Back to resultsStudy to Evaluate a HIV Drug for the Treatment of HIV Infection
Primary Purpose
Infection, Human Immunodeficiency Virus, HIV Infections
Status
Completed
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
BMS-955176
Placebo matching with BMS-955176
Atazanavir
Ritonavir
Tenofovir
Emtricitabine
Sponsored by
About this trial
This is an interventional treatment trial for Infection, Human Immunodeficiency Virus
Eligibility 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
Sites / Locations
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Arm 11
Arm 12
Arm 13
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
Part A-Group 1: BMS-955176 (5 mg) or Placebo
Part A-Group 2: BMS-955176 (10 mg) or Placebo
Part A-Group 3: BMS-955176 (20 mg) or Placebo
Part A-Group 4: BMS-955176 (40 mg) or Placebo
Part B-Group 5: BMS-955176 + Atazanavir
Part B-Group 6: BMS-955176 + Atazanavir + Ritonavir
Part B-Group 7: Atazanavir+Ritonavir+Tenofovir+Emtricitabine
Part C-Group 8: BMS-955176 (40 mg) or Placebo
Part A-Group 9: BMS-955176 (80 mg) or Placebo
Part A-Group 10: BMS-955176 (120 mg) or Placebo
Part A-Group 11 (Optional): BMS-955176 (≤120 mg) or Placebo
Part B-Group 12: BMS-955176 (80 mg) + Atazanavir
Part C-Group 13: BMS-955176 (120 mg) or Placebo
Arm Description
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
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
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
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
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
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
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
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
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
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
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
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
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
Outcomes
Primary Outcome Measures
Change in Plasma Log10 HIV-1 Ribonucleic Acid (RNA) Levels From Baseline to Day 11
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
Time to Reach Maximum Plasma Concentration (Tmax) - Part A and C
Time to reach the maximum plasma concentration was directly determined from concentration time data.
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
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.
Maximum Decline From Baseline in Log10 HIV-1 RNA - Part A and C
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.
Maximum Decline From Baseline in Log10 HIV-1 RNA - Part B
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.
Time to Maximum Decline in Log 10 HIV-1 RNA - Part A and C
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.
Time to Maximum Decline in Log 10 HIV-1 RNA - Part B
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.
Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Counts - Part A and C
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.
Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Counts - Part B
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.
Percent Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Percent - Part A and C
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.
Percent Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Percent - Part B
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.
Time to Reach Maximum Plasma Concentration (Tmax) - Part B
Tmax was directly determined from concentration time data.
Maximum Observed Plasma Concentrations (Cmax) - Part A and C
Cmax was defined as the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Plasma Concentration 24 Hours Post-Dose (C24) - Part A and C
C24 was defined as the plasma concentration of BMS-955176 at 24 hours post-dose.
Maximum Observed Plasma Concentrations (Cmax) - Part B
Cmax was defined as the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Plasma Concentration 24 Hours Post-Dose (C24) - Part B
C24 was defined as the plasma concentration of BMS-955176 at 24 hours post-dose.
Area Under The Plasma Concentration - Time Curve Over the Dosing Interval (AUC([Tau]) - Part A and C
AUC(tau) was defined as the area under the plasma concentration - time curve over the dosing interval.
Area Under The Plasma Concentration - Time Curve Over the Dosing Interval (AUC[Tau]) - Part B
AUC(tau) was defined as the area under the plasma concentration - time curve over the dosing interval.
Accumulation Index (AI): Part A and C
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.
Apparent Total Body Clearance: Part A and C
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).
Degree of Fluctuation (DF): Part A and C
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).
Average Observed Plasma Concentration at Steady State (Css-avg): Part A and C
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).
Plasma Half-life: Part A and C
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).
Number of Participants With Clinically Significant Grade 3/4 Laboratory Abnormalities From Baseline
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.
Number of Participants With Clinically Significant Changes in Heart Rate
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.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
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.
Number of Participants With Abnormal Changes in Physical Examination
Participants with abnormal changes in physical examination is presented.
