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A Single Ascending Dose Study of Daclatasvir (BMS-790052) in Hepatitis C Virus Infected Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00546715
Recruitment Status : Completed
First Posted : October 19, 2007
Results First Posted : September 10, 2015
Last Update Posted : November 18, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE October 17, 2007
First Posted Date  ICMJE October 19, 2007
Results First Submitted Date  ICMJE August 10, 2015
Results First Posted Date  ICMJE September 10, 2015
Last Update Posted Date November 18, 2015
Study Start Date  ICMJE November 2007
Actual Primary Completion Date May 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 20, 2015)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 17, 2007)
Safety Outcome Measures [ Time Frame: Safety and tolerability assessments will be performed for a period of 7 days after administration of a single dose ]
Change History Complete list of historical versions of study NCT00546715 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2015)
  • 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 ]
    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.
  • 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 ]
    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.
  • 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 ]
    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.
  • 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 ]
    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.
  • 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 ]
    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.
  • 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 ]
    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.
  • 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 ]
    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.
  • Change From Baseline in Heart Rate to Day 7 or Discharge [ Time Frame: Baseline (Day 1), 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.
  • 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 ]
    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.
  • Change From Baseline in Blood Pressure to Day 7 or Discharge [ Time Frame: Baseline (Day 1), 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2007)
  • Pharmacokinetic Measures [ Time Frame: Pharmacokinetic assessments will be done for a period of 72 hours following administration of a single oral dose ]
  • Pharmacodynamic Measures [ Time Frame: Antiviral activity will be assessed by the magnitude and rate of change in plasma HCV RNA levels for a period of 7 days after dosing ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Single Ascending Dose Study of Daclatasvir (BMS-790052) in Hepatitis C Virus Infected Subjects
Official Title  ICMJE 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
Brief 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis C
Intervention  ICMJE
  • Drug: Daclatasvir
    Oral Solution, Oral, Single Dose
  • Drug: Placebo
    Oral Solution, Oral, Single Dose
Study Arms  ICMJE
  • Active Comparator: Dose Panel A

    Daclatasvir - 1 mg

    Placebo - 0 mg

    Interventions:
    • Drug: Daclatasvir
    • Drug: Placebo
  • Active Comparator: Dose Panel B

    Daclatasvir - 10 mg

    Placebo - 0 mg

    Interventions:
    • Drug: Daclatasvir
    • Drug: Placebo
  • Active Comparator: Dose Panel C

    Daclatasvir - 100 mg

    Placebo - 0 mg

    Interventions:
    • Drug: Daclatasvir
    • Drug: Placebo
  • Active Comparator: Dose Panel D

    Daclatasvir - 0.5 - 200 mg (to be determined)

    Placebo - 0 mg

    Interventions:
    • Drug: Daclatasvir
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 10, 2015)
95
Original Estimated Enrollment  ICMJE
 (submitted: October 17, 2007)
24
Actual Study Completion Date  ICMJE May 2008
Actual Primary Completion Date May 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • 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:

  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 49 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00546715
Other Study ID Numbers  ICMJE AI444-002
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP