Study to Determine the Effectiveness of Antiviral Combination Therapy to Treat Hepatitis C Virus (HCV) Infected Patients Who Have Previously Failed Standard of Care - Full Text View

Purpose

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.

Condition	Intervention	Phase
Chronic Hepatitis C	Drug: BMS-790052 Drug: BMS-650032 Drug: Pegylated-interferon alfa-2a Drug: Ribavirin	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Hepatitis C virus (HCV) ribonucleic acid (RNA) levels in subjects' blood before, during and after treatment [ Time Frame: 12 weeks post treatment ]

Secondary Outcome Measures:

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 [ Time Frame: 12 weeks post-treatment ]
Serious Adverse Events (SAEs), Adverse Events (AEs), Electrocardiogram (ECG)
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. [ Time Frame: Day 1 and Day 14 ]
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. [ Time Frame: Days 1, Days 7, Days 14, Weeks 4, Weeks 8, Weeks 12, Weeks 16 ]
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. [ Time Frame: Day 1 and Day 14 ]
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. [ Time Frame: Day 1 and Day 14 ]


Enrollment:	215
Study Start Date:	December 2009
Study Completion Date:	February 2014
Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1: Sentinel A BMS-790052 (60mg) once daily + BMS-650032 (600 mg) twice daily	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 600 mg, twice daily, 24 weeks
Experimental: Arm 2: Sentinel B BMS-790052 (60mg) once daily + BMS-650032 (600mg) twice daily + Pegylated-interferon alfa-2a + Ribavirin	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 600 mg, twice daily, 24 weeks Drug: Pegylated-interferon alfa-2a Syringe, Subcutaneous Injection, 180 µg, once weekly Other Name: Pegasys Drug: Ribavirin Tablets, Oral For subjects weighing < 75 kg: 1000 mg; For subjects weighing ≥ 75 kg: 1200 mg Twice daily (< 75 kg: 400 mg in ante meridian (AM) and 600 mg in post meridian (PM); ≥ 75 kg: 600 mg in AM and PM), 24 weeks Other Name: Copegus
Experimental: Arm 3: Expansion A1 BMS-790052 (60mg) once daily + BMS-650032 (200mg) twice daily	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 200mg, twice daily, 24 weeks
Experimental: Arm 4: Expansion A2 BMS-790052 (60mg) once daily + BMS-650032 (200mg) once daily	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 200 mg, once daily, 24 weeks
Experimental: Arm 5: Expansion B1 BMS-790052 (60mg) once daily + BMS-650032 (200 mg) twice daily + Pegylated-interferon alfa-2a + Ribavirin	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 200mg, twice daily, 24 weeks Drug: Pegylated-interferon alfa-2a Syringe, Subcutaneous Injection, 180 µg, once weekly Other Name: Pegasys Drug: Ribavirin Tablets, Oral For subjects weighing < 75 kg: 1000 mg; For subjects weighing ≥ 75 kg: 1200 mg Twice daily (< 75 kg: 400 mg in ante meridian (AM) and 600 mg in post meridian (PM); ≥ 75 kg: 600 mg in AM and PM), 24 weeks Other Name: Copegus
Experimental: Arm 6: Expansion B2 BMS-790052 (60mg) once daily + BMS-650032 (200 mg) once daily + Pegylated-interferon alfa-2a + Ribavirin	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 200 mg, once daily, 24 weeks Drug: Pegylated-interferon alfa-2a Syringe, Subcutaneous Injection, 180 µg, once weekly Other Name: Pegasys Drug: Ribavirin Tablets, Oral For subjects weighing < 75 kg: 1000 mg; For subjects weighing ≥ 75 kg: 1200 mg Twice daily (< 75 kg: 400 mg in ante meridian (AM) and 600 mg in post meridian (PM); ≥ 75 kg: 600 mg in AM and PM), 24 weeks Other Name: Copegus
Experimental: Arm 7: Expansion B3 BMS-790052 (60 mg) once daily + BMS-650032 (200 mg) twice daily + Ribavirin	Drug: BMS-790052 Tablets, Oral, 60 mg, once daily, 24 weeks Drug: BMS-650032 Tablets, Oral, 200mg, twice daily, 24 weeks Drug: Ribavirin Tablets, Oral For subjects weighing < 75 kg: 1000 mg; For subjects weighing ≥ 75 kg: 1200 mg Twice daily (< 75 kg: 400 mg in ante meridian (AM) and 600 mg in post meridian (PM); ≥ 75 kg: 600 mg in AM and PM), 24 weeks Other Name: Copegus

Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01012895

Locations


United States, California
Advanced Clinical Research Institute
Anaheim, California, United States, 92801
Southern California Liver Centers
Coronado, California, United States, 92118
San Jose Gastroenterology
San Jose, California, United States, 95128
United States, Colorado
University Of Colorado Denver & Hospital
Aurora, Colorado, United States, 80045
United States, Maryland
Mercy Medical Center
Baltimore, Maryland, United States, 21202
United States, Michigan
University Of Michigan Health System
Ann Arbor, Michigan, United States, 48109
United States, North Carolina
Carolinas Center For Liver Disease
Statesville, North Carolina, United States, 28677
United States, Texas
Texas Clinical Research Institute, Llc
Arlington, Texas, United States, 76012
Alamo Medical Research
San Antonio, Texas, United States, 78215
United States, Virginia
Metropolitan Research
Fairfax, Virginia, United States, 22031
France
Local Institution
Clichy Cedex, France, 92118
Local Institution
Creteil Cedex, France, 94010
Local Institution
Marseille Cedex 08, France, 13285
Local Institution
Paris Cedex 12, France, 75571
Local Institution
Paris Cedex 13, France, 75651
Local Institution
Paris Cedex 14, France, 75679
Local Institution
Pessac, France, 33604
Puerto Rico
Local Institution
San Juan, Puerto Rico, 00927

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators


Study Director:	Bristol-Myers Squibb	Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trial Information This link exits the ClinicalTrials.gov site

BMS clinical trial educational resource This link exits the ClinicalTrials.gov site

Investigator Inquiry form This link exits the ClinicalTrials.gov site

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.


Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01012895 History of Changes
Other Study ID Numbers:	AI447-011 2010-024637-23 ( EudraCT Number )
First Submitted:	November 12, 2009
First Posted:	November 13, 2009
Last Update Posted:	October 9, 2015
Last Verified:	September 2015

Additional relevant MeSH terms:


Hepatitis Hepatitis A Hepatitis C Hepatitis, Chronic Hepatitis C, Chronic Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Enterovirus Infections Picornaviridae Infections RNA Virus Infections	Flaviviridae Infections Interferons Ribavirin Interferon-alpha Peginterferon alfa-2a Antineoplastic Agents Antiviral Agents Anti-Infective Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Immunologic Factors Physiological Effects of Drugs