Clinical trial NCT01803074: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Infection, Human Immunodeficiency Virus
HIV Infections
Lead sponsor: ViiV Healthcare
Sponsor class: INDUSTRY
Collaborators: name: GlaxoSmithKline
First posted: 2013-03-04
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Change in Plasma Log10 HIV-1 Ribonucleic Acid (RNA) Levels From Baseline to Day 11
timeFrame: Baseline (Day 1) and Day 11 after the final dose with BMS-955176
Secondary outcomes:
measure: Time to Reach Maximum Plasma Concentration (Tmax) - Part A and C
timeFrame: Pre-dose Day 1 and Day 10
measure: 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
timeFrame: Day 1 to end of the study (Day 42)
measure: Maximum Decline From Baseline in Log10 HIV-1 RNA - Part A and C
timeFrame: Baseline (Day 1) up to Day 24
measure: Maximum Decline From Baseline in Log10 HIV-1 RNA - Part B
timeFrame: Baseline (Day 1) up to Day 42
measure: Time to Maximum Decline in Log 10 HIV-1 RNA - Part A and C
timeFrame: Baseline (Day 1) up to Day 24
measure: Time to Maximum Decline in Log 10 HIV-1 RNA - Part B
timeFrame: Baseline (Day 1) up to Day 42
measure: Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Counts - Part A and C
timeFrame: Baseline (Day 1) up to Day 24
measure: Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Counts - Part B
timeFrame: Baseline (Day 1) up to Day 42
measure: Percent Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Percent - Part A and C
timeFrame: Baseline (Day 1) up to Day 24
measure: Percent Change From Baseline in Cluster of Differentiation (CD) 4+ and CD8+ Lymphocyte Percent - Part B
timeFrame: Baseline (Day 1) up to Day 42
measure: Time to Reach Maximum Plasma Concentration (Tmax) - Part B
timeFrame: Pre-dose Day 1 and Day 28
measure: Maximum Observed Plasma Concentrations (Cmax) - Part A and C
timeFrame: Pre-dose Day 1 and Day 10
measure: Plasma Concentration 24 Hours Post-Dose (C24) - Part A and C
timeFrame: 24 hours post-dose
measure: Maximum Observed Plasma Concentrations (Cmax) - Part B
timeFrame: Pre-dose Day 1 and Day 28
measure: Plasma Concentration 24 Hours Post-Dose (C24) - Part B
timeFrame: 24 hours post-dose
measure: Area Under The Plasma Concentration - Time Curve Over the Dosing Interval (AUC([Tau]) - Part A and C
timeFrame: Pre-dose Day 1 and Day 10
measure: Area Under The Plasma Concentration - Time Curve Over the Dosing Interval (AUC[Tau]) - Part B
timeFrame: Pre-dose Day 1 and Day 28
measure: Accumulation Index (AI): Part A and C
timeFrame: Baseline and Day 10
measure: Apparent Total Body Clearance: Part A and C
timeFrame: Baseline (Day 1) to Day 10
measure: Degree of Fluctuation (DF): Part A and C
timeFrame: Baseline (Day 1) to Day 10
measure: Average Observed Plasma Concentration at Steady State (Css-avg): Part A and C
timeFrame: Baseline (Day 1) to Day 10
measure: Plasma Half-life: Part A and C
timeFrame: Baseline (Day 1) to Day 10
measure: Number of Participants With Clinically Significant Grade 3/4 Laboratory Abnormalities From Baseline
timeFrame: Day 1 to up to end of the study (Day 42)
measure: Number of Participants With Clinically Significant Changes in Heart Rate
timeFrame: Day 1 to end of the study (Day 42)
measure: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG)
timeFrame: Day 1 to end of the study (Day 42)
measure: Number of Participants With Abnormal Changes in Physical Examination
timeFrame: Day 1 to end of the study (Day 42)
measure: Number of Participants With Clinically Significant Changes in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
timeFrame: Day 1 to end of the study (Day 42)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: GSK Investigational Site
Study officials:
affiliation: ViiV Healthcare
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
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.