Dose Ranging Study of GSK1265744 Plus Nucleoside Reverse Transcriptase Inhibitors for Induction of Human Immunodeficiency Virus-1 (HIV-1) Virologic Suppression Followed by Virologic Suppression Maintenance by GSK1265744 Plus Rilpivirine

Summary

The study is designed to select a dose of GSK1265744 primarily on the basis of antiviral activity and tolerability in HIV-1 infected, antiretroviral naive subjects.

This study consists of two parts:

Induction Phase: Approximately 200 subjects will be randomized (50 subjects in each of the 4 treatment arms). The Induction Phase consists of a 24 week dose-ranging evaluation of GSK1265744 at blinded doses of 10 mg, 30 mg and 60 mg once-daily and a control arm of open-label efavirenz (EFV) 600 mg once daily. The background dual nucleoside reverse transcriptase inhibitor (NRTI) antiretroviral therapy (ART) for all arms will be either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) as selected by the Investigator. Subjects randomized to a GSK1265744 containing arm, who successfully complete 24 weeks on study and demonstrate virologic suppression (defined as having a plasma HIV-1 ribonucleic acid \[RNA\] \<50 copies per milliliter \[c/mL\] before Week 24, with no signs of virologic rebound) will become eligible for the Maintenance Phase of this study.

Maintenance Phase: The background NRTIs will be discontinued and the subjects will continue their randomized dose of GSK1265744 in combination with rilpivirine (RPV) 25 mg once-daily for an additional 72 weeks. The Maintenance phase will evaluate the ability of this two drug ART regimen to maintain virologic suppression through Week 48, Week 72 and Week 96. Subjects randomized to the EFV arm will continue on their randomized regimen through Week 96.

After completion of the maintenance phase, subjects could enroll in the Open-Label Phase to continue GSK1265744 + RPV treatment as long as they continue to derive clinical benefit and until it is locally approved and commercially available.

Conditions

• Infection, Human Immunodeficiency Virus
• HIV Infections

Interventions

DRUG

GSK1265744 10 mg

GSK1265744 10 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

DRUG

GSK1265744 30 mg

GSK1265744 30 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

DRUG

GSK1265744 60 mg

GSK1265744 60 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase of the study and in combination with Rilpivirine 25 mg in the Maintenance Phase of the study.

DRUG

Efavirenz 600 mg

Efavirenz 600 mg will be administered orally once daily in combination with investigator-selected background NRTIs in the Induction Phase and Maintenance Phase of the study.

DRUG

Rilpivirine 25 mg

Rilpivirine 25 mg will be administered orally once daily in combination with GSK1265744 10 mg, 30 mg and 60 mg in the Maintenance Phase of the study.

DRUG

Placebo

Placebo matching to GSK1265744 will be administered along with GSK1265744 10 mg and 30 mg in the Induction phase and Maintenance phase of the study.

DRUG

Abacavir/Lamivudine (ABC/3TC) or Tenofovir/Emtricitabine (TDF/FTC)

The background dual NRTI therapy for all arms in the Induction Phase and Efavirenz 600 mg arm in the Maintenance Phase will be either abacavir 600 mg + lamivudine 300 mg (ABC/3TC) or tenofovir 300 mg + emtricitabine 200 mg (TDF/FTC) as selected by the Investigator.

Sponsors & Collaborators

• GlaxoSmithKline

  collaborator INDUSTRY

• ViiV Healthcare

  lead INDUSTRY

Principal Investigators

• GSK Clinical Trials · ViiV Healthcare

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2012-08-06

Primary Completion

2013-10-10

Completion

2019-01-15

Countries

• United States
• Canada

Study Locations