Renal ImpairmentPhase 1NCT02508740
Single Oral Dose of Bevenopran in Patients With Varying Degrees of Renal Impairment
A Phase 1 study testing bevenopran in people with Renal Impairment, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 2 sites in United States.
Trial summary
The purpose of this study is to characterize the effect of renal function on the PK of a 0.25 mg single oral dose of bevenopran in humans and to assess the safety and tolerability of bevenopran in patients with varying degrees of renal impairment and in healthy subjects. Read more about this study
- Who is it for?
- Ages 18 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Renal Impairment
- What is being tested?
- bevenopran
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 2013to Dec 2013
- 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 18 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy (other than renal impairment) male or female subjects 18 to 80 years of age, inclusive;
- Body mass index (BMI) within the range of 18.0 to 45.0 kg/m2, inclusive, and a minimum weight of at least 50.0 kg at Screening;
- Patients with renal impairment are to have mild, moderate, or severe renal impairment, or ESRD patients requiring dialysis. ESRD patients requiring dialysis should have been receiving dialysis on a 3 times/week schedule for at least 3 months preceding the initial dose in this study;
- For healthy subjects and non-dialysis patients: If female, subject is not pregnant (as confirmed by pregnancy test at Screening and Day -1) and not planning to become pregnant within 30 days of last study drug administration, non-lactating, and is either:
- Not of child bearing potential, defined as postmenopausal for at least one year or <60 years old with no menses for >1 year confirmed by follicle stimulating hormone (FSH), or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;
- Of childbearing potential and utilizes one of the following: abstinence, hormonal contraceptives from at least 3 months prior to Screening, intrauterine device (IUD), double barrier method (acceptable double barrier methods are male condom plus sponge/diaphragm/hormones/IUD, condom plus spermicide is not acceptable), in combination with an additional method of contraception for their male partners. Subjects must be willing to practice these methods for the duration of the trial and for at least 30 days after last study drug administration. For dialysis patients (Group E): If female, must not be of child bearing potential, defined as postmenopausal for at least one year or <60 years old with no menses for >1 year confirmed by follicle stimulating hormone (FSH) or subject medical history, or surgically sterile (ie, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy);
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- Male subjects with female sexual partners, must be using and willing to continue using medically acceptable forms of contraception (abstinence, vasectomy, or male condom for subjects plus an additional method of contraception for their female partners) from Screening and for at least 30 days after the last study drug administration;
- Non-smoker for at least 1 year prior to Screening, as determined by self-reported history;
- Able to speak, read, and understand English sufficiently to understand the nature of the study, to provide written informed consent, prior to the initiation of any protocol-specific procedures;
- Must be willing and able to abide by all study requirements and restrictions;
- Must be willing to abstain from the following foods from 1 week prior to first study drug administration until the end of the study: grapefruit, pomegranate, pomelo and star fruit juice/products, as well as foods containing poppy seeds, Seville oranges, and/or drinks or food containing quinine (ie, tonic water);
- Must be willing to refrain from consuming more than 450 mg of caffeine per day (equivalent to approximately 2.5 cups of drip coffee);
- Must be willing to refrain from strenuous physical activity for 48 hours prior to each study visit and during inpatient stays at the research site;
- Must be willing to abstain from blood donation during the study and for 30 days after completion of study or early termination.
