Hepatitis CPhase 1NCT02045966
Study to Determine the Potential DDIs When the Daclatasvir/Asunaprevir/BMS-791325 Three Drug Antiviral Combination Tablet (FDC) is Coadministered With a Cocktail of Cytochrome P450 (CYP) Probe Substrates and Transporter Probe Substrates (Digoxin and Pravastatin) in Healthy Subjects
A Phase 1 study testing Cocktail, DCV 3DAA FDC and BMS-791325 in people with Hepatitis C, run by Bristol-Myers Squibb.
Trial summary
The primary purpose of this study is to assess the effect of the Daclatasvir/Asunaprevir/BMS-791325 fixed dose combination (FDC) tablet on the pharmacokinetics of the cocktail CYP and transporter probe substrates and to assess the effect of the DCV 3DAA FDC [DCV 3DAA FDC = fixed dose combination formulation of 3… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatitis C
- What is being tested?
- Cocktail, DCV 3DAA FDC and BMS-791325
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- No sites listed yet
- Study dates
- Feb 2014to Apr 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examinations, vital sign measurements, 12-lead ECG measurements, and clinical laboratory test results
- Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive. BMI = weight (kg)/[height (m)]2
- Men and women, ages 18 to 45 years, inclusive
- Women must not be of childbearing potential, must not be breastfeeding
Who cannot join
- Any significant acute or chronic medical illness
- History of important arrhythmias including, but not limited to, ventricular fibrillation, ventricular tachycardia, complete atrioventricular (A-V) block, Wolff-Parkinson-White syndrome
- History of cardiac arrhythmias or palpitations associated with presyncope or syncope, or history of unexplained syncope
- History of heart disease
- History of prolonged QT interval or torsades de pointes (TdP)
- History of hypokalemia
Show all 16Show fewer
- Family history of sudden cardiac death at a young age, TdP, or Long QT syndrome
- History of asthma, bronchospasm, or sleep apnea
- History of rhabdomyolysis
- History of a bleeding disorder
- History of Raynaud's disease
- History of peptic ulcer disease or significant gastrointestinal bleed
- History of biliary disorders, including Gilbert's disease or Dubin-Johnson disease
- Current or recent (within 3 months of study drug administration) gastrointestinal disease
- Any major surgery within 4 weeks of study drug administration
- Any gastrointestinal surgery (including cholecystectomy) that could impact upon the absorption of study drug
About this study
Official title: Effect of a Fixed Dose Combination Formulation of Daclatasvir/Asunaprevir/BMS-791325 on the Pharmacokinetics of a Cocktail of CYP Probe Substrates (Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, and Midazolam) and Transporter Probe Substrates (Digoxin and Pravastatin) in Healthy Subjects
The primary purpose of this study is to assess the effect of the Daclatasvir/Asunaprevir/BMS-791325 fixed dose combination (FDC) tablet on the pharmacokinetics of the cocktail CYP and transporter probe substrates and to assess the effect of the DCV 3DAA FDC [DCV 3DAA FDC = fixed dose combination formulation of 3 direct-acting antivirals (3DAA) (DCV 30 mg, ASV 200 mg, and BMS-791325 75 mg)] + BMS-791325 75-mg single-agent tablet on the Pharmacokinetic (PK) of the cocktail CYP and transporter probe substrates.
Read the detailed description
IND number: 79,599 and 101,943
Primary purpose: Other: study is being conducted to investigate the potential drug-drug interactions (DDIs) when the Daclatasvir/Asunaprevir/BMS-791325 FDC formulation is coadministered with a cocktail of cytochrome P450 (CYP) probe substrates (Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, and Midazolam) and transporter probe substrates (Digoxin and Pravastatin) in healthy subjects. It is also intended to characterize the PK of Daclatasvir (DCV), Asunaprevir (ASV), BMS-791325, and its major metabolite, BMS-794712, at steady state.
