Chronic Hepatitis CPhase 1/2NCT00546715
A Single Ascending Dose Study of Daclatasvir (BMS-790052) in Hepatitis C Virus Infected Subjects
A Phase 1/2 study testing Daclatasvir in people with Chronic Hepatitis C, run by Bristol-Myers Squibb at 7 sites in United States.
Trial summary
The primary purpose of this study is to evaluate the safety profile and tolerability of single oral doses of daclatasvir in subjects with chronic hepatitis C infection Read more about this study
- Who is it for?
- Ages 18 to 49 years
- Conditions the study is for
- Chronic Hepatitis C
- What is being tested?
- Daclatasvir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 95 participants
- Where
- 7 sitesUnited States
- Study dates
- Nov 2007to May 2008
- Phase
- Phase 1/2
- 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 49 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Chronically infected with hepatitis C virus genotype 1
- Treatment naive or treatment non-responders or treatment intolerant; and not co-infected with HIV or hepatitis B virus
- Hepatitis C virus RNA viral load of ≥ 10*5* IU/mL
- BMI 18 to 35 kg/m²
Who cannot join
- Any significant acute or chronic medical illness which is not stable or is not controlled with medication and not consistent with hepatitis C virus infection
- Major surgery within 4 weeks of study drug administration and any gastrointestinal surgery that could impact the absorption of study drug
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Advanced Clinical Research Institute
Anaheim, California, 92801
Parexel International Corporation
Baltimore, Maryland, 21225
University Of Virginia Digestive Health Center Of Excellence
Charlottesville, Virginia, 22908
Bristol-Myers Squibb Clinical Pharmacology Unit
Hamilton, New Jersey, 08690
Orlando Clinical Research Center
Orlando, Florida, 32809
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
Mayo Clinic
Rochester, Minnesota, 55905
About this study
Official title: Placebo-Controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of BMS-790052 in Subjects Chronically Infected With Hepatitis C Virus Genotype 1
The primary purpose of this study is to evaluate the safety profile and tolerability of single oral doses of daclatasvir in subjects with chronic hepatitis C infection
- Conditions
- Chronic Hepatitis C
- Being tested
- Daclatasvir, Placebo
- Medical subject headings
- Hepatitis C, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DaclatasvirDrug
Oral Solution, Oral, Single Dose
PlaceboDrug
Oral Solution, Oral, Single Dose
| Study group | Role | What they receive |
|---|---|---|
| Dose Panel A | Active comparator | Daclatasvir - 1 mg
Placebo - 0 mg Receives: Drug: Daclatasvir; Drug: Placebo |
| Dose Panel B | Active comparator | Daclatasvir - 10 mg
Placebo - 0 mg Receives: Drug: Daclatasvir; Drug: Placebo |
| Dose Panel C | Active comparator | Daclatasvir - 100 mg
Placebo - 0 mg Receives: Drug: Daclatasvir; Drug: Placebo |
| Dose Panel D | Active comparator | Daclatasvir - 0.5 - 200 mg (to be determined)
Placebo - 0 mg Receives: Drug: Daclatasvir; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died
AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding) or disease which either occurs during study, whether or not related to the study drug. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Measured: Day 1 up to Day 7 for non-SAEs and Day 1 to 30 days after study discontinuation for SAEs
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Measurements and Physical Examination Findings
Participants were assessed by investigator for any clinically significant changes in vital parameters like body temperature, respiratory rate, blood pressure, heart rate and weight. The assessment was performed by a calibrated sphygmomanometer and thermometer for blood pressure and temperature, respectively. Blood pressure and heart rate were measured after at least 5 minutes quiet seating of the subject. Weight was measured at the discharge. The criteria for clinically significant change was as per the investigators discretion.
Measured: Day 1 up to Day 7 or Discharge
Number of Participants With Marked Abnormalities in Laboratory Findings
Laboratory marked abnormalities were defined as Hematocrit (low) as <0.85*pre-treatment value, Leukocytes (low) as <0.9*lower limit of normal, Aspartate Aminotransferase (high) as >1.25*upper limit of normal, Creatinine (high) as >1.33*pre-treatment value, Bicarbonate (high) as >1.2*upper limit of normal, Total Protein (high) as >1.1*upper limit of normal, Creatinine Kinase (high) as >1.5*upper limit of normal, Blood in Urine (high) as ≥ 2*upper limit of normal. Participants were fasted for at least 10 hours prior to the collection of blood specimens for clinical laboratory tests.
Measured: Day 1 up to Day 7
Secondary outcomes (10)
Maximum Observed Plasma Concentration (Cmax) and Observed Plasma Concentration at 12 Hours (C-12) and 24 Hours (C-24)
Maximum observed plasma concentration following drug administration from the raw plasma concentration-time data. C-12 and C-24 were defined as observed plasma concentration of daclatasvir at 12 hours and 24 hours, respectively. The plasma samples were analyzed for daclatasvir using a validated liquid chromatography-tandem mass spectrometric assay.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-T]), Area Under the Plasma Concentration-time Curve From Time Zero (AUC[INF]) Extrapolated to Infinite Time
Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. It was calculated as the sum of linear trapezoids using non-compartmental analysis. Area under the plasma concentration-time curve from time zero extrapolated to infinite time was estimated as sum of AUC(0-T) and the extrapolated area, computed by the quotient of the last observable concentration and λ, where λ was the slopes of the terminal phases of the plasma concentration-time profiles. The plasma samples were analyzed for daclatasvir using a validated liquid chromatography-tandem mass spectrometric assay.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1
Time to Reach Maximum Plasma Concentration (Tmax)
Tmax was defined as the time required to reach maximum observed plasma concentration. The plasma samples were analyzed for daclatasvir using a validated liquid chromatography-tandem mass spectrometric assay.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1
Plasma Half-life (T-half)
Plasma half-life was defined as the time required for one half of the total amount of administered drug eliminated from the body. The plasma samples were analyzed for daclatasvir using a validated liquid chromatography-tandem mass spectrometric assay.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1
Apparent Total Body Clearance (CLT/F)
Apparent total body clearance (CLT/F) was calculated as Dose/AUC(INF), where CLT was the clearance of the drug and F was the absolute oral bioavailability. The plasma samples were analyzed for daclatasvir using a validated liquid chromatography-tandem mass spectrometric assay.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1
Decline From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
The Roche TaqMan HCV quantitative assay was used for analysis with detection limit of 10 IU/mL. Positive value indicated reduction from baseline in HCV RNA while negative value indicated an increase from baseline in HCV RNA. Baseline HCV RNA was defined as the pre-dose value on Day 1 log10 HCV RNA.
Measured: Pre-dose, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 144 hours post-dose on Day 1
Time to Reach Maximum Decline in Plasma Hepatitis C Virus RNA Levels From Baseline
Participants were assessed for time to reach maximum decrease in log10 hepatitis C virus RNA level. Baseline HCV RNA was defined as the pre-dose value on Day 1 log10 HCV RNA.
Measured: Pre-dose, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 144 hours post-dose on Day 1
Change From Baseline in Heart Rate to Day 7 or Discharge
Changes in heart rate from baseline were measured after the participants were supine for at least 5 minutes. Baseline was defined as the Day 1 pre-dose measurement. The normal heart rate lies between 60-90 beats per minute (bpm), below 60 bpm and above 90 bpm were considered as bradycardia and tachycardia, respectively.
Measured: Baseline (Day 1), Day 7 or Discharge
Change From Baseline in Electrocardiogram (ECG) Parameters (PR, QRS, QT, and QTc Intervals) to Day 7 or Discharge
The ECG was recorded after the participant was in a supine position for at least 5 minutes. Baseline was defined as the Day 1 pre-dose measurement. The PR interval was defined as the beginning of the P wave to the beginning of the QRS complex, and represents the time taken by electrical impulse to travel from the sinus node through the atrioventricular (AV) node. The QRS complex represented the rapid depolarization of the right and left ventricles. The QT interval was defined as the time from the start of the Q wave to the end of the T wave, and represents the time taken for ventricular depolarization and repolarization. QTc was defined as corrected QT interval at a heart rate of 60 bpm. QTc was estimated using Bazett's formula and Fredericia's formula.
Measured: Baseline (Day 1), Day 7 or Discharge
Change From Baseline in Blood Pressure to Day 7 or Discharge
Changes in blood pressure from baseline were measured after the participants were supine for at least 5 minutes. Baseline was defined as the Day 1 pre-dose measurement.
Measured: Baseline (Day 1), Day 7 or Discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2007 (estimated)
- Study startNov 2007
- Primary completionMay 2008
- Study completionMay 2008
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.
- Other trials for Chronic 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 95 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
- NCT00546715
- Sponsor's protocol ID
- AI444-002
- Status last verified
- Oct 2015
- First submitted
- 17 Oct 2007
- Last updated
- 18 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Placebo-Controlled Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of BMS-790052 in Subjects Chronically Infected With Hepatitis C Virus Genotype 1
- ClinicalTrials.gov ID
- NCT00546715
- Acronym / sponsor ID
- AI444-002
- Conditions
- Chronic Hepatitis C
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 95 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Nov 2007
- Primary completion
- May 2008 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 19 Oct 2007 (estimated)
- Results
- Posted 10 Sep 2015
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 evaluate the safety profile and tolerability of single oral doses of daclatasvir in subjects with chronic hepatitis C infection
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Panel A | Active comparator | Drug: Daclatasvir, Drug: PlaceboDaclatasvir - 1 mg Placebo - 0 mg |
| Dose Panel B | Active comparator | Drug: Daclatasvir, Drug: PlaceboDaclatasvir - 10 mg Placebo - 0 mg |
| Dose Panel C | Active comparator | Drug: Daclatasvir, Drug: PlaceboDaclatasvir - 100 mg Placebo - 0 mg |
| Dose Panel D | Active comparator | Drug: Daclatasvir, Drug: PlaceboDaclatasvir - 0.5 - 200 mg (to be determined) Placebo - 0 mg |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Chronically infected with hepatitis C virus genotype 1
- Treatment naive or treatment non-responders or treatment intolerant; and not co-infected with HIV or hepatitis B virus
- Hepatitis C virus RNA viral load of ≥ 10*5* IU/mL
- BMI 18 to 35 kg/m²
Key exclusion criteria (2 listed)
- Any significant acute or chronic medical illness which is not stable or is not controlled with medication and not consistent with hepatitis C virus infection
- Major surgery within 4 weeks of study drug administration and any gastrointestinal surgery that could impact the absorption of study drug
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 |
|---|---|---|
| DaclatasvirOral Solution, Oral, Single Dose | Drug | Dose Panel A, Dose Panel B, Dose Panel C, Dose Panel D |
| PlaceboOral Solution, Oral, Single Dose | Drug | Dose Panel A, Dose Panel B, Dose Panel C, Dose Panel D |
Primary outcome
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died
Time frame: Day 1 up to Day 7 for non-SAEs and Day 1 to 30 days after study discontinuation for SAEs
AEs were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding) or disease which either occurs during study, whether or not related to the study drug. SAEs were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards.
Number of Participants With Clinically Significant Change From Baseline in Vital Sign Measurements and Physical Examination Findings
Time frame: Day 1 up to Day 7 or Discharge
Participants were assessed by investigator for any clinically significant changes in vital parameters like body temperature, respiratory rate, blood pressure, heart rate and weight. The assessment was performed by a calibrated sphygmomanometer and thermometer for blood pressure and temperature, respectively. Blood pressure and heart rate were measured after at least 5 minutes quiet seating of the subject. Weight was measured at the discharge. The criteria for clinically significant change was as per the investigators discretion.
Number of Participants With Marked Abnormalities in Laboratory Findings
Time frame: Day 1 up to Day 7
Laboratory marked abnormalities were defined as Hematocrit (low) as <0.85*pre-treatment value, Leukocytes (low) as <0.9*lower limit of normal, Aspartate Aminotransferase (high) as >1.25*upper limit of normal, Creatinine (high) as >1.33*pre-treatment value, Bicarbonate (high) as >1.2*upper limit of normal, Total Protein (high) as >1.1*upper limit of normal, Creatinine Kinase (high) as >1.5*upper limit of normal, Blood in Urine (high) as ≥ 2*upper limit of normal. Participants were fasted for at least 10 hours prior to the collection of blood specimens for clinical laboratory tests.
10 secondary outcomes
Maximum Observed Plasma Concentration (Cmax) and Observed Plasma Concentration at 12 Hours (C-12) and 24 Hours (C-24)
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-T]), Area Under the Plasma Concentration-time Curve From Time Zero (AUC[INF]) Extrapolated to Infinite Time
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1
Time to Reach Maximum Plasma Concentration (Tmax)
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1
Plasma Half-life (T-half)
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1
Apparent Total Body Clearance (CLT/F)
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 48 and 72 hours post-dosing on Day 1
Decline From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA)
Time frame: Pre-dose, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 144 hours post-dose on Day 1
Time to Reach Maximum Decline in Plasma Hepatitis C Virus RNA Levels From Baseline
Time frame: Pre-dose, 2, 4, 6, 8, 12, 16, 24, 36, 48, 72 and 144 hours post-dose on Day 1
Change From Baseline in Heart Rate to Day 7 or Discharge
Time frame: Baseline (Day 1), Day 7 or Discharge
Change From Baseline in Electrocardiogram (ECG) Parameters (PR, QRS, QT, and QTc Intervals) to Day 7 or Discharge
Time frame: Baseline (Day 1), Day 7 or Discharge
Change From Baseline in Blood Pressure to Day 7 or Discharge
Time frame: Baseline (Day 1), Day 7 or Discharge
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Daclatasvir in people with Chronic Hepatitis C, run by Bristol-Myers Squibb at 7 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 4 inclusion and 2 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 18 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 10 Sep 2015). 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?
Number of Participants With Serious Adverse Events (SAEs), Discontinuations Due to Adverse Events (AEs) and Who Died (time frame: Day 1 up to Day 7 for non-SAEs and Day 1 to 30 days after study discontinuation for SAEs). 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?
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 18 Nov 2015.