Who cannot join
- For healthy subjects: history or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, including clinically significant anemia, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results; For renally impaired patients: as above, except renal insufficiency and other related stable medical conditions within the renally impaired subject population (eg, hypertension, diabetes, which should be stable for at least 3 months preceding the initial dose of study drug in this study) are allowed;
- Clinically significant abnormalities on physical examination, medical history, 12-lead electrocardiogram (ECG), vital signs, or laboratory values, as judged by the investigator or designee. Subjects with renal impairment should have clinical laboratory values consistent with their disease and approved by the investigator;
- QTcF > 480 ms for renally impaired patients and > 450 ms for healthy subjects;
- Surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the study drug, as judged by the investigator or designee;
- Evidence of clinically significant hepatic (all subjects) or renal (healthy subjects only) impairment including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 × upper limit of normal (ULN) or bilirubin > 1 × ULN;
- Hemoglobin <9 g/dL, unless not considered clinically significant in the opinion of the investigator;
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- History of severe allergic reaction (including anaphylaxis) to any food, medication, or bee sting or previous status asthmaticus;
- Patients with renal impairment who are not on a chronic stable drug regimen, defined as starting a new drug or changing dosage within 14 days prior to administration of study drug, except for drugs that manage the hemodialysis;
- Patients with fluctuating or rapidly deteriorating renal function. Assessment of the stability of the patient's renal function will be determined by the investigator;
- Patient has a functioning renal transplant (patient may be included in the study if he or she had a failed renal transplant and is not taking immunosuppressants);
- Current self-reported drug or alcohol dependence (excluding caffeine), including subjects who have been in a drug rehabilitation program in the 6 months prior to Screening;
- Use of any prescription drug, over the counter (OTC) medication or supplement, including p-gp inhibitors, within the 14 days (30 days for p-gp inducers) prior to dosing until study completion/early termination, unless therapeutic (renal patients) or approved by the medical monitor;
- Use of any opioid therapy within 14 days or 5 half-lives of the specific opioid drug (whichever is longer) before the scheduled administration of study medication. Subjects using opioids to help manage their disease will need to wash out for 5 half-lives.
- Positive drug screen upon presentation at Screening or upon Check-in at admission;
- Positive breath alcohol test upon presentation at Screening or upon Check-in at admission;
- History of allergy or hypersensitivity to bevenopran, or related drugs;
- For healthy subjects: positive for Hepatitis B, Hepatitis C, or human immunodeficiency virus (HIV); For renally impaired patients: positive for Hepatitis B or HIV. Patients with Hepatitis C with acceptable liver function tests (as judged by the investigator or designee) may be included;
- Donated or lost more than 450 mL of blood (one unit) in the 60 days preceding (first) study medication administration;
- Has received an investigational product in a clinical trial within 30 days or 5 half-lives, whichever is longer, prior to first drug administration or is concurrently enrolled in any other type of medical research, judged not to be scientifically or medically compatible with this study; An employee of the sponsor or research site personnel directly affiliated with this study or their immediate family members defined as a spouse, parent, child or sibling, whether biological or legally adopted;
- 21. A subject who, in the opinion of the investigator or designee, is not considered to be suitable and is unlikely to comply with the study restrictions or study protocol for any reason.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
DaVita Clinical Research: Denver Clinical Research Unit
Lakewood, Colorado, 80228
DaVita Clinical Research: Minneapolis Research Unit
Minneapolis, Minnesota, 55404
About this study
Official title: Phase 1, Non-Randomized, Parallel-Group, Open-Label Study to Characterize the Pharmacokinetics of a Single Oral Dose of Bevenopran in Patients With Varying Degrees of Renal Impairment Compared to Healthy Subjects
The purpose of this study is to characterize the effect of renal function on the PK of a 0.25 mg single oral dose of bevenopran in humans and to assess the safety and tolerability of bevenopran in patients with varying degrees of renal impairment and in healthy subjects.
Read the detailed description
The current Food and Drug Administration (FDA) draft guidance for renal impairment studies advises performance of a PK study in patients with renal impairment for medications primarily excreted in urine and also for medications primarily metabolized or secreted in bile. The major routes of excretion of bevenopran in animals were identified as hepatobiliary and renal. In addition, preliminary findings show >40% of an oral bevenopran dose is eliminated unchanged in urine over a 48-72 hour period post-dose.
This is a Phase 1, non-randomized, parallel group, open-label study to characterize the effect of renal function on the PK of bevenopran in 1 or more study centers. At screening, eligible subjects will be enrolled and assigned to 1 of 5 parallel study groups of approximately 8 to 12 subjects each based on the classification of the renal function using estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study, as presented in the FDA guidance on renal impairment studies. There are 5 study groups based on eGFRs.
- Conditions
- Renal Impairment
- Being tested
- bevenopran
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevenopranDrug
Also called 5945
Single oral dose
| Study group | Role | What they receive |
|---|---|---|
| normal renal function | Experimental | Healthy subjects with normal renal function (Stage 1, >90 mL/min) will receive a single oral dose of 0.25 mg bevenopran. Receives: Drug: bevenopran |
| mild renal impairment | Experimental | Patients with mild renal impairment (Stage 2, 60-89 mL/min) will receive a single oral dose of 0.25 mg bevenopran. Receives: Drug: bevenopran |
| moderate renal impairment | Experimental | Patients with moderate renal impairment (Stage 3, 30-59 mL/min) will receive a single oral dose of 0.25 mg bevenopran. Receives: Drug: bevenopran |
| severe renal impairment | Experimental | Patients with severe renal impairment (Stage 4, <30 mL/min) will receive a single oral dose of 0.25 mg bevenopran. Receives: Drug: bevenopran |
| End Stage Renal Disease (ESRD) | Experimental | Patients with End Stage Renal Disease (ESRD) receiving dialysis for at least 3 months preceding the initial dose in this study (Stage 5) will participate in 2 treatment periods and will receive a single oral dose of 0.25 mg bevenopran at 3 hours after completion of the last hemodialysis session of the week in Period 1 and a single oral dose of 0.25 mg bevenopran at 3 hours before initiation of the last hemodialysis session of the week in Period 2 Receives: Drug: bevenopran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma concentrations of a 0.25 mg single oral dose of bevenopran
To characterize the effect of renal function on the PK of a 0.25 mg single oral dose of bevenopran in humans
Measured: pre-dose, 0-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120 h post-dose
Secondary outcomes (1)
Number of adverse events for subjects enrolled
To assess the safety and tolerability of bevenopran in patients with varying degrees of renal impairment and in healthy subjects.
Measured: 6 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2015 (estimated)
- Study startSep 2013
- Primary completionDec 2013
- Study completionDec 2013
Why it stopped: Development of compound has been put on hold.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal ImpairmentStudies 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02508740
- Sponsor's protocol ID
- 5945-REN-13-03
- Status last verified
- Jul 2015
- First submitted
- 22 Jul 2015
- Last updated
- 27 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Non-Randomized, Parallel-Group, Open-Label Study to Characterize the Pharmacokinetics of a Single Oral Dose of Bevenopran in Patients With Varying Degrees of Renal Impairment Compared to Healthy Subjects
- ClinicalTrials.gov ID
- NCT02508740
- Acronym / sponsor ID
- 5945-REN-13-03
- Conditions
- Renal Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Development of compound has been put on hold.
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
- Collaborators
- Syneos Health
- Study start
- Sep 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 27 Jul 2015 (estimated)
- 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 purpose of this study is to characterize the effect of renal function on the PK of a 0.25 mg single oral dose of bevenopran in humans and to assess the safety and tolerability of bevenopran in patients with varying degrees of renal impairment and in healthy subjects.
Detailed description
The current Food and Drug Administration (FDA) draft guidance for renal impairment studies advises performance of a PK study in patients with renal impairment for medications primarily excreted in urine and also for medications primarily metabolized or secreted in bile. The major routes of excretion of bevenopran in animals were identified as hepatobiliary and renal. In addition, preliminary findings show >40% of an oral bevenopran dose is eliminated unchanged in urine over a 48-72 hour period post-dose.
