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

NCT00546715 | Completed Phase 1 Results

• 1 other identifier: AI444-002
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 7

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

Conditions

Chronic Hepatitis C

Outcome Measures

Primary Outcomes (3)

• 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.

  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.

  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.

  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)

  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

  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)

  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)

  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)

  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

Study Arms (4)

Dose Panel A

ACTIVE COMPARATOR

Daclatasvir - 1 mg Placebo - 0 mg

Drug: Daclatasvir; Drug: Placebo

Dose Panel B

ACTIVE COMPARATOR

Daclatasvir - 10 mg Placebo - 0 mg

Drug: Daclatasvir; Drug: Placebo

Dose Panel C

ACTIVE COMPARATOR

Daclatasvir - 100 mg Placebo - 0 mg

Drug: Daclatasvir; Drug: Placebo

Dose Panel D

ACTIVE COMPARATOR

Daclatasvir - 0.5 - 200 mg (to be determined) Placebo - 0 mg

Drug: Daclatasvir; Drug: Placebo

Interventions

Daclatasvir DRUG

Oral Solution, Oral, Single Dose

Dose Panel A; Dose Panel B; Dose Panel C; Dose Panel D

Placebo DRUG

Oral Solution, Oral, Single Dose

Dose Panel A; Dose Panel B; Dose Panel C; Dose Panel D

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (7)

Advanced Clinical Research Institute

Anaheim, California, 92801, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Parexel International Corporation

Baltimore, Maryland, 21225, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Bristol-Myers Squibb Clinical Pharmacology Unit

Hamilton, New Jersey, 08690, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University Of Virginia Digestive Health Center Of Excellence

Charlottesville, Virginia, 22908, United States

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

daclatasvir

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2007
• First Posted: October 19, 2007
• Study Start: November 1, 2007
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: November 18, 2015
• Results First Posted: September 10, 2015

Record last verified: 2015-10

Locations

US (7)