Number of Participants With Clinically Significant Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
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.
Full Information
NCT ID
NCT01803074
First Posted
March 1, 2013
Last Updated
November 4, 2019
Sponsor
ViiV Healthcare
Collaborators
GlaxoSmithKline
1. Study Identification
Unique Protocol Identification Number
NCT01803074
Brief Title
Study to Evaluate a HIV Drug for the Treatment of HIV Infection
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
April 4, 2013 (Actual)
Primary Completion Date
November 29, 2014 (Actual)
Study Completion Date
November 29, 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ViiV Healthcare
Collaborators
GlaxoSmithKline
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infection, Human Immunodeficiency Virus, HIV Infections
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
107 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Part A-Group 1: BMS-955176 (5 mg) or Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Part A-Group 2: BMS-955176 (10 mg) or Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Part A-Group 3: BMS-955176 (20 mg) or Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Part A-Group 4: BMS-955176 (40 mg) or Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Part B-Group 5: BMS-955176 + Atazanavir
Arm Type
Experimental
Arm Description
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
Arm Title
Part B-Group 6: BMS-955176 + Atazanavir + Ritonavir
Arm Type
Experimental
Arm Description
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
Arm Title
Part B-Group 7: Atazanavir+Ritonavir+Tenofovir+Emtricitabine
Arm Type
Experimental
Arm Description
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
Arm Title
Part C-Group 8: BMS-955176 (40 mg) or Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Part A-Group 9: BMS-955176 (80 mg) or Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Part A-Group 10: BMS-955176 (120 mg) or Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Part A-Group 11 (Optional): BMS-955176 (≤120 mg) or Placebo
Arm Type
Experimental
Arm Description
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
Arm Title
Part B-Group 12: BMS-955176 (80 mg) + Atazanavir
Arm Type
Experimental
Arm Description
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
Arm Title
Part C-Group 13: BMS-955176 (120 mg) or Placebo
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
BMS-955176
Intervention Description
BMS-955176
Intervention Type
Drug
Intervention Name(s)
Placebo matching with BMS-955176
Intervention Description
Placebo matching with BMS-955176
Intervention Type
Drug
Intervention Name(s)
Atazanavir
Intervention Description
Atazanavir
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Description
Ritonavir
Intervention Type
Drug
Intervention Name(s)
Tenofovir
Intervention Description
Tenofovir
Intervention Type
Drug
Intervention Name(s)
Emtricitabine
Intervention Description
Emtricitabine
Primary Outcome Measure Information:
Title
Change in Plasma Log10 HIV-1 Ribonucleic Acid (RNA) Levels From Baseline to Day 11
Description
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.
Time Frame
Baseline (Day 1) and Day 11 after the final dose with BMS-955176
Secondary Outcome Measure Information:
Title
Time to Reach Maximum Plasma Concentration (Tmax) - Part A and C
Description
Time to reach the maximum plasma concentration was directly determined from concentration time data.
Time Frame
Pre-dose Day 1 and Day 10
Title
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
Description
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.
Time Frame
Day 1 to end of the study (Day 42)
Title
Maximum Decline From Baseline in Log10 HIV-1 RNA - Part A and C
Description
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.
Time Frame
Baseline (Day 1) up to Day 24
Title
Maximum Decline From Baseline in Log10 HIV-1 RNA - Part B
Description
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.
Time Frame
Baseline (Day 1) up to Day 42
Title
Time to Maximum Decline in Log 10 HIV-1 RNA - Part A and C
Description
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.
Time Frame
Baseline (Day 1) up to Day 24
Title
Time to Maximum Decline in Log 10 HIV-1 RNA - Part B
Description
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.
Time Frame
Baseline (Day 1) up to Day 42
Title
Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Counts - Part A and C
Description
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.
Time Frame
Baseline (Day 1) up to Day 24
Title
Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Counts - Part B
Description
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.
Time Frame
Baseline (Day 1) up to Day 42
Title
Percent Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Percent - Part A and C
Description
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.
