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

NCT01803074 | Completed Phase 2 Results

• 3 other identifiers: 2067392012-004124-38AI468-002
• Study Type: interventional
• Target: 107
• Locations: 1 country
• Sites: 1

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

Conditions

Infection, Human Immunodeficiency Virus; HIV Infections

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline (Day 1) and Day 11 after the final dose with BMS-955176

Secondary Outcomes (27)

• Time to Reach Maximum Plasma Concentration (Tmax) - Part A and C

  Pre-dose Day 1 and Day 10

• 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

  Day 1 to end of the study (Day 42)

• Maximum Decline From Baseline in Log10 HIV-1 RNA - Part A and C

  Baseline (Day 1) up to Day 24

• Maximum Decline From Baseline in Log10 HIV-1 RNA - Part B

  Baseline (Day 1) up to Day 42

• Time to Maximum Decline in Log 10 HIV-1 RNA - Part A and C

  Baseline (Day 1) up to Day 24

Study Arms (13)

Part A-Group 1: BMS-955176 (5 mg) or Placebo

EXPERIMENTAL

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

Part A-Group 2: BMS-955176 (10 mg) or Placebo

EXPERIMENTAL

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

Part A-Group 3: BMS-955176 (20 mg) or Placebo

EXPERIMENTAL

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

Part A-Group 4: BMS-955176 (40 mg) or Placebo

EXPERIMENTAL

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

Part B-Group 5: BMS-955176 + Atazanavir

EXPERIMENTAL

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

Part B-Group 6: BMS-955176 + Atazanavir + Ritonavir

EXPERIMENTAL

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

Part B-Group 7: Atazanavir+Ritonavir+Tenofovir+Emtricitabine

EXPERIMENTAL

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

Part C-Group 8: BMS-955176 (40 mg) or Placebo

EXPERIMENTAL

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

Part A-Group 9: BMS-955176 (80 mg) or Placebo

EXPERIMENTAL

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

Part A-Group 10: BMS-955176 (120 mg) or Placebo

EXPERIMENTAL

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

Part A-Group 11 (Optional): BMS-955176 (≤120 mg) or Placebo

EXPERIMENTAL

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

Part B-Group 12: BMS-955176 (80 mg) + Atazanavir

EXPERIMENTAL

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

Part C-Group 13: BMS-955176 (120 mg) or Placebo

EXPERIMENTAL

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

Interventions

BMS-955176 DRUG

BMS-955176

Part A-Group 10: BMS-955176 (120 mg) or Placebo; Part A-Group 11 (Optional): BMS-955176 (≤120 mg) or Placebo; 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 A-Group 9: BMS-955176 (80 mg) or Placebo; Part B-Group 12: BMS-955176 (80 mg) + Atazanavir; Part B-Group 5: BMS-955176 + Atazanavir; Part B-Group 6: BMS-955176 + Atazanavir + Ritonavir; Part C-Group 13: BMS-955176 (120 mg) or Placebo; Part C-Group 8: BMS-955176 (40 mg) or Placebo

Placebo matching with BMS-955176 DRUG

Placebo matching with BMS-955176

Part A-Group 10: BMS-955176 (120 mg) or Placebo; Part A-Group 11 (Optional): BMS-955176 (≤120 mg) or Placebo; 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 A-Group 9: BMS-955176 (80 mg) or Placebo; Part C-Group 13: BMS-955176 (120 mg) or Placebo; Part C-Group 8: BMS-955176 (40 mg) or Placebo

Atazanavir DRUG

Atazanavir

Part B-Group 12: BMS-955176 (80 mg) + Atazanavir; Part B-Group 5: BMS-955176 + Atazanavir; Part B-Group 6: BMS-955176 + Atazanavir + Ritonavir; Part B-Group 7: Atazanavir+Ritonavir+Tenofovir+Emtricitabine

Ritonavir DRUG

Ritonavir

Part B-Group 6: BMS-955176 + Atazanavir + Ritonavir; Part B-Group 7: Atazanavir+Ritonavir+Tenofovir+Emtricitabine

Tenofovir DRUG

Tenofovir

Part B-Group 7: Atazanavir+Ritonavir+Tenofovir+Emtricitabine

Emtricitabine DRUG

Emtricitabine

Part B-Group 7: Atazanavir+Ritonavir+Tenofovir+Emtricitabine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

GSK Investigational Site

Berlin, 13353, Germany

Location

Related Publications (1)

• 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.

  PMID: 28369211 DERIVED

Related Links

• BMS clinical trial educational resource
• Investigator Inquiry form

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

BMS-955176; Atazanavir Sulfate; Ritonavir; Tenofovir; Emtricitabine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2013
• First Posted: March 4, 2013
• Study Start: April 4, 2013
• Primary Completion: November 29, 2014
• Study Completion: November 29, 2014
• Last Updated: November 25, 2019
• Results First Posted: November 25, 2019

Record last verified: 2019-11

Locations

DE (1)