Study to Evaluate a HIV Drug for the Treatment of HIV Infection - Full Text View

Purpose

The primary purpose of this study is to study the safety and tolerability of a HIV drug and to evaluate a decrease of HIV-1 virus level in blood after treatments in HIV-1 infected patients

Condition	Intervention	Phase
HIV-1 Infection	Drug: BMS-955176 Drug: Placebo matching with BMS-955176 Drug: Atazanavir Drug: Ritonavir Drug: Tenofovir Drug: Emtricitabine	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Pharmacodynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	Randomized, Placebo-Controlled, Multiple-Dose Study to Evaluate the Pharmacodynamics, Safety and Pharmacokinetics of BMS-955176 (Double-Blinded) and BMS-955176 With Atazanavir +/- Ritonavir (Open-Labeled) in HIV-1 Infected Subjects

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Emtricitabine Tenofovir Ritonavir Atazanavir Tenofovir Disoproxil Fumarate Atazanavir sulfate

U.S. FDA Resources

Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:

Change in plasma HIV-1 RNA levels from baseline (Day 1-predose) on Day 11 with monotherapy [ Time Frame: Baseline (Day 1-predose) and Day 11 after the final dose with BMS-955176 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Safety based on frequency of Adverse events (AEs), serious AEs, discontinuations due to AEs, findings of marked abnormalities in vital signs, clinical laboratory tests, ECG readings and physical examinations [ Time Frame: Up to day 24 (Groups 1-4, 8-10 and 13), up to day 28 (optional group 11) and up to day 42 (Part B) ] [ Designated as safety issue: Yes ]
Time course of the change from baseline in plasma log10 HIV-1 RNA levels and the time of maximum decrease during the 10-day monotherapy and combination therapy of BMS-955176 with Atazanavir (ATV) +/- Ritonavir (RTV) [ Time Frame: Day 1-24 (Groups 1-4, 8-10 & 13), Day 1-28 (optional group 11) and Day 1-42 (Part B) ] [ Designated as safety issue: No ]
Change from baseline in CD4+ and CD8+ lymphocyte counts and percentages following monotherapy and combination therapy of BMS-955176 with ATV +/- RTV in HIV-1 infected subjects [ Time Frame: Day 1-24 (Groups 1-4, 8-10 & 13), Day 1-28 (optional group 11) and Day 1-42 (Part B) ] [ Designated as safety issue: No ]
Maximum observed plasma concentration (Cmax) of BMS-955176 [ Time Frame: 26 timepoints up to Day 10 (Groups 1-4, 8-10 & 13), 30 timepoints up to Day 14 (optional group 11) and 24 timepoints up to Day 28 (Part B) ] [ Designated as safety issue: No ]
Observed concentration at 24 hours postdose (C24) of BMS-955176 [ Time Frame: 26 timepoints up to Day 10 (Groups 1-4, 8-10 & 13), 30 timepoints up to Day 14 (optional group 11) and 24 timepoints up to Day 28 (Part B) ] [ Designated as safety issue: No ]
Time of maximum observed plasma concentration (Tmax) of BMS-955176 [ Time Frame: 26 timepoints up to Day 10 (Groups 1-4, 8-10 & 13), 30 timepoints up to Day 14 (optional group 11) and 24 timepoints up to Day 28 (Part B) ] [ Designated as safety issue: No ]
Trough observed plasma concentration (Ctrough) of BMS-955176 [ Time Frame: 26 timepoints up to Day 10 (Groups 1-4, 8-10 & 13), 30 timepoints up to Day 14 (optional group 11) and 24 timepoints up to Day 28 (Part B) ] [ Designated as safety issue: No ]
Area under the concentration-time curve in one dosing interval [AUC(TAU)] of BMS-955176 [ Time Frame: 26 timepoints up to Day 10 (Groups 1-4, 8-10 & 13), 30 timepoints up to Day 14 (optional group 11) and 24 timepoints up to Day 28 (Part B) ] [ Designated as safety issue: No ]
Accumulation Index (AI), calculated as ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose of BMS-955176 [ Time Frame: 26 timepoints up to Day 10 (Groups 1-4, 8-10 & 13), 30 timepoints up to Day 14 (optional group 11) and 24 timepoints up to Day 28 (Part B) ] [ Designated as safety issue: No ]
Apparent total body clearance (CLT/F) of BMS-955176 [ Time Frame: 26 timepoints up to Day 10 (Groups 1-4, 8-10 & 13), 30 timepoints up to Day 14 (optional group 11) and 24 timepoints up to Day 28 (Part B) ] [ Designated as safety issue: No ]
Terminal Plasma half-life (T-Half)-after last dose only of BMS-955176 [ Time Frame: Day 10 (Part A and C), Day 14 (optional group 11) and Day 28 (Part B) ] [ Designated as safety issue: No ]
Degree of Fluctuation (DF), calculated as steady state (Cmax-C24) / (AUC(TAU) / 24) of BMS-955176 [ Time Frame: 26 timepoints up to Day 10 (Groups 1-4, 8-10 & 13), 30 timepoints up to Day 14 (optional group 11) and 24 timepoints up to Day 28 (Part B) ] [ Designated as safety issue: No ]
Average steady-state plasma concentration (Css-av), calculated as AUC(TAU) / TAU of BMS-955176 [ Time Frame: 26 timepoints up to Day 10 (Groups 1-4, 8-10 & 13), 30 timepoints up to Day 14 (optional group 11) and 24 timepoints up to Day 28 (Part B) ] [ Designated as safety issue: No ]


Enrollment:	107
Study Start Date:	March 2013
Study Completion Date:	November 2014
Primary Completion Date:	November 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Part A-Group 1: BMS-955176 (5 mg) or Placebo BMS-955176 5 mg solution by mouth once daily for 10 days OR Placebo matching with BMS-955176 0 mg solution by mouth once daily for 10 days	Drug: BMS-955176 Drug: Placebo matching with BMS-955176
Experimental: Part A-Group 2: BMS-955176 (10 mg) or Placebo BMS-955176 10 mg solution by mouth once daily for 10 days OR Placebo matching with BMS-955176 0 mg solution by mouth once daily for 10 days	Drug: BMS-955176 Drug: Placebo matching with BMS-955176
Experimental: Part A-Group 3: BMS-955176 (20 mg) or Placebo BMS-955176 20 mg solution by mouth once daily for 10 days OR Placebo matching with BMS-955176 0 mg solution by mouth once daily for 10 days	Drug: BMS-955176 Drug: Placebo matching with BMS-955176
Experimental: Part A-Group 4: BMS-955176 (40 mg) or Placebo BMS-955176 40 mg solution by mouth once daily for 10 days OR Placebo matching with BMS-955176 0 mg solution by mouth once daily for 10 days	Drug: BMS-955176 Drug: Placebo matching with BMS-955176
Experimental: Part B-Group 5: BMS-955176 + Atazanavir BMS-955176 40 mg solution by mouth once daily for 28 days Atazanavir 2 x 200 mg capsules by mouth once daily for 28 days	Drug: BMS-955176 Drug: Atazanavir
Experimental: Part B-Group 6: BMS-955176 + Atazanavir + Ritonavir BMS-955176 40 mg solution by mouth once daily for 28 days Atazanavir 1 x 300 mg capsules by mouth once daily for 28 days Ritonavir 1 x 100 mg tablet by mouth once daily for 28 days	Drug: BMS-955176 Drug: Atazanavir Drug: Ritonavir
Experimental: Part B-Group 7: Atazanavir+Ritonavir+Tenofovir+Emtricitabine Atazanavir 1 x 300 mg capsule by mouth once daily for 28 days Ritonavir 1 x 100 mg tablet by mouth once daily for 28 days Tenofovir 1 x 300 mg tablet by mouth once daily for 28 days Emtricitabine 1 x 200 mg capsule once daily for 28 days	Drug: Atazanavir Drug: Ritonavir Drug: Tenofovir Drug: Emtricitabine
Experimental: Part C-Group 8: BMS-955176 (40 mg) or Placebo BMS-955176 40 mg solution by mouth once daily for 10 days OR Placebo matching with BMS-955176 0 mg solution by mouth once daily for 10 days	Drug: BMS-955176 Drug: Placebo matching with BMS-955176
Experimental: Part A-Group 9: BMS-955176 (80 mg) or Placebo BMS-955176 80 mg solution by mouth once daily for 10 days OR Placebo matching with BMS-955176 0 mg solution by mouth once daily for 10 days	Drug: BMS-955176 Drug: Placebo matching with BMS-955176
Experimental: Part A-Group 10: BMS-955176 (120 mg) or Placebo BMS-955176 120 mg solution by mouth once daily for 10 days OR Placebo matching with BMS-955176 0 mg solution by mouth once daily for 10 days	Drug: BMS-955176 Drug: Placebo matching with BMS-955176
Experimental: Part A-Group 11 (Optional): BMS-955176 (≤120 mg) or Placebo BMS-955176 ≤120 mg solution by mouth once daily for 14 days OR Placebo matching with BMS-955176 0 mg solution by mouth once daily for 14 days	Drug: BMS-955176 Drug: Placebo matching with BMS-955176
Experimental: Part B-Group 12: BMS-955176 (80 mg) + Atazanavir BMS-955176 80 mg solution by mouth once daily for 28 days Atazanavir 2 x 200 mg capsules by mouth once daily for 28 days	Drug: BMS-955176 Drug: Atazanavir
Experimental: Part C-Group 13: BMS-955176 (120 mg) or Placebo BMS-955176 120 mg solution by mouth once daily for 10 days OR Placebo matching with BMS-955176 0 mg solution by mouth once daily for 10 days	Drug: BMS-955176 Drug: Placebo matching with BMS-955176

Detailed Description:

Masking: Open-Part B. Double Blind-Parts A and C

Gender: Both female and male participants for Parts A and C. Male participants for Part B.

HIV = Human Immunodeficiency Virus RNA = Ribonucleic acid

Eligibility


Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

Age 18-55 years inclusive
Men and women: (Parts A and C); men only (Part B)
Women of childbearing potential (WOCBP) must not be pregnant and nursing
BMI: 18.0-35.0 kg/m2
Subjects are infected with HIV-1 (clades B or C) and meet following criteria at the screening:

i) Plasma HIV-1 RNA ≥5,000 copies/mL; ii) Antiretroviral treatment naive (defined as <1 week of ARV treatment) or ART-experienced (protease inhibitor and/or maturation inhibitor naive); iii) Subjects are not eligible for HIV-1 treatment based on the United States Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents or have declined initiation of cART iv) CD4+ lymphocyte measurement ≥200 cells/μL; v) In Parts A and B, all subjects are infected with HIV-1 clade B vi) In Part C, all subjects are infected with HIV-1 clade C

Exclusion Criteria:

History of genotypic and/or phenotypic drug resistance testing showing resistance to protease inhibitors
Any significant acute or chronic medical illness which is not stable or is not controlled with medication or not consistent with HIV-1 infection
Receive antiretroviral treatment within 12 weeks prior to screening
Currently co-infected with hepatitis C or hepatitis B
Previously received an HIV maturation inhibitor or HIV protease inhibitor
Current or recent (within 3 months of study drug administration) gastrointestinal disease
Any major surgery within 4 weeks of study drug administration
Acute diarrhea lasting ≥1 day, within 3 weeks prior to randomization
Subjects with history of Gilbert's syndrome
Subjects previously received an HIV maturation inhibitor or HIV protease inhibitor
A personal history of clinically relevant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de pointes. A personal or family history of long QT syndrome
Patients who are unwilling to practice adequate infection protection during and after study participation to minimize potential for spread of HIV infection, including HIV which may have developed resistance to HIV maturation inhibitor and/or ATV
Any gastrointestinal surgery that could impact upon the absorption of study drug
Smoking >10 cigarettes per day
PR ≥210 msec; QRS ≥120 msec; QT ≥500 msec; and QTcF ≥470 msec for women and ≥450 msec for men
Evidence of second or third degree heart block prior to study drug
Absolute Neutrophil Count <(ANC) 0.7 x lower limit of normal (LLN)
Hemoglobin <0.8 x LLN
Alanine aminotransferase (ALT) >1.25 x upper limit of normal (ULN)
Aspartate aminotransferase (AST) >1.25 x ULN
Total Bilirubin >1.25 x ULN
Creatinine clearance <60 mL/mim
Positive urine screen for drugs of abuse without a valid prescription (subjects positive for cannabinoids and/or amphetamines will be included)
Positive blood screen for hepatitis C virus (HCV) RNA, hepatitis B surface antigen (consistent with active or chronic hepatitis B), or HIV-2 antibody
History of any significant drug allergy

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01803074

Locations


Germany
Local Institution
Berlin, Germany, 10117
South Africa
Local Institution
Pretoria, Gauteng, South Africa, 0087

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

FDA Safety Alerts and Recalls This link exits the ClinicalTrials.gov site

No publications provided


Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01803074 History of Changes
Other Study ID Numbers:	AI468-002, 2012-004124-38
Study First Received:	March 1, 2013
Last Updated:	February 6, 2015
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:


Infection Atazanavir Emtricitabine Ritonavir Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents	Antiviral Agents Enzyme Inhibitors HIV Protease Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Protease Inhibitors Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015