as well as at the final follow-up visit (up to 9 weeks).
Participants With Significant Findings in Hematology, Clinical Chemistry and Urinalysis.
Participants were assessed through each laboratory variables for any significant abnormalities. Hematology assessments included white blood cell count, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and others. Clinical chemistry assessment included testing levels of sodium, potassium, urea, creatinine, albumin, calcium, glucose (fasting) and others. Urinalysis assessment included glucose, protein, blood and microscopy (if positive for blood or protein).
Measured: At screening and at the final follow-up visit (maximum 9 weeks apart); in addition, for the first and third treatment period at pre-dose.
Taste Test Assessment.
A standardized questionnaire was provided to participants and were asked to complete the questionnaire for the liquid formulations tested, i.e., Naloxegol crushed tablet, oral (Treatment A) and Naloxegol oral solution (Treatment C), without assistance or influence from site personnel. For each formulation, the questionnaire was identical and required the participant's opinion. Sweet, salty, sour, bitter, metallic, hot/spicy were rated on a scale of 0 to 10, where 0 means not at all and 10 means extreme. The overall rating of the taste was rated on a scale of 0 to 10, where 0 means "I dislike it extremely much" and 10 means "I like it extremely much". The smell of the medicine was based on a scale of 0 to 10, where 0 means extremely bad and 10 means extremely nice. The question on whether the participants would consider ever taking the medicine again was based on a scale of 0 to 10, where 0 means "Never - under no circumstances" and 10 means "Yes, definitely".
Measured: Within 1 hour after dosing (Treatments A and C only).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2015 (estimated)
- Study startMay 2015
- Primary completionJul 2015
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for BioavailabilityStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Rainard Fuhr, Dr. med., Principal investigator, PAREXEL International GmbH, Berlin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02446171
- Sponsor's protocol ID
- D3820C00035
- Status last verified
- Jan 2017
- First submitted
- 29 Apr 2015
- Last updated
- 10 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bui K, Birmingham B, Diva U, Berger B. An Open-Label, Randomized Bioavailability Study of Alternative Methods of Oral Administration of Naloxegol in Healthy Subjects. Clin Pharmacol Drug Dev. 2017 Jul;6(4):420-427. doi: 10.1002/cpdd.335. Epub 2017 Jan 27.
PubMed 28127938
Study at a glance
From the registry record, last updated by the sponsor on 10 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Randomized, 4-Period, 4-Treatment, Crossover, Single-Center, Single-Dose Bioavailability Study With Alternate Methods of Administration of Crushed Naloxegol Tablets, 25 mg and of a Naloxegol Solution Formulation, 25 mg, Compared to Whole Naloxegol Tablets, 25 mg, in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02446171
- Acronym / sponsor ID
- D3820C00035
- Conditions
- Bioavailability, Healthy Subjects
- Keywords
- naloxegol tablet crushed, naloxegol oral solution, naloxegol whole tablet, relative bioavailability, Phase I, healthy subjects
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- May 2015
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 18 May 2015 (estimated)
- Results
- Posted 9 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical study is an open-label, randomized, 4-period, 4-treatment, crossover, single-center, single-dose bioavailability study with alternate methods of administration of crushed naloxegol tablets, 25 mg and of a naloxegol solution formulation, 25 mg, compared to whole naloxegol tablets, 25 mg, in healthy subjects.
The main objective of this study is to determine the bioavailability of each of three alternative methods of naloxegol administration compared to whole naloxegol tablets given orally by assessment of the primary pharmacokinetic (PK) parameters of naloxegol
Detailed description
This is an open-label, randomized, 4-period, 4-treatment, crossover, single-center, single-dose bioavailability study with alternate methods of administration of naloxegol: crushed and suspended in water and administered orally (Treatment A),crushed and suspended in water administered via nasogastric tube (Treatment B), solution administered orally (Treatment C) and tablet swallowed as a whole (Treatment D).
Alternative ways of administering a tablet may be useful to help patients who, for different reasons, have difficulties with swallowing a whole tablet. Administration of dispersed (crushed) tablets suspended in water is a common way of administering drugs to these patients. A useful method in patients whose condition prevents swallowing is administration of dispersed tablets through nasogastric tubes. Additionally a solution formulation may be an attractive option for some patients including the pediatric population. The main aim in this clinical study is to investigate whether the blood concentrations of naloxegol (pharmacokinetic) after each treatment A, B and C is comparable to that after treatment D. Additionally, the safety and tolerability shall be assessed.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatments A-D-B-C sequence | Experimental | Drug: Naloxegol 25 mg tablet, crushed, suspended in water, given orally, Drug: Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube, Drug: Naloxegol 25 mg (10 mL oral solution), Drug: Naloxegol 25 mg tablet, given orallyTreatment A in Period 1, Treatment D in Period 2, Treatment B in Period 3 and Treatment C in Period 4 |
| Treatments B-A-C-D sequence | Experimental | Drug: Naloxegol 25 mg tablet, crushed, suspended in water, given orally, Drug: Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube, Drug: Naloxegol 25 mg (10 mL oral solution), Drug: Naloxegol 25 mg tablet, given orallyTreatment B in Period 1, Treatment A in Period 2, Treatment C in Period 3 and Treatment D in Period 4 |
| Treatments C-B-D-A sequence | Experimental | Drug: Naloxegol 25 mg tablet, crushed, suspended in water, given orally, Drug: Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube, Drug: Naloxegol 25 mg (10 mL oral solution), Drug: Naloxegol 25 mg tablet, given orallyTreatment C in Period 1, Treatment B in Period 2, Treatment D in Period 3 and Treatment A in Period 4 |
| Treatments D-C-A-B sequence | Experimental | Drug: Naloxegol 25 mg tablet, crushed, suspended in water, given orally, Drug: Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube, Drug: Naloxegol 25 mg (10 mL oral solution), Drug: Naloxegol 25 mg tablet, given orallyTreatment D in Period 1, Treatment C in Period 2, Treatment A in Period 3 and Treatment B in Period 4 |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Healthy male and female subjects aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
- Females must have a negative pregnancy test at screening and on admission to the clinical unit, must not be lactating and must be of non childbearing potential, confirmed at screening by fulfilling one of the following criteria:
- Have a body mass index (BMI) between 18.5 and 29.9 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
- Able to understand, read and speak the German language.
Key exclusion criteria (8 listed)
- History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the potential subject at risk because of participation in the study, or influence the results or the potential subject's ability to participate in the study.
- Current smokers or those who have smoked or used nicotine products within the previous 3 months.
- Use of drugs with enzyme-inducing properties such as St John's Wort within 3 weeks prior to the first administration of IMP.
- Drugs include known CYP3A4 and/or P-gp inhibitors and inducers, e.g., diltiazem, verapamil, and erythromycin
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose) and minerals during 2 weeks prior to the first administration of IMP or longer if the medication has a long half-life.
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 |
|---|---|---|
| Naloxegol 25 mg tablet, crushed, suspended in water, given orallyAlso: Treatment A, (Test product)naloxegol 25 mg (1 tablet) crushed, suspended in water, given orally | Drug | Treatments A-D-B-C sequence, Treatments B-A-C-D sequence, Treatments C-B-D-A sequence, Treatments D-C-A-B sequence |
| Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tubeAlso: Treatment B, (Test product)naloxegol 25 mg (1 tablet) crushed, suspended in water, given via nasogastric tube | Drug | Treatments A-D-B-C sequence, Treatments B-A-C-D sequence, Treatments C-B-D-A sequence, Treatments D-C-A-B sequence |
| Naloxegol 25 mg (10 mL oral solution)Also: Treatment C, (Test product)naloxegol 25 mg (10 mL oral solution) | Drug | Treatments A-D-B-C sequence, Treatments B-A-C-D sequence, Treatments C-B-D-A sequence, Treatments D-C-A-B sequence |
| Naloxegol 25 mg tablet, given orallyAlso: Treatment D, (Reference product)naloxegol 25 mg (1 tablet) whole tablet, given orally | Drug | Treatments A-D-B-C sequence, Treatments B-A-C-D sequence, Treatments C-B-D-A sequence, Treatments D-C-A-B sequence |
Primary outcome
Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-infinity).
Time frame: Pre-dose (0 hours [within 30 minutes prior to administration of the investigational medicinal product (IMP)]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Area under plasma concentration-time curve from time zero extrapolated to infinity (AUC) is presented below. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC 0-t).
Time frame: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration is presented below. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
Observed Maximum Plasma Concentration (Cmax).
Time frame: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Observed maximum plasma concentration (Cmax) is presented below. Blood was collected pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours post-dose to determine naloxegol plasma concentrations.
14 secondary outcomes
Time to Reach Maximum Plasma Concentration (Tmax).
Time frame: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t½λz).
Time frame: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Mean Dissolution Time (MDT).
Time frame: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Mean Residence Time (MRT).
Time frame: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Apparent Total Body Clearance After Extravascular Administration Estimated as Dose Divided by AUC (CL/F).
Time frame: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Apparent Volume of Distribution During the Terminal Phase After Extravascular Administration (Vz/F).
Time frame: Pre-dose (0 hours [within 30 minutes prior to IMP administration]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.
Percentage of Participants With Adverse Events (AE).
Time frame: For up to 9 weeks (starting with screening).
Mean Change From Baseline for Vital Signs of Supine Systolic and Diastolic Blood Pressure.
Time frame: Day 2 (24h post-dose), Day 3 (48h post-dose) and Day 4 (72h post-dose).
Mean Change From Baseline for Vital Signs in Supine Pulse Rate.
Time frame: Day 2 (24h post-dose), Day 3 (48h post-dose) and Day 4 (72h post-dose).
Participants With Significant Findings in Physical Examination.
Time frame: A full physical examination at screening and the final follow-up visit (maximum 9 weeks apart). Abbreviated physical examination on admission (on Day -1 of each treatment period) and at 48-hours post-dose to each treatment period (for up to 4 weeks).
Participants With Significant Findings in Columbia-Suicide Severity Rating Scale (C-SSRS).
Time frame: At Baseline and Days 1-4 of each treatment period.
Participants With Significant Findings in 12-Lead Electrocardiography (ECG).
Time frame: At screening, first admission to the clinical unit (Visit 2, Day -1), 1.25 hours after each dose (Visits 2-5, Day 1), as well as at the final follow-up visit (up to 9 weeks).
Participants With Significant Findings in Hematology, Clinical Chemistry and Urinalysis.
Time frame: At screening and at the final follow-up visit (maximum 9 weeks apart); in addition, for the first and third treatment period at pre-dose.
Taste Test Assessment.
Time frame: Within 1 hour after dosing (Treatments A and C only).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 28127938Bui K, Birmingham B, Diva U, Berger B. An Open-Label, Randomized Bioavailability Study of Alternative Methods of Oral Administration of Naloxegol in Healthy Subjects. Clin Pharmacol Drug Dev. 2017 Jul;6(4):420-427. doi: 10.1002/cpdd.335. Epub 2017 Jan 27.
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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.
Rainard Fuhr, Dr. med. principal investigator
PAREXEL International GmbH, Berlin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Naloxegol 25 mg tablet, crushed, suspended in water, given orally, Naloxegol 25mg tablet crushed, suspended in water, given via nasogastric tube and Naloxegol 25 mg (10 mL oral solution) in people with Bioavailability and Healthy Subjects, run by AstraZeneca at 1 site in Germany.
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 6 inclusion and 8 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 10 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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?
Yes. Results are posted in the registry (first posted 9 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Area Under Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-infinity). (time frame: Pre-dose (0 hours [within 30 minutes prior to administration of the investigational medicinal product (IMP)]) and post-dose at 0.25 (15 minutes), 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours in each treatment period.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02446171, which also lists 1 linked publication.
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 10 Mar 2017.