Dolutegravir Compared to Darunavir/Ritonavir , Each in Combination With Dual Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in ART-naive Subjects

NCT ID: NCT01449929

Last Updated: 2018-01-16

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

488 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-10-31

Study Completion Date

2016-12-26

Brief Summary

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This study will be conducted in approximately 468 HIV-1 infected antiretroviral therapy (ART)-naïve subjects. Subjects will be randomized 1:1 to receive dolutegravir (DTG) 50 mg once daily (approximately 234 subjects) or darunavir/ritonavir (DRV/r) 800 mg/100 mg once daily (approximately 234 subjects), each in combination with fixed-dose dual nucleoside reverse transriptase inhibitor (NRTI) therapy (either abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). Subjects will be stratified by screening HIV-1 RNA and background NRTI selection. The primary analysis will take place after the last subject completes 48 weeks on therapy; an additional analysis will be conducted after the last subject completes Week 96 on study.

Detailed Description

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ING114915 is a Phase IIIb randomized, open-label, active-controlled, multicentre, parallel group, fully-powered non-inferiority study. The study will be conducted in approximately 468 HIV-1 infected ART-naïve subjects. Subjects will be randomized 1:1 to receive DTG 50 mg once daily (approximately 234 subjects) or DRV/r 800 mg/100 mg once daily (approximately 234 subjects), each in combination with fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC). The primary analysis will take place after the last subject completes 48 weeks on therapy; an additional analysis will be conducted after the last subject completes Week 96 on study.

Subjects who fulfil eligibility requirements will be randomized 1:1 to receive DTG 50 mg once daily or DRV/r 800 mg/100 mg once daily. In order to achieve balance across the two treatment groups of the study, randomization will be stratified by: screening plasma HIV-1 RNA \>/ 100,000 copies/mL (c/mL) or \> 100,000 c/mL and background dual NRTI (ABC/3TC or TDF/FTC) The DTG and DRV/r doses will be administered in an open-label fashion throughout the study.

Subjects randomized to receive DTG and who successfully complete 96 weeks of treatment will continue to have access to DTG until either it is locally approved and commercially available, the patient no longer derives clinical benefit, the patient meets a protocol-defined reason for discontinuation or until development of DTG is terminated. Subjects randomized to the DRV/r arm will receive DRV/r through their Week 96 visit, after which they will be discontinued from the study and will need to make alternative arrangements to access antiretroviral medication. All subjects will receive background dual-NRTI therapy through their Week 96 visit.

Conditions

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Infection, Human Immunodeficiency Virus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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dolutegravir 50mg once daily (OAD)

in combination with either abacavir/lamivudine fixed dose combination tablet OAD or tenofovir disoproxil fumarate/emtricitabline fixed dose combination tablet OAD

Group Type EXPERIMENTAL

dolutegravir 50 mg OAD

Intervention Type DRUG

1 x 50 mg tablet OAD

darunavir 800mg OAD in combination with ritonavir 100mg OAD

in combination with either abacavir/lamivudine fixed dose combination tablet OAD or tenofovir disoproxil fumarate/emtricitabline fixed dose combination tablet OAD

Group Type ACTIVE_COMPARATOR

darunavir 800mg OAD

Intervention Type DRUG

2 x 400mg tablets OAD

ritonavir 100mg OAD

Intervention Type DRUG

1 x 100mg tablet OAD

Interventions

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dolutegravir 50 mg OAD

1 x 50 mg tablet OAD

Intervention Type DRUG

darunavir 800mg OAD

2 x 400mg tablets OAD

Intervention Type DRUG

ritonavir 100mg OAD

1 x 100mg tablet OAD

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* HIV-1 infected adults greater than or equal to 18 years of age. Females are eligible to enter and participate in the study if she is (1) non-childbearing potential, (2) child bearing potential with negative pregnancy test at screening and Day 1 and agrees to use protocol-specified methods of birth control while on study.
* HIV-1 infection with a screening plasma HIV-1 RNA greater than or equal to 1000copies/mL
* Antiretroviral-naïve (less than or equal to 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection)
* Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening

Exclusion Criteria

* Women who are pregnant or breastfeeding
* Any evidence of an active Centers for Disease and Prevention Control (CDC) Category C disease \[CDC, 1993\], except cutaneous Kaposi's sarcoma not requiring systemic therapy
* Subjects with moderate to severe hepatic impairment (Class B or C) as determined by Child-Pugh classification
* Anticipated need for Hepatitis C virus (HCV) therapy during the study
* History or presence of allergy or intolerance to the study drugs or their components or drugs of their class
* History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the subject
* Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
* Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators
* Treatment with any agent, except recognized ART as allowed above, with documented activity against HIV-1 in vitro within 28 days of first dose of investigational product
* Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product
* Any evidence of primary viral resistance based on the presence of any major resistance-associated mutation \[IAS-USA, 2010\] in the Screening result or, if known, any historical resistance test result
* Any verified Grade 4 laboratory abnormality. Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound is exclusionary
* Alanine aminotransferase (ALT) greater than 5 times the upper limit of normal
* ALT greater than 3 times the upper limit of normal and bilirubin greater than or equal to 1.5 times the upper limit of normal (with greater than 35% direct bilirubin)
* Subject has creatinine clearance of less than 50 mL/min via Cockroft-Gault method
* Recent history (less than or equal to 3 months) of any upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

ViiV Healthcare

Locations

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GSK Investigational Site

Birmingham, Alabama, United States

Site Status

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Los Angeles, California, United States

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Los Angeles, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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Norwalk, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Washington D.C., District of Columbia, United States

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Washington D.C., District of Columbia, United States

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Daytona Beach, Florida, United States

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Orlando, Florida, United States

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Tampa, Florida, United States

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Vero Beach, Florida, United States

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Augusta, Georgia, United States

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Decatur, Georgia, United States

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Macon, Georgia, United States

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Savannah, Georgia, United States

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Springfield, Massachusetts, United States

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Detroit, Michigan, United States

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Minneapolis, Minnesota, United States

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Kansas City, Missouri, United States

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Chapel Hill, North Carolina, United States

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Charlotte, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cincinnati, Ohio, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Providence, Rhode Island, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Longview, Texas, United States

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Seattle, Washington, United States

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Montpellier, , France

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Nantes, , France

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Paris, , France

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Paris, , France

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Paris, , France

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Saint-Denis, , France

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Freiburg im Breisgau, Baden-Wurttemberg, Germany

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Frankfurt am Main, Hesse, Germany

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Hamburg, , Germany

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Modena, Emilia-Romagna, Italy

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Rome, Lazio, Italy

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Milan, Lombardy, Italy

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Milan, Lombardy, Italy

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Turin, Piedmont, Italy

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Ponce, , Puerto Rico

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San Juan, , Puerto Rico

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San Juan, , Puerto Rico

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Bucharest, , Romania

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Bucharest, , Romania

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Constanța, , Romania

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Krasnodar, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Saratov, , Russia

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Volgograd, , Russia

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Badalona, , Spain

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Barcelona, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Seville, , Spain

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Bern, , Switzerland

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Lausanne, , Switzerland

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Zurich, , Switzerland

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Countries

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United States France Germany Italy Puerto Rico Romania Russia Spain Switzerland

References

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Molina JM, Clotet B, van Lunzen J, Lazzarin A, Cavassini M, Henry K, Kulagin V, Givens N, de Oliveira CF, Brennan C; FLAMINGO study team. Once-daily dolutegravir versus darunavir plus ritonavir for treatment-naive adults with HIV-1 infection (FLAMINGO): 96 week results from a randomised, open-label, phase 3b study. Lancet HIV. 2015 Apr;2(4):e127-36. doi: 10.1016/S2352-3018(15)00027-2. Epub 2015 Mar 10.

Reference Type DERIVED
PMID: 26424673 (View on PubMed)

Clotet B, Feinberg J, van Lunzen J, Khuong-Josses MA, Antinori A, Dumitru I, Pokrovskiy V, Fehr J, Ortiz R, Saag M, Harris J, Brennan C, Fujiwara T, Min S; ING114915 Study Team. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet. 2014 Jun 28;383(9936):2222-31. doi: 10.1016/S0140-6736(14)60084-2. Epub 2014 Apr 1.

Reference Type DERIVED
PMID: 24698485 (View on PubMed)

Other Identifiers

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114915

Identifier Type: -

Identifier Source: org_study_id

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