Multiple Ascending Dose Study of BMS-929075 in Hepatitis C Virus (HCV) Infected Patients

Chronic Hepatitis C Clinical Trial

Official title:

Double-Blinded, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Antiviral Activity, Safety, Tolerability, and Pharmacokinetics of BMS-929075 in Treatment Naive Subjects Infected With Hepatitis C Virus Genotype 1

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01525212
• Other study ID #: AI457-002
• Status: Withdrawn
• Phase: Phase 1
• First received: January 31, 2012
• Last updated: June 19, 2013
• Start date: April 2012
• Est. completion date: February 2013

Study information

• Verified date: June 2013
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationNew Zealand: Medsafe
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the change from baseline in HCV Ribonucleic acid (RNA) on Day 4 following three days of dosing with BMS-929075 in chronically genotype subtype 1a and 1b HCV infected subjects

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Men and women, ages 18 to 65 years, inclusive

• Subjects who are naive to HCV treatment, defined as no previous exposure to an Interferon (IFN), Ribavirin (RBV); or any HCV-specific direct acting antiviral or experimental therapy

• HCV genotype 1a or 1b only

• HCV RNA viral load of = 100,000 IU/mL

• Have one of the following: i) Documented Fibrotest score of = 0.72 and AST to platelet ratio index (APRI) = 2; or ii) Documented liver biopsy within 12 months preceding Day 1 showing absence of cirrhosis

• Body Mass Index (BMI) of 18.0 to 35.0 kg/m2, inclusive

Exclusion Criteria:

• Any significant acute or chronic medical illness

• History of adrenal gland disease, including but not limited to adrenal insufficiency or Cushing's syndrome

• 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 that could impact upon the absorption of study drug

• Positive for hepatitis B surface antigen (HBsAg)

• Positive for Human Immunodeficiency Virus (HIV) -1 and/or -2 antibodies

• Smoking > 10 cigarettes per day

• Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 5x upper limit of normal (ULN)

• Total Bilirubin = 1.5x ULN

• Hemoglobin < 10 g/dL

• Platelets < 75,000 cell/µL

• ALC (absolute lymphocyte count) < 1000 cell/µL

• Creatinine clearance (as estimated by method of Cockcroft and Gault) less than 60 mL/min

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• BMS-929075
Oral Suspension, = 25 mg, Once daily, 3 days
• BMS-929075
Oral Suspension, = 100 mg, Once daily, 3 days
• BMS-929075
Oral Suspension, = 400 mg, Once daily, 3 days
• BMS-929075
Oral Suspension, (= 800 mg, Once daily) OR (= 400 mg, Twice daily), 3 days
• Placebo matching BMS-929075
Oral Suspension, 0 mg, Once daily, 3 days
• Placebo matching BMS-929075
Oral Suspension, 0 mg, (Once daily for = 800 mg group) OR (Twice daily for = 400 mg group), 3 days

Locations

Country	Name	City	State
Australia	Local Institution	Adelaide	South Australia
Australia	Local Institution	Herston	Queensland
Australia	Local Institution	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HCV RNA level on Day 4		Within 4 days after the first dose	No
Secondary	Maximum decrease from baseline in plasma HCV RNA levels during the period from Day 1 to Day 28		Days 1-28	No
Secondary	Time course of the change from baseline in plasma HCV RNA levels and the time of maximum decrease during the period of Day 1 through Day 28		Days 1-28	No
Secondary	Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, ECGs, physical examinations, and clinical laboratory tests		Days 1-28 (with SAE from screening to Day 30)	Yes
Secondary	Maximum observed plasma concentration (Cmax) of BMS-929075 derived from plasma concentration versus time		Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h)	No
Secondary	Minimum observed plasma concentration (Cmin) of BMS-929075 derived from plasma concentration versus time		Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h)	No
Secondary	Trough observed plasma concentration (Ctrough) of BMS-929075 derived from plasma concentration versus time		Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h)	No
Secondary	Time of maximum observed plasma concentration (Tmax) of BMS-929075 derived from plasma concentration versus time		Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h)	No
Secondary	Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-929075 derived from plasma concentration versus time		Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h)	No
Secondary	Plasma half-life (T-HALF) of BMS-929075 derived from plasma concentration versus time		Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h)	No
Secondary	Protein Binding (PB) of BMS-929075 derived from plasma concentration versus time		Day 3 (0h and 2h)	No
Secondary	Fraction of free drug in plasma (fu) of BMS-929075 derived from plasma concentration versus time		Day 1 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h), Day 2, and Day 3 (0h, 0.5h, 1 h, 1.5h, 2h, 3h, 4h, 6h, 8h, 12h,24h, 36h, 48h and 72h)	No
Secondary	The relationship between antiviral activity and measures of exposure to BMS-929075		Days 1-6	No

External Links

•   BMS clinical trial educational resource
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