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Study to Evaluate a HIV Drug for the Treatment of HIV Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01803074
Recruitment Status : Completed
First Posted : March 4, 2013
Results First Posted : November 25, 2019
Last Update Posted : November 25, 2019
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

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

Condition or disease Intervention/treatment Phase
Infection, Human Immunodeficiency Virus HIV Infections Drug: BMS-955176 Drug: Placebo matching with BMS-955176 Drug: Atazanavir Drug: Ritonavir Drug: Tenofovir Drug: Emtricitabine Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 107 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, 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
Actual Study Start Date : April 4, 2013
Actual Primary Completion Date : November 29, 2014
Actual Study Completion Date : November 29, 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
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
BMS-955176

Drug: Placebo matching with BMS-955176
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
BMS-955176

Drug: Placebo matching with BMS-955176
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
BMS-955176

Drug: Placebo matching with BMS-955176
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
BMS-955176

Drug: Placebo matching with BMS-955176
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
BMS-955176

Drug: Atazanavir
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
BMS-955176

Drug: Atazanavir
Atazanavir

Drug: Ritonavir
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
Atazanavir

Drug: Ritonavir
Ritonavir

Drug: Tenofovir
Tenofovir

Drug: Emtricitabine
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
BMS-955176

Drug: Placebo matching with BMS-955176
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
BMS-955176

Drug: Placebo matching with BMS-955176
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
BMS-955176

Drug: Placebo matching with BMS-955176
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
BMS-955176

Drug: Placebo matching with BMS-955176
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
BMS-955176

Drug: Atazanavir
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
BMS-955176

Drug: Placebo matching with BMS-955176
Placebo matching with BMS-955176




Primary Outcome Measures :
  1. 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 Outcome Measures :
  1. Time to Reach Maximum Plasma Concentration (Tmax) - Part A and C [ Time Frame: Pre-dose Day 1 and Day 10 ]
    Time to reach the maximum plasma concentration was directly determined from concentration time data.

  2. 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 [ Time Frame: Day 1 to end of the study (Day 42) ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or unknown relationship to study drug.

  3. Maximum Decline From Baseline in Log10 HIV-1 RNA - Part A and C [ Time Frame: Baseline (Day 1) up to Day 24 ]
    Antiviral activity of BMS-955176 was estimated by measuring the plasma HIV-1 RNA levels in the HIV-1 infected participants. Maximum decline from Baseline in the plasma HIV-1 RNA levels were measured in the participants infected with HIV-1 clade B and C. Baseline was Day 1. Change from Baseline was post-Baseline individual values minus Baseline values.

  4. Maximum Decline From Baseline in Log10 HIV-1 RNA - Part B [ Time Frame: Baseline (Day 1) up to Day 42 ]
    Antiviral activity of BMS-955176 was estimated by measuring the plasma HIV-1 RNA levels in the HIV-1 infected participants. Maximum decline from Baseline in the plasma HIV-1 RNA levels were measured in the participants infected with HIV-1 clade B and C. Baseline was Day 1. Change from Baseline was post-Baseline individual values minus Baseline values.

  5. Time to Maximum Decline in Log 10 HIV-1 RNA - Part A and C [ Time Frame: Baseline (Day 1) up to Day 24 ]
    Antiviral activity of BMS-955176 was estimated by measuring the plasma HIV-1 RNA levels in the HIV-1 infected participants. Time to maximum decline in the plasma HIV-1 RNA levels were measured in the participants infected with HIV-1 clade B and C. Baseline was Day 1. Change from Baseline was post-Baseline individual values minus Baseline values.

  6. Time to Maximum Decline in Log 10 HIV-1 RNA - Part B [ Time Frame: Baseline (Day 1) up to Day 42 ]
    Antiviral activity of BMS-955176 was estimated by measuring the plasma HIV-1 RNA levels in the HIV-1 infected participants. Time to maximum decline in the plasma HIV-1 RNA levels were measured in the participants infected with HIV-1 clade B and C. Baseline was Day 1. Change from Baseline was post-Baseline individual values minus Baseline values.

  7. Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Counts - Part A and C [ Time Frame: Baseline (Day 1) up to Day 24 ]
    Change in the CD4+ and CD8+ cell counts from Baseline were measured in the participants infected with HIV-1 clade B and C who received BMS-955176 + ATV or BMS-955176 + ATV + RTV therapy. Baseline was Day 1. Change from Baseline was post-Baseline individual values minus Baseline values.

  8. Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Counts - Part B [ Time Frame: Baseline (Day 1) up to Day 42 ]
    Change in the CD4+ and CD8+ cell counts from Baseline were measured in the participants infected with HIV-1 clade B and C who received BMS-955176 + ATV or BMS-955176 + ATV + RTV therapy. Baseline was Day 1. Change from Baseline was post-Baseline individual values minus Baseline values.

  9. Percent Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Percent - Part A and C [ Time Frame: Baseline (Day 1) up to Day 24 ]
    Percent Change in the CD4+ and CD8+ cell counts from Baseline were measured in the participants infected with HIV-1 clade B and C who received BMS-955176 + ATV or BMS-955176 + ATV + RTV therapy. Baseline was Day 1. Change from Baseline was post-Baseline individual values minus Baseline values.

  10. Percent Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Percent - Part B [ Time Frame: Baseline (Day 1) up to Day 42 ]
    Percent Change in the CD4+ and CD8+ cell counts from Baseline were measured in the participants infected with HIV-1 clade B and C who received BMS-955176 + ATV or BMS-955176 + ATV + RTV therapy. Baseline was Day 1. Change from Baseline was post-Baseline individual values minus Baseline values.

