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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01803074
First received: March 1, 2013
Last updated: October 30, 2014
Last verified: February 2014

March 1, 2013
October 30, 2014
March 2013
December 2014   (final data collection date for primary outcome measure)
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 ]
Change in plasma HIV-1 RNA levels from baseline 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 ]
Complete list of historical versions of study NCT01803074 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 (Parts A and C) or up to Day 42 (Part B) ] [ Designated as safety issue: Yes ]
  • Time course of HIV-1 RNA level change [ Time Frame: Baseline (Day 1), up to Day 24 (Parts A and C) , up to Day 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 Atazanavir (ATV)+/-Ritonavir (RTV) in HIV-1 infected subjects [ Time Frame: Baseline (Day 1), up to Day 24 (Parts A and C) , up to Day 42 (Part B) ] [ Designated as safety issue: No ]
  • Maximum observed plasma concentration (Cmax) [ Time Frame: 12 time points on Day 1 and Day 10 (Part A and C) and 9 time points on Day 28 (Part B) ] [ Designated as safety issue: No ]
  • Steady state trough concentration (Cmin) [ Time Frame: 12 time points on Day 1 and Day 10 (Part A and C) and 9 time points on Day 28 (Part B) ] [ Designated as safety issue: No ]
  • Time of maximum observed plasma concentration (Tmax) [ Time Frame: 12 time points on Day 1 and Day 10 (Part A and C) and 9 time points on Day 28 (Part B) ] [ Designated as safety issue: No ]
  • Trough observed plasma concentration (Ctrough) [ Time Frame: 12 time points on Day 1 and Day 10 (Part A and C) and 9 time points on Day 28 (Part B) ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve in one dosing interval [AUC(TAU)] [ Time Frame: 12 time points on Day 1 and Day 10 (Part A and C) and 9 time points on 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 [ Time Frame: 12 time points on Day 1 and Day 10 (Part A and C) and 9 time points on Day 28 (Part B) ] [ Designated as safety issue: No ]
  • Apparent total body clearance (CLT/F) [ Time Frame: 12 time points on Day 1 and Day 10 (Part A and C) and 9 time points on Day 28 (Part B) ] [ Designated as safety issue: No ]
  • Terminal Plasma half-life (T-Half)-after last dose only [ Time Frame: Day 10 (Part A and C) and Day 28 (Part B) ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study to Evaluate a HIV Drug for the Treatment of HIV Infection
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

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

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

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
HIV-1 Infection
  • Drug: BMS-955176
  • Drug: Placebo matching with BMS-955176
  • Drug: Atazanavir
  • Drug: Ritonavir
  • Drug: Tenofovir
  • Drug: Emtricitabine
  • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • 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

    Interventions:
    • Drug: BMS-955176
    • Drug: Placebo matching with BMS-955176
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
118
December 2014
December 2014   (final data collection date for primary outcome measure)

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
Both
18 Years to 55 Years
No
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.
Germany,   South Africa
 
NCT01803074
AI468-002, 2012-004124-38
No
Bristol-Myers Squibb
Bristol-Myers Squibb
Not Provided
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
Bristol-Myers Squibb
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP