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

Sponsor:	Bristol-Myers Squibb
Information provided by:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01012895

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 II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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

Drug Information available for: Ribavirin Interferon alfa-2a Peginterferon Alfa-2a Interferon alfa-n1 Interferons

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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	120
Study Start Date:	December 2009
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	September 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

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01012895

Contacts

Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email:		Clinical.Trials@bms.com
Contact: First line of email MUST contain NCT# & Site#. Only trial sites that are recruiting have contact information at this time.

Locations

United States, California
Advanced Clinical Res Inst	Recruiting
Anaheim, California, United States, 92801
Contact: Michael P. Demicco, Site 004 714-774-7777
Southern California Liver Centers	Recruiting
Coronado, California, United States, 92118
Contact: Tarek Hassanein, Site 028 619-522-0330
San Jose Gastroenterology	Recruiting
San Jose, California, United States, 95128
Contact: Huy Ngoc Trinh, Site 018 408-213-3941
United States, Colorado
University Of Colorado Denver & Hospital	Recruiting
Aurora, Colorado, United States, 80045
Contact: Gregory Everson, Site 007 303-724-1877
United States, Maryland
Mercy Medical Center	Recruiting
Baltimore, Maryland, United States, 21202
Contact: Paul Thuluvath, Site 014 410-576-5389
United States, Massachusetts
Claudia T. Martorell, Md	Recruiting
Springfield, Massachusetts, United States, 01105
Contact: Claudia T. Martorell, Site 002
United States, North Carolina
Charlotte Gastroenterology & Hepatology, Pllc	Recruiting
Charlotte, North Carolina, United States, 28207
Contact: John S. Hanson, Site 016 704-375-9485
Carolinas Center For Liver Disease	Recruiting
Statesville, North Carolina, United States, 28677
Contact: Robert W. Reindollar, Site 013 704-978-1144
United States, Texas
Local Institution	Not yet recruiting
Arlington, Texas, United States, 76012
Contact: Site 012
Liver Associates Of Texas	Recruiting
Houston, Texas, United States, 77030
Contact: Victor Ankoma-Sey, Site 030
Alamo Medical Research	Recruiting
San Antonio, Texas, United States, 78215
Contact: Eric J Lawitz, Site 003 210-253-3426
United States, Virginia
Metropolitan Research	Recruiting
Fairfax, Virginia, United States, 22031
Contact: Vinod K. Rustgi, Site 010 703-698-9254
France
Local Institution	Recruiting
Clichy Cedex, France, 92118
Contact: Site 019
Local Institution	Recruiting
Creteil Cedex, France, 94010
Contact: Site 020
Local Institution	Recruiting
Marseille Cedex 08, France, 13285
Contact: Site 026
Local Institution	Recruiting
Montpellier Cedex 5, France, 34295
Contact: Site 021
Local Institution	Recruiting
Paris Cedex 12, France, 75571
Contact: Site 023
Local Institution	Recruiting
Paris Cedex 13, France, 75651
Contact: Site 025
Local Institution	Recruiting
Paris Cedex 14, France, 75679
Contact: Site 022
Local Institution	Recruiting
Pessac, France, 33604
Contact: Site 024
Puerto Rico
Local Institution	Recruiting
San Juan, Puerto Rico, 00927
Contact: Site 027

Sponsors and Collaborators

Bristol-Myers Squibb

Investigators

Study Director:

Bristol-Myers Squibb

More Information

Additional Information:

BMS Clinical Trials Disclosure 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

No publications provided by Bristol-Myers Squibb

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

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.

Responsible Party:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01012895 History of Changes
Other Study ID Numbers:	AI447-011, 2010-024637-23
Study First Received:	November 12, 2009
Last Updated:	February 2, 2012
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board; European Union: European Medicines Agency; France: Afssaps - French Health Products Safety Agency

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2a

Interferons
Ribavirin
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antimetabolites

ClinicalTrials.gov processed this record on February 09, 2012