- Conditions
- Hepatitis C
- Being tested
- Cocktail, DCV 3DAA FDC, BMS-791325
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CocktailDrug
Cocktail = Caffeine 200 mg, Metoprolol 50 mg, Montelukast 10 mg, Flurbiprofen 50 mg, Omeprazole 40 mg, Midazolam 5 mg, Digoxin 0.25 mg, and Pravastatin 40 mg
DCV 3DAA FDCDrug
DCV 30 mg + ASV 200 mg + BMS-791325 75 mg
BMS-791325Drug
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Cocktail + DCV 3DAA FDC + BMS-791325 | Experimental | Treatment A: Cocktail of CYP and transporter probe substrates orally as a single dose on Day 1
Treatment B: DCV 3DAA FDC tablet administered orally BID on Days 6 to 15
Treatment C: DCV 3DAA FDC tablet administered orally BID on Days 16 to 20, plus the cocktail of CYP and transporter probe substrates administered orally as a single dose on Day 16 only
Treatment D: DCV 3DAA FDC tablet plus BMS-791325 75-mg single-agent tablet administered orally BID on Days 21 to 30
Treatment E: DCV 3DAA FDC tablet plus BMS-791325 75-mg single-agent tablet administered orally BID on Days 31 to 35, plus the cocktail of CYP and transporter probe substrates administered orally as a single dose on Day 31 only Receives: Drug: Cocktail; Drug: DCV 3DAA FDC; Drug: BMS-791325 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] for each cocktail CYP and transporter probe substrate
Measured: 51 time points up to day 36
Secondary outcomes (19)
Maximum observed concentration (Cmax) for each cocktail CYP and transporter probe substrate
Measured: 51 time points up to day 36
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] for each cocktail CYP and transporter probe substrate
Measured: 51 time points up to day 36
Cmax for the measured metabolites of the cocktail CYP and transporter probe substrates
Measured: 51 time points up to day 36
AUC(0-T) for the measured metabolites of the cocktail CYP and transporter probe substrates
Measured: 51 time points up to day 36
AUC(INF) for the measured metabolites of the cocktail CYP and transporter probe substrates
Measured: 51 time points up to day 36
Time of maximum observed concentration (Tmax) for each cocktail CYP and transporter probe substrate and their metabolites
Measured: 51 time points up to day 36
Half life (T-HALF) for each cocktail CYP and transporter probe substrate and their metabolites
Measured: 51 time points up to day 36
Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) for each cocktail CYP and transporter probe substrate and their metabolites
Measured: 51 time points up to day 36
Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight [MR_AUC(0-T)] for each cocktail CYP and transporter probe substrate and their metabolites
Measured: 51 time points up to day 36
Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [MR_AUC(INF)] for each cocktail CYP and transporter probe substrate and their metabolites
Measured: 51 time points up to day 36
Apparent total body clearance (CLT/F) for each cocktail CYP and transporter probe substrate
Measured: 51 time points up to day 36
Cmax for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state
Measured: 24 time points up to day 31
Tmax for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state
Measured: 24 time points up to day 31
Concentration at 12 hours (C12) for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state
Measured: 24 time points up to day 31
Area under the concentration-time curve in one dosing interval [AUC(TAU)] for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state
Measured: 24 time points up to day 31
MR_Cmax for BMS-791325 and the metabolite, BMS-794712
Measured: 24 time points up to day 31
Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] for BMS-791325 and the metabolite, BMS-794712
Measured: 24 time points up to day 31
Trough observed plasma concentration (Ctrough) for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS-794712
Measured: 24 time points up to day 31
Safety measured by the occurrence of AEs and SAEs, abnormalities in vital sign measurements exceeding pre-defined thresholds, findings on ECG measurements and physical examinations, and marked abnormalities in clinical laboratory test results
AEs = Adverse events
SAEs = Serious Adverse events
ECG = Electrocardiogram
Measured: Up to day 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2014 (estimated)
- Study startFeb 2014
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatitis CStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02045966
- Sponsor's protocol ID
- AI443-021
- Status last verified
- Jun 2014
- First submitted
- 23 Jan 2014
- Last updated
- 17 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of a Fixed Dose Combination Formulation of Daclatasvir/Asunaprevir/BMS-791325 on the Pharmacokinetics of a Cocktail of CYP Probe Substrates (Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, and Midazolam) and Transporter Probe Substrates (Digoxin and Pravastatin) in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02045966
- Acronym / sponsor ID
- AI443-021
- Conditions
- Hepatitis C
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 27 Jan 2014 (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 primary purpose of this study is to assess the effect of the Daclatasvir/Asunaprevir/BMS-791325 fixed dose combination (FDC) tablet on the pharmacokinetics of the cocktail CYP and transporter probe substrates and to assess the effect of the DCV 3DAA FDC [DCV 3DAA FDC = fixed dose combination formulation of 3 direct-acting antivirals (3DAA) (DCV 30 mg, ASV 200 mg, and BMS-791325 75 mg)] + BMS-791325 75-mg single-agent tablet on the Pharmacokinetic (PK) of the cocktail CYP and transporter probe substrates.
Detailed description
IND number: 79,599 and 101,943
Primary purpose: Other: study is being conducted to investigate the potential drug-drug interactions (DDIs) when the Daclatasvir/Asunaprevir/BMS-791325 FDC formulation is coadministered with a cocktail of cytochrome P450 (CYP) probe substrates (Caffeine, Metoprolol, Montelukast, Flurbiprofen, Omeprazole, and Midazolam) and transporter probe substrates (Digoxin and Pravastatin) in healthy subjects. It is also intended to characterize the PK of Daclatasvir (DCV), Asunaprevir (ASV), BMS-791325, and its major metabolite, BMS-794712, at steady state.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Cocktail + DCV 3DAA FDC + BMS-791325 | Experimental | Drug: Cocktail, Drug: DCV 3DAA FDC, Drug: BMS-791325Treatment A: Cocktail of CYP and transporter probe substrates orally as a single dose on Day 1 Treatment B: DCV 3DAA FDC tablet administered orally BID on Days 6 to 15 Treatment C: DCV 3DAA FDC tablet administered orally BID on Days 16 to 20, plus the cocktail of CYP and transporter probe substrates administered orally as a single dose on Day 16 only Treatment D: DCV 3DAA FDC tablet plus BMS-791325 75-mg single-agent tablet administered orally BID on Days 21 to 30 Treatment E: DCV 3DAA FDC tablet plus BMS-791325 75-mg single-agent tablet administered orally BID on Days 31 to 35, plus the cocktail of CYP and transporter probe substrates administered orally as a single dose on Day 31 only |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy subjects as determined by no clinically significant deviation from normal in medical history, physical examinations, vital sign measurements, 12-lead ECG measurements, and clinical laboratory test results
- Body mass index (BMI) of 18.0 to 32.0 kg/m2, inclusive. BMI = weight (kg)/[height (m)]2
- Men and women, ages 18 to 45 years, inclusive
- Women must not be of childbearing potential, must not be breastfeeding
Key exclusion criteria (16 listed)
- Any significant acute or chronic medical illness
- History of important arrhythmias including, but not limited to, ventricular fibrillation, ventricular tachycardia, complete atrioventricular (A-V) block, Wolff-Parkinson-White syndrome
- History of cardiac arrhythmias or palpitations associated with presyncope or syncope, or history of unexplained syncope
- History of heart disease
- History of prolonged QT interval or torsades de pointes (TdP)
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 |
|---|---|---|
| CocktailCocktail = Caffeine 200 mg, Metoprolol 50 mg, Montelukast 10 mg, Flurbiprofen 50 mg, Omeprazole 40 mg, Midazolam 5 mg, Digoxin 0.25 mg, and Pravastatin 40 mg | Drug | Arm 1: Cocktail + DCV 3DAA FDC + BMS-791325 |
| DCV 3DAA FDCDCV 30 mg + ASV 200 mg + BMS-791325 75 mg | Drug | Arm 1: Cocktail + DCV 3DAA FDC + BMS-791325 |
| BMS-791325 | Drug | Arm 1: Cocktail + DCV 3DAA FDC + BMS-791325 |
Primary outcome
Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] for each cocktail CYP and transporter probe substrate
Time frame: 51 time points up to day 36
19 secondary outcomes
Maximum observed concentration (Cmax) for each cocktail CYP and transporter probe substrate
Time frame: 51 time points up to day 36
Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] for each cocktail CYP and transporter probe substrate
Time frame: 51 time points up to day 36
Cmax for the measured metabolites of the cocktail CYP and transporter probe substrates
Time frame: 51 time points up to day 36
AUC(0-T) for the measured metabolites of the cocktail CYP and transporter probe substrates
Time frame: 51 time points up to day 36
AUC(INF) for the measured metabolites of the cocktail CYP and transporter probe substrates
