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Clinical Trials

MainTitle

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

This study has been completed
Sponsor
ViiV Healthcare

Collaborator
GlaxoSmithKline

Information provided by (Responsible Party)
ViiV Healthcare
ClinicalTrials.gov Identifier
NCT01803074

First received: March 1, 2013
Last updated: January 19, 2017
Last Verified: January 2017
History of Changes
Purpose

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
Infection, Human Immunodeficiency Virus

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
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

Further study details as provided by ViiV Healthcare:

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 ]
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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]

Enrollment: 107
Study Start Date: April 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

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

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

Eligibility

Ages Eligible for Study: 18 Years to 55 Years  
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

contacts and locations

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
GSK Investigational Site
Berlin, Germany, 13353

Sponsors and Collaborators

ViiV Healthcare
GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials ViiV Healthcare
More Information

More Information

Additional Information:

BMS clinical trial educational resource

Additional Information:

FDA Safety Alerts and Recalls

Additional Information:

BMS Clinical Trial Information

Additional Information:

Investigator Inquiry form

Responsible Party: ViiV Healthcare  
ClinicalTrials.gov Identifier: NCT01803074   History of Changes  
Other Study ID Numbers: 206739  
  2012-004124-38  
  AI468-002  
Study First Received: March 1, 2013  
Last Updated: January 19, 2017  

Additional relevant MeSH terms:
Infection
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Ritonavir
Atazanavir Sulfate
Tenofovir
Emtricitabine

ClinicalTrials.gov processed this data on October 18, 2017
This information is provided by ClinicalTrials.gov.