Clinical trial NCT00663208: A Multiple Ascending Dose Study of Daclatasvir (BMS-790052) in Hepatitis C Virus Genotype 1 Infected Subjects
Official title: Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Antiviral Activity and Safety, Tolerability, and Pharmacokinetics of Daclatasvir in Subjects Infected With Hepatitis C Virus Genotype 1
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2008-04-22
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to assess the change in Hepatitis C Virus RNA during dosing with daclatasvir and during the follow-up period in subjects with chronic hepatitis C infection


Eligibility criteria: Inclusion Criteria:

* Chronically infected with Hepatitis C Virus (HCV) genotype 1
* Treatment naive or treatment non-responders or treatment intolerant; and not co-infected with HIV or Hepatitis B Virus
* HCV RNA viral load of ≥10\*5 IU/mL
* BMI 18 to 35kg/m²

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
* HIV and/or HBV positive
* Major surgery within 4 weeks of study drug administration and any gastrointestinal surgery that could impact the absorption of study drug

WOCBP will be enrolled as in-patient for 16 days

Primary outcomes:
measure: Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA of All Participants
timeFrame: Baseline, Day 7
Secondary outcomes:
measure: Change From Baseline at Day 7 in log10 Hepatitis C Virus (HCV) RNA Levels of Participants Without Baseline Drug Resistance
timeFrame: Baseline, Day 7
measure: Change From Baseline at 24 h Post Dose on Day 1 in log10 Hepatitis C Virus (HCV) RNA of Participants Without Baseline Drug Resistance
timeFrame: Baseline, 2, 4, 6, 8, 12, 16, 20, and 24 hours post dose on Day 1
measure: Change From Baseline to Day 4 in log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance
timeFrame: Baseline to Day 4
measure: Change From Baseline to Day 14 in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance
timeFrame: Baseline to Day 14
measure: Time to Maximum Decline From Baseline in Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance
timeFrame: Day 1 up to Day 14
measure: Maximum Decline From Baseline in Log10 Hepatitis C Virus (HCV) RNA in Participants Without Baseline Drug Resistance
timeFrame: Day 1 up to Day 14
measure: Maximum Observed Plasma Concentration (Cmax) and Minimum Observed Plasma Concentration (Cmin) of Daclatasvir on Days 1 and 14
timeFrame: 0 hour (pre-dose) 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hour (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13 and 24, 48 and 72 hours (post morning dose) at Day 14
measure: Area Under the Concentration-time Curve (AUC) in 1 Dosing Interval of Daclatasvir at Days 1 and 14
timeFrame: 0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hr (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14
measure: Plasma Half-life (T-half) of Daclatasvir at Day 14
timeFrame: 0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hr (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14
measure: Apparent Total Body Clearance (CLT/F) of Daclatasvir on Day 14
timeFrame: 0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hour (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14
measure: Average Observed Plasma Concentration (Css-av) at Steady State of Daclatasvir at Days 1 and 14
timeFrame: 0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hr (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11,13, and 24, 48 and 72 hours (post morning dose) at Day 14
measure: Accumulation Index (AI) AUC(TAU), AI Cmax, and Degree of Fluctuation (DF) of Daclatasvir on Day 14
timeFrame: 0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hour (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14
measure: Time of Maximum Observed Plasma Concentration (Tmax) of Daclatasvir on Days 1 and 14
timeFrame: 0 hour (pre-dose) 0.5, 1,1.5, 2, 3, 4, 6, 8 and 12 hours (post morning dose) at Day1 and Day 14, 0 hour (pre-dose) at Days 2, 3, 4, 5, 7, 9, 11, 13, and 24, 48 and 72 hours (post morning dose) at Day 14
measure: Correlation Coefficients Between Measures of Decline in log10 Hepatitis C Virus (HCV) RNA and Daclatasvir PK Parameters Cmax, AUC(TAU), and Cmin on Day 14 in Participants Without Baseline Drug Resistance
timeFrame: Day 4, Day 14
measure: Number of Participants With Serious Adverse Events (SAEs), Discontinuation Due to Adverse Events (AEs), and Who Died
timeFrame: Day 1 to Day 182 or Day of Discharge
measure: Number of Participants With Marked Laboratory Abnormalities in Hematology
timeFrame: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28
measure: Number of Participants With Marked Abnormalities in Liver and Kidney Function Laboratory Tests and Electrolytes
timeFrame: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28
measure: Number of Participants With Marked Laboratory Abnormalities in Lipase and Glucose
timeFrame: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28
measure: Number of Participants With Marked Laboratory Abnormalities in Urinalysis
timeFrame: Screening, Day 3, Day 7, Day 11, Day 14, and Day 28
measure: Number of Participants With Clinically Relevant Change From Baseline in Vital Signs
timeFrame: Screening, Day -1 and prior to morning dose on Day 1, 2, 14, and 28
measure: Number of Participants Meeting Pre-Specified Criteria in Electrocardiogram Parameters
timeFrame: Screening, Day 2, 3, 5, 7, 9, 11, 13, 15, 21 and 28
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Advanced Clinical Res Inst
state: California
city: Cypress
country: United States
facility: West Coast Clinical Trials, Llc
state: California
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Miami
country: United States
facility: Elite Research Institute
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Baltimore
country: United States
facility: Parexel International Corporation
state: Maryland
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: Santurce
country: Puerto Rico
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Nettles RE, Gao M, Bifano M, Chung E, Persson A, Marbury TC, Goldwater R, DeMicco MP, Rodriguez-Torres M, Vutikullird A, Fuentes E, Lawitz E, Lopez-Talavera JC, Grasela DM. Multiple ascending dose study of BMS-790052, a nonstructural protein 5A replication complex inhibitor, in patients infected with hepatitis C virus genotype 1. Hepatology. 2011 Dec;54(6):1956-65. doi: 10.1002/hep.24609.