  11. Time to Reach Maximum Plasma Concentration (Tmax) - Part B [ Time Frame: Pre-dose Day 1 and Day 28 ]
    Tmax was directly determined from concentration time data.

  12. Maximum Observed Plasma Concentrations (Cmax) - Part A and C [ Time Frame: Pre-dose Day 1 and Day 10 ]
    Cmax was defined as the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  13. Plasma Concentration 24 Hours Post-Dose (C24) - Part A and C [ Time Frame: 24 hours post-dose ]
    C24 was defined as the plasma concentration of BMS-955176 at 24 hours post-dose.

  14. Maximum Observed Plasma Concentrations (Cmax) - Part B [ Time Frame: Pre-dose Day 1 and Day 28 ]
    Cmax was defined as the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  15. Plasma Concentration 24 Hours Post-Dose (C24) - Part B [ Time Frame: 24 hours post-dose ]
    C24 was defined as the plasma concentration of BMS-955176 at 24 hours post-dose.

  16. Area Under The Plasma Concentration - Time Curve Over the Dosing Interval (AUC([Tau]) - Part A and C [ Time Frame: Pre-dose Day 1 and Day 10 ]
    AUC(tau) was defined as the area under the plasma concentration - time curve over the dosing interval.

  17. Area Under The Plasma Concentration - Time Curve Over the Dosing Interval (AUC[Tau]) - Part B [ Time Frame: Pre-dose Day 1 and Day 28 ]
    AUC(tau) was defined as the area under the plasma concentration - time curve over the dosing interval.

  18. Accumulation Index (AI): Part A and C [ Time Frame: Baseline and Day 10 ]
    Accumulation index was calculated by dividing the AUC(tau) or Cmax or C24 of BMS-955176 on Day 10 by the AUC(TAU) or Cmax or C24, respectively, of BMS-955176 on Day 1.

  19. Apparent Total Body Clearance: Part A and C [ Time Frame: Baseline (Day 1) to Day 10 ]
    Apparent total body clearance was derived by non-compartmental methods, using a validated pharmacokinetic (PK) analysis program: KineticaTM 5.0 within eToolbox (version 2.7).

  20. Degree of Fluctuation (DF): Part A and C [ Time Frame: Baseline (Day 1) to Day 10 ]
    DF was calculated as the difference between Cmax and Cmin divided by Css-avg. DF was derived by non-compartmental methods, using a validated pharmacokinetic (PK) analysis program: KineticaTM 5.0 within eToolbox (version 2.7).

  21. Average Observed Plasma Concentration at Steady State (Css-avg): Part A and C [ Time Frame: Baseline (Day 1) to Day 10 ]
    Css-avg was calculated by the quotient of AUC(TAU) and the dosing interval (24 h). Css-avg was derived by non-compartmental methods, using a validated pharmacokinetic (PK) analysis program: KineticaTM 5.0 within eToolbox (version 2.7).

  22. Plasma Half-life: Part A and C [ Time Frame: Baseline (Day 1) to Day 10 ]
    Half-life of the terminal log-linear phase, (T-half), was calculated as natural logarithm of 2 (ln2)/λ, where λ is the absolute value of the slope of the terminal log-linear phase. T-half was derived by non-compartmental methods, using a validated pharmacokinetic (PK) analysis program: KineticaTM 5.0 within eToolbox (version 2.7).

  23. Number of Participants With Clinically Significant Grade 3/4 Laboratory Abnormalities From Baseline [ Time Frame: Day 1 to up to end of the study (Day 42) ]
    Laboratory abnormalities were determined and graded using the Division of Acquired Immune Deficiency Syndrome (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, version 1.0, December 2004.

  24. Number of Participants With Clinically Significant Changes in Heart Rate [ Time Frame: Day 1 to end of the study (Day 42) ]
    Heart rate was measured after the participants had been seated quietly for at least 5 minutes. Criteria used to determine heart rate that are outside of a pre-specified range, where changes from Baseline are based on matched postural positions and are calculated as parameter value - Baseline parameter value: Value >100 and change from Baseline > 30, or Value < 55 and change from Baseline < -15.

  25. Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) [ Time Frame: Day 1 to end of the study (Day 42) ]
    Participants with out of range ECG intervals were summarized. Criteria used to determine ECG results that are outside of a pre-specified range: PR (milliseconds [msec]): Value >200; QRS (msec): Value >120; QT (msec): Value >500 or change from Baseline >30; corrected QT interval Fridericia's formula (QTcF) (msec): Value >450 or change from Baseline >30.

  26. Number of Participants With Abnormal Changes in Physical Examination [ Time Frame: Day 1 to end of the study (Day 42) ]
    Participants with abnormal changes in physical examination is presented.

  27. Number of Participants With Clinically Significant Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) [ Time Frame: Day 1 to end of the study (Day 42) ]
    Systolic BP (millimeter of mercury [mmHg]): value >140 and change from Baseline >20, or value <90 and change from Baseline <-20; Diastolic BP (mmHg): value >90 and change from Baseline >10, or value <55 and change from Baseline <-10.



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.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
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

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): NCT01803074


Locations
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Germany
GSK Investigational Site
Berlin, Germany, 13353
Sponsors and Collaborators
ViiV Healthcare
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials ViiV Healthcare
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01803074    
Other Study ID Numbers: 206739
2012-004124-38 ( EudraCT Number )
AI468-002 ( Other Identifier: Bristol-Myers Squibb )
First Posted: March 4, 2013    Key Record Dates
Results First Posted: November 25, 2019
Last Update Posted: November 25, 2019
Last Verified: November 2019
Additional relevant MeSH terms:
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Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Atazanavir Sulfate
Tenofovir
Emtricitabine
BMS-955176
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors