Clinical trial NCT01012895: Study to Determine the Effectiveness of Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) Infected Patients Who Have Previously Failed Standard of Care
Official title: Parallel, Open-Label, Randomized, Multiple-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-790052 and BMS-650032 in Combination in Null Responders to Standard of Care Infected With Chronic 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: 2009-11-13
Enrollment: 215
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether BMS-650032 and BMS-790052 in combination alone, together with Ribavirin, or together with Interferon and Ribavirin are effective in the treatment of Hepatitis C in patients who have not responded to prior therapy.


Eligibility criteria: Inclusion Criteria:

* Male and female subjects ages 18 to 70 years
* HCV-Infected Genotype 1 Null responders to current standard of care
* Expansion Cohorts A1 and A2 are restricted to patients infected with HCV Genotype 1b only.

Exclusion Criteria:

* Evidence of a medical condition associate with chronic liver disease other than HCV
* History of variceal bleeding, hepatic encephalopathy, or ascites requiring management with diuretics or paracentesis
* History of Cancer within 5 years of enrollment
* History of gastrointestinal disease or surgical procedure (except Cholecystectomy)
* History of clinically significant cardiac disease
* History of Glucose-6-phosphate dehydrogenase (G6PD) deficiency
* Documented cirrhosis within 12 months prior to dosing
* Positive for Human Immunodeficiency Virus (HIV) or Hepatitis B Virus (HBV)
* Pregnant

Primary outcomes:
measure: Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in subjects' blood before, during and after treatment
timeFrame: 12 weeks post treatment
Secondary outcomes:
measure: Safety assessments will be based on medical review of the frequency of SAEs and AEs, discontinuations due to AEs, and abnormalities observed from vital sign and ECG measurements, physical examinations and clinical laboratory results
timeFrame: 12 weeks post-treatment
measure: Pharmacokinetic parameter maximum observed concentration [Cmax] will be derived from plasma concentration versus time. Trough concentration (Ctrough) and sparse Pharmacokinetics (PK) samples will also be collected.
timeFrame: Day 1 and Day 14
measure: Pharmacokinetic parameter trough observed concentration [Cmin] will be derived from plasma concentration versus time. Trough concentration (Ctrough) and sparse Pharmacokinetics (PK) samples will also be collected.
timeFrame: Days 1, Days 7, Days 14, Weeks 4, Weeks 8, Weeks 12, Weeks 16
measure: Pharmacokinetic parameter time of maximum observed concentration [Tmax] will be derived from plasma concentration versus time. Trough concentration (Ctrough) and sparse Pharmacokinetics (PK) samples will also be collected.
timeFrame: Day 1 and Day 14
measure: Pharmacokinetic parameter area under the concentration-time curve in one dosing interval [AUC(TAU)] will be derived from plasma concentration versus time. Trough concentration (Ctrough) and sparse Pharmacokinetics (PK) samples will also be collected.
timeFrame: Day 1 and Day 14
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Advanced Clinical Research Institute
state: California
city: Coronado
country: United States
facility: Southern California Liver Centers
state: California
city: San Jose
country: United States
facility: San Jose Gastroenterology
state: California
city: Aurora
country: United States
facility: University Of Colorado Denver & Hospital
state: Colorado
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Ann Arbor
country: United States
facility: University Of Michigan Health System
state: Michigan
city: Statesville
country: United States
facility: Carolinas Center For Liver Disease
state: North Carolina
city: Arlington
country: United States
facility: Texas Clinical Research Institute, Llc
state: Texas
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: Fairfax
country: United States
facility: Metropolitan Research
state: Virginia
city: Clichy Cedex
country: France
facility: Local Institution
city: Creteil Cedex
country: France
facility: Local Institution
city: Marseille Cedex 08
country: France
facility: Local Institution
city: Paris Cedex 12
country: France
facility: Local Institution
city: Paris Cedex 13
country: France
facility: Local Institution
city: Paris Cedex 14
country: France
facility: Local Institution
city: Pessac
country: France
facility: Local Institution
city: San Juan
country: Puerto Rico
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Kao JH, Jensen DM, Manns MP, Jacobson I, Kumada H, Toyota J, Heo J, Yoffe B, Sievert W, Bessone F, Peng CY, Roberts SK, Lee YJ, Bhore R, Mendez P, Hughes E, Noviello S. Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: a pooled analysis. Liver Int. 2016 Jul;36(7):954-62. doi: 10.1111/liv.13049. Epub 2016 Jan 24.
citation: McPhee F, Hernandez D, Yu F, Ueland J, Monikowski A, Carifa A, Falk P, Wang C, Fridell R, Eley T, Zhou N, Gardiner D. Resistance analysis of hepatitis C virus genotype 1 prior treatment null responders receiving daclatasvir and asunaprevir. Hepatology. 2013 Sep;58(3):902-11. doi: 10.1002/hep.26388. Epub 2013 Jul 16.
citation: Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R, Reindollar R, Rustgi V, McPhee F, Wind-Rotolo M, Persson A, Zhu K, Dimitrova DI, Eley T, Guo T, Grasela DM, Pasquinelli C. Preliminary study of two antiviral agents for hepatitis C genotype 1. N Engl J Med. 2012 Jan 19;366(3):216-24. doi: 10.1056/NEJMoa1104430.