HemodialysisPhase 1NCT03947970
Study to Evaluate the Pharmacokinetics and Metabolism of [14C] CR845 (Difelikefalin) in Patients With End Stage Renal Disease on Hemodialysis and in Healthy Subjects
A Phase 1 study testing [14C] CR845 in people with Hemodialysis and Healthy, run by Cara Therapeutics, Inc. at 1 site in United States.
Trial summary
The objectives of this study are to evaluate the in vivo metabolite profiling and characterization of CR845 administered intravenously (IV) in patients on hemodialysis (HD) and in healthy subjects; and to determine the pharmacokinetics of radiolabeled [14C] CR845 administered as a single IV bolus in patients on HD and… Read more about this study
- Who is it for?
- Ages 18 years and older, men onlyHealthy volunteers can take part
- Conditions the study is for
- Hemodialysis, Healthy
- What is being tested?
- [14C] CR845
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jan 2019to 6 Apr 2019
- 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 years and older
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Body mass index (BMI) within the range of 18 to 30 kg/m2, inclusive, and body weight not less than 75 kg;
- Vital signs at Screening must be within the following ranges and stable (measured in sitting position after at least 5 minutes' rest);
- Systolic blood pressure (SBP) ≥100 and ≤140 mmHg;
- Diastolic blood pressure (DBP) ≥50 and ≤90 mmHg;
- Heart rate (HR) ≥50 and ≤100 beats per minute (bpm).
- Must be in good health as determined by past medical history, physical examination, ECG, vital sign assessments, and clinical laboratory tests at Screening. Any subjects with abnormalities noted at Screening or at any time before dosing on Day 1 must be approved by the Investigator and Medical Monitor.
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- If taking concurrent medications, must be on a stable dose for at least 14 days prior to dosing and the dosing regimen should remain stable for the duration of the study;
- Prescription dry body weight of ≥75 kg and ≤135 kg at Screening;
- Must be receiving HD 3 times weekly and have been on dialysis for at least 3 months prior to Screening;
- For a minimum of 1 month before Day 1, must have stable controlled blood pressure that in the Investigator's opinion will not interfere with study conduct;
- Demonstrated adequate dialysis measurements (at least two Kt/V measurements ≥1.2 or two urea reduction ratio [URR] measurements ≥65%) during the 3 months prior to Screening
Who cannot join
- Has a concomitant disease or any medical condition that, in the opinion of the Investigator, could pose undue risk to the patient, impede completion of the study procedures, or would compromise the validity of the study measurements, including, but not limited to:
- Known or suspected history of alcohol, narcotic, or other drug abuse, or substance dependence within 12 months prior to Screening;
- Significant systolic or diastolic heart failure (eg, New York Heart Association Class IV congestive heart failure [Appendix 1]);
- Severe mental illness or cognitive impairment (eg, dementia);
- Any other relevant acute or chronic medical or neuropsychiatric condition.
- History of important drug or other allergy (except for untreated, asymptomatic seasonal allergies at time of dosing) unless deemed not clinically significant by the Investigator;
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- Use of any beverages and foods containing alcohol, quinine (tonic water), grapefruit, broccoli, Brussels sprouts, Seville oranges, pomegranate, star fruit, char-grilled meat, or caffeine/xanthine from 48 hours prior to dosing with study medication without evaluation and approval by the Investigator;
- Use of any over-the-counter (OTC) medication (including nutritional or dietary supplements, herbal preparations, or vitamins, chapparal, comfrey, germander, gin bu huan, kava, pennyroyal, skullcap, St. John's Wort, or valerian) within 7 days prior to dosing with study medication;
- Use of any new prescription medication from 14 days prior to dosing with study medication without evaluation and approval by the Investigator;
- Has been treated with any known drugs that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) enzymes (e.g., barbiturates, phenothiazines, cimetidine, carbamazepine) within 30 days prior to dosing with study medication, and that, in the Investigator's judgment, may impact subject safety or the validity of the study results;
- Positive results for human immunodeficiency virus (HIV) or hepatitis B surface antigen (HBsAg);
- Is a healthy subject with positive results for hepatitis C virus (HCV) antibody at Screening. Note: Subjects with HD who test positive for HCV antibody may be allowed to enroll at the discretion of the Principal Investigator if their liver function tests are not otherwise clinically significant;
- Has donated blood or has had an acute loss of blood (˃500 mL) during the 3 months prior to study drug administration;
- Previous administration of any [14C] labeled drug substance within 1 year of study drug administration;
- Has irregular bowel habits. "Irregular" being defined for the purpose of this study as NOT having a bowel movement at least every 2 days.)
