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
Overview
- Phase
- Phase 2
- Intervention
- BMS-955176
- Conditions
- Infection, Human Immunodeficiency Virus
- Sponsor
- ViiV Healthcare
- Enrollment
- 107
- Locations
- 1
- Primary Endpoint
- Change in Plasma Log10 HIV-1 Ribonucleic Acid (RNA) Levels From Baseline to Day 11
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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
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
Investigators
Eligibility Criteria
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
Arms & Interventions
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
Intervention: BMS-955176
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
Intervention: Placebo matching with BMS-955176
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
Intervention: BMS-955176
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
Intervention: Atazanavir
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
Intervention: Placebo matching with BMS-955176
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
Intervention: BMS-955176
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
Intervention: Placebo matching with BMS-955176
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
Intervention: BMS-955176
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
Intervention: Placebo matching with BMS-955176
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
Intervention: BMS-955176
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
Intervention: Atazanavir
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
Intervention: BMS-955176
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
Intervention: Ritonavir
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
Intervention: Atazanavir
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
Intervention: Ritonavir
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
Intervention: Tenofovir
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
Intervention: Emtricitabine
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
Intervention: BMS-955176
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
Intervention: Placebo matching with BMS-955176
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
Intervention: BMS-955176
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
Intervention: Placebo matching with BMS-955176
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
Intervention: BMS-955176
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
Intervention: Placebo matching with BMS-955176
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
Intervention: BMS-955176
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
Intervention: Placebo matching with BMS-955176
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
Intervention: BMS-955176
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
Intervention: Atazanavir
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
Intervention: BMS-955176
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
Intervention: Placebo matching with BMS-955176
Outcomes
Primary Outcomes
Change in Plasma Log10 HIV-1 Ribonucleic Acid (RNA) Levels From Baseline to Day 11
Time Frame: Baseline (Day 1) and Day 11 after the final dose with BMS-955176
Antiviral activity of BMS-955176 was estimated by measuring the plasma HIV-1 RNA levels in the HIV-1 infected participants. Change in the plasma HIV-1 RNA levels were measured in the participants infected with HIV-1 clade B and C who received BMS-955176 monotherapy. Baseline was Day 1. Change from Baseline was post-Baseline individual values minus Baseline values.
Secondary Outcomes
- Time to Reach Maximum Plasma Concentration (Tmax) - Part A and C(Pre-dose Day 1 and Day 10)
- Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Related SAEs, Discontinuations Due to SAEs, Adverse Events (AEs), and Discontinuations Due to AEs During the Study(Day 1 to end of the study (Day 42))
- Maximum Decline From Baseline in Log10 HIV-1 RNA - Part A and C(Baseline (Day 1) up to Day 24)
- Maximum Decline From Baseline in Log10 HIV-1 RNA - Part B(Baseline (Day 1) up to Day 42)
- Time to Maximum Decline in Log 10 HIV-1 RNA - Part A and C(Baseline (Day 1) up to Day 24)
- Time to Maximum Decline in Log 10 HIV-1 RNA - Part B(Baseline (Day 1) up to Day 42)
- Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Counts - Part A and C(Baseline (Day 1) up to Day 24)
- Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Counts - Part B(Baseline (Day 1) up to Day 42)
- Percent Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Percent - Part A and C(Baseline (Day 1) up to Day 24)
- Percent Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Percent - Part B(Baseline (Day 1) up to Day 42)
- Time to Reach Maximum Plasma Concentration (Tmax) - Part B(Pre-dose Day 1 and Day 28)
- Maximum Observed Plasma Concentrations (Cmax) - Part A and C(Pre-dose Day 1 and Day 10)
- Plasma Concentration 24 Hours Post-Dose (C24) - Part A and C(24 hours post-dose)
- Maximum Observed Plasma Concentrations (Cmax) - Part B(Pre-dose Day 1 and Day 28)
- Plasma Concentration 24 Hours Post-Dose (C24) - Part B(24 hours post-dose)
- Area Under The Plasma Concentration - Time Curve Over the Dosing Interval (AUC([Tau]) - Part A and C(Pre-dose Day 1 and Day 10)
- Area Under The Plasma Concentration - Time Curve Over the Dosing Interval (AUC[Tau]) - Part B(Pre-dose Day 1 and Day 28)
- Accumulation Index (AI): Part A and C(Baseline and Day 10)
- Apparent Total Body Clearance: Part A and C(Baseline (Day 1) to Day 10)
- Degree of Fluctuation (DF): Part A and C(Baseline (Day 1) to Day 10)
- Average Observed Plasma Concentration at Steady State (Css-avg): Part A and C(Baseline (Day 1) to Day 10)
- Plasma Half-life: Part A and C(Baseline (Day 1) to Day 10)
- Number of Participants With Clinically Significant Grade 3/4 Laboratory Abnormalities From Baseline(Day 1 to up to end of the study (Day 42))
- Number of Participants With Clinically Significant Changes in Heart Rate(Day 1 to end of the study (Day 42))
- Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)(Day 1 to end of the study (Day 42))
- Number of Participants With Clinically Significant Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)(Day 1 to end of the study (Day 42))
- Number of Participants With Abnormal Changes in Physical Examination(Day 1 to end of the study (Day 42))