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: June 12, 2014
Last verified: February 2014
  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
HIV-1 Infection
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
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

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 ] [ Designated as safety issue: No ]

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) ] [ 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 ]

Estimated Enrollment: 118
Study Start Date: March 2013
Estimated Study Completion Date: November 2014
Estimated 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 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

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

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

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

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

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

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

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

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

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

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

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

Drug: BMS-955176 Drug: 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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
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
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

Contacts
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 #.

Locations
Germany
Local Institution Recruiting
Berlin, Germany, 10117
Contact: Site 0001         
South Africa
Local Institution Not yet recruiting
Pretoria, Gauteng, South Africa, 0087
Contact: Site 0003         
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01803074     History of Changes
Other Study ID Numbers: AI468-002, 2012-004124-38
Study First Received: March 1, 2013
Last Updated: June 12, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Ritonavir
Atazanavir
Tenofovir
Tenofovir disoproxil
Emtricitabine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014