- Has been involved in an occupation that requires monitoring for radiation exposure (eg, X-ray technician);
Trial locations and contacts
1 site in 1 country.
United States1 site
Cara Therapeutics Study Site
San Antonio, Texas, 78217
About this study
Official title: A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Metabolism of [14C] CR845 in Patients With End Stage Renal Disease on Hemodialysis and in Healthy Subjects
The objectives of this study are to evaluate the in vivo metabolite profiling and characterization of CR845 administered intravenously (IV) in patients on hemodialysis (HD) and in healthy subjects; and to determine the pharmacokinetics of radiolabeled [14C] CR845 administered as a single IV bolus in patients on HD and in healthy subjects.
Read the detailed description
This is a Phase 1, open-label, single-radiolabeled dose, non-randomized study in 6 male patients on HD and 6 healthy male subjects. The study will consist of a Screening Period, a Study Period, and an End-of-Study assessment.
- Conditions
- Hemodialysis, Healthy
- Being tested
- [14C] CR845
- Keywords
- Hemodialysis, Difelikefalin, Dialysis, CR845, CKD, ESRD (end stage renal disease)
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
[14C] CR845Drug
Subjects will receive a single dose of 230 mcg CR845 solution containing 100 microcuries [14C] CR845, administered via IV bolus (the total dose of CR845 will range from 1.7 to 3.1 mcg/kg)
| Study group | Role | What they receive |
|---|---|---|
| [14C] CR845 | Experimental | Subjects will receive a single dose of [14C] CR845 IV solution administered as an IV bolus on Day 1. Receives: Drug: [14C] CR845 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measure of the [14C] CR845 and total radioactivity (total [14C] CR845-equivalents) in plasma, urine, feces, and dialysate will be determined.
Measured: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
Extent of recovery of [14C] CR845 and radioactivity related to [14C] CR845 in plasma, urine, feces, and dialysate, as applicable, will be derived.
Measured: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
Cumulative amount of [14C] CR845 and [14C] CR845-equivalents in urine and feces over the collection period will be calculated.
Measured: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
Presence of possible CR845 metabolites will be assessed.
Measured: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
Quantitation of possible CR845 metabolites will be assessed.
Measured: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
Secondary outcomes (1)
Frequency and severity of adverse events by treatment group
Measured: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2019
- Study start17 Jan 2019
- Primary completion6 Apr 2019
- Study completion6 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HemodialysisStudies 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cara Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Frédérique Menzaghi, PhD, Study director, Cara Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03947970
- Sponsor's protocol ID
- CR845-100302
- Status last verified
- Jul 2019
- First submitted
- 9 May 2019
- Last updated
- 24 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Stark JG, Noonan PK, Spencer RH, Bhaduri S, O'Connor SJ, Menzaghi F. Pharmacokinetics, Metabolism, and Excretion of Intravenous [14C]Difelikefalin in Healthy Subjects and Subjects on Hemodialysis. Clin Pharmacokinet. 2023 Sep;62(9):1231-1241. doi: 10.1007/s40262-023-01262-2. Epub 2023 Jun 28.
PubMed 37369955
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Metabolism of [14C] CR845 in Patients With End Stage Renal Disease on Hemodialysis and in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03947970
- Acronym / sponsor ID
- CR845-100302
- Conditions
- Hemodialysis, Healthy
- Keywords
- Hemodialysis, Difelikefalin, Dialysis, CR845, CKD, ESRD (end stage renal disease)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Cara Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 17 Jan 2019 (actual)
- Primary completion
- 6 Apr 2019 (actual)
- Study completion
- 6 Apr 2019 (actual)
- First posted
- 13 May 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 objectives of this study are to evaluate the in vivo metabolite profiling and characterization of CR845 administered intravenously (IV) in patients on hemodialysis (HD) and in healthy subjects; and to determine the pharmacokinetics of radiolabeled [14C] CR845 administered as a single IV bolus in patients on HD and in healthy subjects.
Detailed description
This is a Phase 1, open-label, single-radiolabeled dose, non-randomized study in 6 male patients on HD and 6 healthy male subjects. The study will consist of a Screening Period, a Study Period, and an End-of-Study assessment.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| [14C] CR845 | Experimental | Drug: [14C] CR845Subjects will receive a single dose of [14C] CR845 IV solution administered as an IV bolus on Day 1. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Body mass index (BMI) within the range of 18 to 30 kg/m2, inclusive, and body weight not less than 75 kg;
- Vital signs at Screening must be within the following ranges and stable (measured in sitting position after at least 5 minutes' rest);
- Must be in good health as determined by past medical history, physical examination, ECG, vital sign assessments, and clinical laboratory tests at Screening. Any subjects with abnormalities noted at Screening or at any time before dosing on Day 1 must be approved by the Investigator and Medical Monitor.
- If taking concurrent medications, must be on a stable dose for at least 14 days prior to dosing and the dosing regimen should remain stable for the duration of the study;
- Prescription dry body weight of ≥75 kg and ≤135 kg at Screening;
Key exclusion criteria (16 listed)
- Has a concomitant disease or any medical condition that, in the opinion of the Investigator, could pose undue risk to the patient, impede completion of the study procedures, or would compromise the validity of the study measurements, including, but not limited to:
- History of important drug or other allergy (except for untreated, asymptomatic seasonal allergies at time of dosing) unless deemed not clinically significant by the Investigator;
- Use of any beverages and foods containing alcohol, quinine (tonic water), grapefruit, broccoli, Brussels sprouts, Seville oranges, pomegranate, star fruit, char-grilled meat, or caffeine/xanthine from 48 hours prior to dosing with study medication without evaluation and approval by the Investigator;
- Use of any over-the-counter (OTC) medication (including nutritional or dietary supplements, herbal preparations, or vitamins, chapparal, comfrey, germander, gin bu huan, kava, pennyroyal, skullcap, St. John's Wort, or valerian) within 7 days prior to dosing with study medication;
- Use of any new prescription medication from 14 days prior to dosing with study medication without evaluation and approval by the Investigator;
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 |
|---|---|---|
| [14C] CR845Subjects will receive a single dose of 230 mcg CR845 solution containing 100 microcuries [14C] CR845, administered via IV bolus (the total dose of CR845 will range from 1.7 to 3.1 mcg/kg) | Drug | [14C] CR845 |
Primary outcome
Measure of the [14C] CR845 and total radioactivity (total [14C] CR845-equivalents) in plasma, urine, feces, and dialysate will be determined.
Time frame: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
Extent of recovery of [14C] CR845 and radioactivity related to [14C] CR845 in plasma, urine, feces, and dialysate, as applicable, will be derived.
Time frame: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
Cumulative amount of [14C] CR845 and [14C] CR845-equivalents in urine and feces over the collection period will be calculated.
Time frame: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
Presence of possible CR845 metabolites will be assessed.
Time frame: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
Quantitation of possible CR845 metabolites will be assessed.
Time frame: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
1 secondary outcome
Frequency and severity of adverse events by treatment group
Time frame: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD
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 24 Jul 2019.
- Derived from this study: PubMed 37369955Stark JG, Noonan PK, Spencer RH, Bhaduri S, O'Connor SJ, Menzaghi F. Pharmacokinetics, Metabolism, and Excretion of Intravenous [14C]Difelikefalin in Healthy Subjects and Subjects on Hemodialysis. Clin Pharmacokinet. 2023 Sep;62(9):1231-1241. doi: 10.1007/s40262-023-01262-2. Epub 2023 Jun 28.
- 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.
Frédérique Menzaghi, PhD study director
Cara Therapeutics
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 [14C] CR845 in people with Hemodialysis and Healthy, run by Cara Therapeutics, Inc. at 1 site 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 11 inclusion and 16 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 24 Jul 2019. 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 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?
Measure of the [14C] CR845 and total radioactivity (total [14C] CR845-equivalents) in plasma, urine, feces, and dialysate will be determined. (time frame: Day 1 to up to 7 days post dose in healthy volunteers and Day 1 to up to 14 days post dose in patients on HD). The study lists 5 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 NCT03947970, 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 24 Jul 2019.