A Trial Comparing GSK1349572 50mg Plus Abacavir/Lamivudine Once Daily to Atripla (Also Called The SINGLE Trial) - Full Text View

Purpose

The purpose of this trial is to assess the non-inferior antiviral activity of GSK1349572 50 mg plus Abacavir/Lamivudine once daily versus Efavirenz/Emtricitabine/Tenofovir disoproxil fumarate (ATRIPLA® a trade mark of Bristol-Myers Squibb and Gilead Sciences LLC) over 48 weeks; non-inferiority will also be tested at Week 96. This study will be conducted in HIV-1 infected ART-naïve adult subjects. Long term antiviral activity, tolerability, safety, and development of viral resistance will be evaluated.

Condition	Intervention	Phase
Infection, Human Immunodeficiency Virus I	Drug: Dolutegravir Drug: Atripla Drug: Abacavir/Lamivudine Drug: Abacavir/Lamivudine Placebo Drug: Dolutegravir placebo Drug: Atripla placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Randomized, Double-Blind Study of the Safety and Efficacy of GSK1349572 Plus Abacavir/Lamivudine Fixed-Dose Combination Therapy Administered Once Daily Compared to Atripla Over 96 Weeks in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Lamivudine Abacavir Abacavir sulfate Atripla

U.S. FDA Resources

Further study details as provided by ViiV Healthcare:

Primary Outcome Measures:

The primary efficacy endpoint is the proportion of subjects achieving and maintaining confirmed HIV-1 RNA less than 50 copies/mL through Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate the efficacy of the treatment arms over time using proportions of subjects maintaining plasma HIV-1 RNA <50copies/mL to Week 96 as well as change from baseline in HIV-1 RNA and increases in CD4+ cell counts [ Time Frame: 48 and 96 weeks ] [ Designated as safety issue: No ]
To evaluate the number of participants with clinical or laboratory adverse events as a measure of safety and tolerability of the two treatment arms [ Time Frame: 48 and 96 Weeks ] [ Designated as safety issue: No ]
To assess the development of viral resistance in subjects experiencing virological failure. [ Time Frame: 48 and 96 Weeks ] [ Designated as safety issue: No ]
To evaluate the incidence of HIV-associated conditions. [ Time Frame: 48 and 96 Weeks ] [ Designated as safety issue: No ]

Enrollment:	788
Study Start Date:	February 2011
Estimated Study Completion Date:	March 2015
Primary Completion Date:	September 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Dolutegravir (N=~394): Dolutegravir 50mg once daily + abacavir/lamivudine as the fixed-dose combination once daily + Atripla placebo once daily	Drug: Dolutegravir Dolutegravir (also known as GSK1349572) 50 mg taken once daily Drug: Abacavir/Lamivudine taken once daily; also known as EPZICOM Drug: Atripla placebo matching placebo taken once daily on an empty stomach
Active Comparator: Atripla (N=~394): Atripla once daily + Dolutegravir placebo once daily + abacavir/lamivudine as the fixed-dose combination placebo once daily	Drug: Atripla Atripla once daily on an empty stomach Drug: Abacavir/Lamivudine Placebo matching placebo taken once daily Drug: Dolutegravir placebo matching placebo taken once daily

Detailed Description:

ING114467 is a Phase 3 randomized, double-blind, double dummy, active-controlled, multicenter, study conducted in approximately 788 HIV-1 infected ART-naïve subjects. Subjects will be randomized 1:1 one of the following treatment arms:

GSK1349572 50 mg plus abacavir/lamivudine fixed-dose combination once daily (approximately 394 subjects)

OR

Atripla once daily (approximately 394 subjects)

Analyses will be conducted at 48 weeks and 96 weeks. Subjects randomized to receive GSK1349572 and who successfully complete 96 weeks of treatment will continue to have access to GSK1349572 plus abacavir/lamivudine fixed-dose combination through the study until it is locally available-as long as they continue to derive clinical benefit, until they meet a protocol-defined reason for discontinuation, or until development of the compound is terminated.

ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Screening plasma HIV-1 RNA ≥1000 c/mL
Antiretroviral-naïve (≤ 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection)
Ability to understand and sign a written informed consent form
Willingness to use approved methods of contraception to avoid pregnancy (women of child bearing potential only)
Age equal to or greater than 18 years
A negative HLAB*5701 allele assessment

Exclusion Criteria:

Women who are pregnant or breastfeeding;
Active Center for Disease and Prevention Control (CDC) Category C disease
Hepatic impairment
HBV co-infection
Anticipated need for HCV therapy during the study
Allergy or intolerance to the study drugs or their components or drugs of their class
Malignancy within the past 5 years
Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any immunomodulator within 28 days of Screening
Exposure to an agent with documented activity against HIV-1 in vitro or an experimental vaccine or drug within 28 days of first dose of study medication
Primary viral resistance in the Screening result
Verified Grade 4 laboratory abnormality
ALT >5 xULN
ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin);
Estimated creatinine clearance <50 mL/min
Recent history (≤3 months) of upper or lower gastrointestinal bleed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01263015

Show 133 Study Locations

Sponsors and Collaborators

ViiV Healthcare

Shionogi

GlaxoSmithKline

Investigators

Study Director:

GSK Clinical Trials

ViiV Healthcare

More Information

No publications provided

Responsible Party:	ViiV Healthcare
ClinicalTrials.gov Identifier:	NCT01263015 History of Changes
Other Study ID Numbers:	114467
Study First Received:	December 16, 2010
Last Updated:	April 18, 2013
Health Authority:	Spain: Agencia Espanola de Medicamentos y Productos Sanitarios Italy: Comitato Etico Fondazione Centro San Raffaele del Monte Tabor - Via Olgettina, 60 - 20132 Milano Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Belgium: Federal Agency for Medicines and Health Products United Kingdom: Medicines and Healthcare Products Regulatory Agency United States: Food and Drug Administration Hungary: Országos Gyógyszerészeti Intézet South Africa: Medicines Control Council Germany: Bundesinstitut für Arzneimittel und Medizinprodukte Romania: National Medicines Agency Denmark: Danish Medicines Agency France: Agence Française de Sécurité Sanitaire des Produits de Santé Canada: Health Canada Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Australia: Therapeutic Goods Administration

Keywords provided by ViiV Healthcare:

GSK1349572
Abacavir/Lamivudine
Treatment-naive
HIV Infection

Dolutegravir
integrase inhibitor
Atripla

Additional relevant MeSH terms:

Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Lamivudine
Abacavir

Efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination
Integrase Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on May 22, 2013