Time Frame
Baseline (Day 1) up to Day 24
Title
Percent Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Percent - Part B
Description
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.
Time Frame
Baseline (Day 1) up to Day 42
Title
Time to Reach Maximum Plasma Concentration (Tmax) - Part B
Description
Tmax was directly determined from concentration time data.
Time Frame
Pre-dose Day 1 and Day 28
Title
Maximum Observed Plasma Concentrations (Cmax) - Part A and C
Description
Cmax was defined as the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time Frame
Pre-dose Day 1 and Day 10
Title
Plasma Concentration 24 Hours Post-Dose (C24) - Part A and C
Description
C24 was defined as the plasma concentration of BMS-955176 at 24 hours post-dose.
Time Frame
24 hours post-dose
Title
Maximum Observed Plasma Concentrations (Cmax) - Part B
Description
Cmax was defined as the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.
Time Frame
Pre-dose Day 1 and Day 28
Title
Plasma Concentration 24 Hours Post-Dose (C24) - Part B
Description
C24 was defined as the plasma concentration of BMS-955176 at 24 hours post-dose.
Time Frame
24 hours post-dose
Title
Area Under The Plasma Concentration - Time Curve Over the Dosing Interval (AUC([Tau]) - Part A and C
Description
AUC(tau) was defined as the area under the plasma concentration - time curve over the dosing interval.
Time Frame
Pre-dose Day 1 and Day 10
Title
Area Under The Plasma Concentration - Time Curve Over the Dosing Interval (AUC[Tau]) - Part B
Description
AUC(tau) was defined as the area under the plasma concentration - time curve over the dosing interval.
Time Frame
Pre-dose Day 1 and Day 28
Title
Accumulation Index (AI): Part A and C
Description
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.
Time Frame
Baseline and Day 10
Title
Apparent Total Body Clearance: Part A and C
Description
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).
Time Frame
Baseline (Day 1) to Day 10
Title
Degree of Fluctuation (DF): Part A and C
Description
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).
Time Frame
Baseline (Day 1) to Day 10
Title
Average Observed Plasma Concentration at Steady State (Css-avg): Part A and C
Description
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).
Time Frame
Baseline (Day 1) to Day 10
Title
Plasma Half-life: Part A and C
Description
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).
Time Frame
Baseline (Day 1) to Day 10
Title
Number of Participants With Clinically Significant Grade 3/4 Laboratory Abnormalities From Baseline
Description
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.
Time Frame
Day 1 to up to end of the study (Day 42)
Title
Number of Participants With Clinically Significant Changes in Heart Rate
Description
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.
Time Frame
Day 1 to end of the study (Day 42)
Title
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
Description
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.
Time Frame
Day 1 to end of the study (Day 42)
Title
Number of Participants With Abnormal Changes in Physical Examination
Description
Participants with abnormal changes in physical examination is presented.
Time Frame
Day 1 to end of the study (Day 42)
Title
Number of Participants With Clinically Significant Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
Description
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.
Time Frame
Day 1 to end of the study (Day 42)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
ViiV Healthcare
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Berlin
ZIP/Postal Code
13353
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
28369211
Citation
Hwang C, Schurmann D, Sobotha C, Boffito M, Sevinsky H, Ray N, Ravindran P, Xiao H, Keicher C, Huser A, Krystal M, Dicker IB, Grasela D, Lataillade M. Antiviral Activity, Safety, and Exposure-Response Relationships of GSK3532795, a Second-Generation Human Immunodeficiency Virus Type 1 Maturation Inhibitor, Administered as Monotherapy or in Combination With Atazanavir With or Without Ritonavir in a Phase 2a Randomized, Dose-Ranging, Controlled Trial (AI468002). Clin Infect Dis. 2017 Aug 1;65(3):442-452. doi: 10.1093/cid/cix239.
Results Reference
derived
Links:
URL
http://www.bms.com/studyconnect/Pages/home.aspx
Description
BMS clinical trial educational resource
Learn more about this trial
Study to Evaluate a HIV Drug for the Treatment of HIV Infection
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