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Completed

NCT Number: NCT01803074

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

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

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Key information

Conditions

Infection, Human Immunodeficiency Virus Acquired Immunodeficiency Syndrome Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Urogenital Diseases Virus Diseases

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

GSK Investigational Site

Berlin, 13353, Germany

About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BMS-955176

Drug

BMS-955176

Placebo matching with BMS-955176

Drug

Placebo matching with BMS-955176

Atazanavir

Drug

Atazanavir

Ritonavir

Drug

Ritonavir

Tenofovir

Drug

Tenofovir

Emtricitabine

Drug

Emtricitabine

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

ViiV Healthcare

Industry

Collaborators

  • GlaxoSmithKline

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2014
Study completion
2014
First posted
Mar 4, 2013
Registry last updated
Nov 25, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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