Time frame: 51 time points up to day 36
Time of maximum observed concentration (Tmax) for each cocktail CYP and transporter probe substrate and their metabolites
Time frame: 51 time points up to day 36
Half life (T-HALF) for each cocktail CYP and transporter probe substrate and their metabolites
Time frame: 51 time points up to day 36
Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) for each cocktail CYP and transporter probe substrate and their metabolites
Time frame: 51 time points up to day 36
Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight [MR_AUC(0-T)] for each cocktail CYP and transporter probe substrate and their metabolites
Time frame: 51 time points up to day 36
Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight [MR_AUC(INF)] for each cocktail CYP and transporter probe substrate and their metabolites
Time frame: 51 time points up to day 36
Apparent total body clearance (CLT/F) for each cocktail CYP and transporter probe substrate
Time frame: 51 time points up to day 36
Cmax for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state
Time frame: 24 time points up to day 31
Tmax for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state
Time frame: 24 time points up to day 31
Concentration at 12 hours (C12) for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state
Time frame: 24 time points up to day 31
Area under the concentration-time curve in one dosing interval [AUC(TAU)] for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS- 794712 at steady state
Time frame: 24 time points up to day 31
MR_Cmax for BMS-791325 and the metabolite, BMS-794712
Time frame: 24 time points up to day 31
Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] for BMS-791325 and the metabolite, BMS-794712
Time frame: 24 time points up to day 31
Trough observed plasma concentration (Ctrough) for Daclatasvir, Asunaprevir, BMS-791325, and the metabolite, BMS-794712
Time frame: 24 time points up to day 31
Safety measured by the occurrence of AEs and SAEs, abnormalities in vital sign measurements exceeding pre-defined thresholds, findings on ECG measurements and physical examinations, and marked abnormalities in clinical laboratory test results
Time frame: Up to day 36
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 17 Jun 2014.
Related trials for Hepatitis C
RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Not yet recruitingObservational study
Elimination of Hepatitis C Virus Among Users of Substances
Hepatitis C in Substance Users
Not yet recruiting
Clinical Study to Evaluate the Performance of the INSTI® HCV Antibody Test for CLIA-Waived Use
HCV Infection
Not yet recruiting
Study to Evaluate the Performance of the INSTI® HCV Antibody Test for Point-of-Care Use in Individuals at Risk for HCV Infection or Presenting With Signs or Symptoms of HCV Infection
HCV Infection
Active, not recruitingPhase 4
People With CHC Who Achieved a Sustained Virological Response Following Therapy With Direct Acting Antiviral Agents
Diabetes Mellitus, Hepatitis C, Chronic
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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cocktail, DCV 3DAA FDC and BMS-791325 in people with Hepatitis C, run by Bristol-Myers Squibb.
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 4 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 17 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
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?
Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] for each cocktail CYP and transporter probe substrate (time frame: 51 time points up to day 36). 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 17 Jun 2014.