This is a Phase 1, non-randomized, parallel group, open-label study to characterize the effect of renal function on the PK of bevenopran in 1 or more study centers. At screening, eligible subjects will be enrolled and assigned to 1 of 5 parallel study groups of approximately 8 to 12 subjects each based on the classification of the renal function using estimated glomerular filtration rate (eGFR) from the Modification of Diet in Renal Disease (MDRD) Study, as presented in the FDA guidance on renal impairment studies. There are 5 study groups based on eGFRs.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| normal renal function | Experimental | Drug: bevenopranHealthy subjects with normal renal function (Stage 1, >90 mL/min) will receive a single oral dose of 0.25 mg bevenopran. |
| mild renal impairment | Experimental | Drug: bevenopranPatients with mild renal impairment (Stage 2, 60-89 mL/min) will receive a single oral dose of 0.25 mg bevenopran. |
| moderate renal impairment | Experimental | Drug: bevenopranPatients with moderate renal impairment (Stage 3, 30-59 mL/min) will receive a single oral dose of 0.25 mg bevenopran. |
| severe renal impairment | Experimental | Drug: bevenopranPatients with severe renal impairment (Stage 4, <30 mL/min) will receive a single oral dose of 0.25 mg bevenopran. |
| End Stage Renal Disease (ESRD) | Experimental | Drug: bevenopranPatients with End Stage Renal Disease (ESRD) receiving dialysis for at least 3 months preceding the initial dose in this study (Stage 5) will participate in 2 treatment periods and will receive a single oral dose of 0.25 mg bevenopran at 3 hours after completion of the last hemodialysis session of the week in Period 1 and a single oral dose of 0.25 mg bevenopran at 3 hours before initiation of the last hemodialysis session of the week in Period 2 |
Who may qualify
- Ages
- 18 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Healthy (other than renal impairment) male or female subjects 18 to 80 years of age, inclusive;
- Body mass index (BMI) within the range of 18.0 to 45.0 kg/m2, inclusive, and a minimum weight of at least 50.0 kg at Screening;
- Patients with renal impairment are to have mild, moderate, or severe renal impairment, or ESRD patients requiring dialysis. ESRD patients requiring dialysis should have been receiving dialysis on a 3 times/week schedule for at least 3 months preceding the initial dose in this study;
- For healthy subjects and non-dialysis patients: If female, subject is not pregnant (as confirmed by pregnancy test at Screening and Day -1) and not planning to become pregnant within 30 days of last study drug administration, non-lactating, and is either:
- Male subjects with female sexual partners, must be using and willing to continue using medically acceptable forms of contraception (abstinence, vasectomy, or male condom for subjects plus an additional method of contraception for their female partners) from Screening and for at least 30 days after the last study drug administration;
Key exclusion criteria (20 listed)
- For healthy subjects: history or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, including clinically significant anemia, which in the opinion of the investigator would jeopardize the safety of the subject or the validity of the study results; For renally impaired patients: as above, except renal insufficiency and other related stable medical conditions within the renally impaired subject population (eg, hypertension, diabetes, which should be stable for at least 3 months preceding the initial dose of study drug in this study) are allowed;
- Clinically significant abnormalities on physical examination, medical history, 12-lead electrocardiogram (ECG), vital signs, or laboratory values, as judged by the investigator or designee. Subjects with renal impairment should have clinical laboratory values consistent with their disease and approved by the investigator;
- QTcF > 480 ms for renally impaired patients and > 450 ms for healthy subjects;
- Surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the study drug, as judged by the investigator or designee;
- Evidence of clinically significant hepatic (all subjects) or renal (healthy subjects only) impairment including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 1.5 × upper limit of normal (ULN) or bilirubin > 1 × ULN;
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 |
|---|---|---|
| bevenopranAlso: 5945Single oral dose | Drug | End Stage Renal Disease (ESRD), mild renal impairment, moderate renal impairment, normal renal function, severe renal impairment |
Primary outcome
Plasma concentrations of a 0.25 mg single oral dose of bevenopran
Time frame: pre-dose, 0-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120 h post-dose
To characterize the effect of renal function on the PK of a 0.25 mg single oral dose of bevenopran in humans
1 secondary outcome
Number of adverse events for subjects enrolled
Time frame: 6 days
Results and safety
The study was stopped early (reason given: Development of compound has been put on hold.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2015.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 bevenopran in people with Renal Impairment, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) 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 14 inclusion and 20 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: stopped early, as of the sponsor's last update on 27 Jul 2015. 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 was stopped early (reason given: Development of compound has been put on hold.). Results are not available in the source record.
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?
Plasma concentrations of a 0.25 mg single oral dose of bevenopran (time frame: pre-dose, 0-8, 8-12, 12-24, 24-48, 48-72, 72-96, 96-120 h post-dose). 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 27 Jul 2015; AzTrials last refreshed its copy on 8 Nov 2026.