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

NCT01449929 | Completed Phase 3 Results FDA Drug

• 1 other identifier: 114915
• Study Type: interventional
• Target: 488
• Locations: 9 countries
• Sites: 66

Brief Summary

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.

Conditions

Infection, Human Immunodeficiency Virus

Keywords

ritonavir; HIV; HAART; darunavir; antiretroviral; dolutegravir; GSK1349572

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 48

  Assessment was done using Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) "snapshot" algorithm.This algorithm treated all participants without HIV-1 RNA data at Week 48 as nonresponders, as well as participants who switched their concomitant ART prior to Week 48 as follows: background ART substitutions non-permitted per protocol (one background ART substitution was permitted for safety or tolerability); background ART substitutions permitted per protocol unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure was determined by the last available HIV-1 RNA assessment while the participant was on-treatment in the snapshot window (Week 48 +/- 6 weeks). Modified Intent-To-Treat Exposed (mITT-E) Population:all randomized participants who received at least one dose of investigational product

  Week 48

Secondary Outcomes (15)

• Time to Virologic Suppression (<50 Copies/mL) Through Week 48

  From Baseline through Week 48

• Percentage of Participants With Plasma HIV-1 RNA <400 c/mL at Week 48

  Week 48

• Change From Baseline in Plasma HIV-1 RNA (log10 c/mL) at Weeks 4, 8, 12, 16, 24, 36 and 48

  Baseline, Weeks 4, 8, 12, 16, 24, 36 and 48

• Change From Baseline in CD4+ and CD8+ Cell Counts

  Baseline and Weeks 4, 8, 12, 16, 36 and 48 for CD4+ and Baseline and Weeks 4, 12, 24 and 48 for CD8+

• Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shift to CDC Class C, or New CDC Class C or Death at Week 48

  Week 48

Study Arms (2)

dolutegravir 50mg once daily (OAD)

EXPERIMENTAL

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

Drug: dolutegravir 50 mg OAD

darunavir 800mg OAD in combination with ritonavir 100mg OAD

ACTIVE COMPARATOR

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

Drug: darunavir 800mg OAD; Drug: ritonavir 100mg OAD

Interventions

dolutegravir 50 mg OAD DRUG

1 x 50 mg tablet OAD

dolutegravir 50mg once daily (OAD)

darunavir 800mg OAD DRUG

2 x 400mg tablets OAD

darunavir 800mg OAD in combination with ritonavir 100mg OAD

ritonavir 100mg OAD DRUG

1 x 100mg tablet OAD

darunavir 800mg OAD in combination with ritonavir 100mg OAD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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
• 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• GlaxoSmithKline: collaborator

Study Sites (66)

GSK Investigational Site

Birmingham, Alabama, 35294, United States

Location

GSK Investigational Site

Los Angeles, California, 90027, United States

Location

GSK Investigational Site

Los Angeles, California, 90069, United States

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GSK Investigational Site

Aurora, Colorado, 80045, United States

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GSK Investigational Site

Denver, Colorado, 80209, United States

Location

GSK Investigational Site

Norwalk, Connecticut, 06851, United States

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GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20009, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20037, United States

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GSK Investigational Site

Daytona Beach, Florida, 32117, United States

Location

GSK Investigational Site

Orlando, Florida, 32803, United States

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GSK Investigational Site

Tampa, Florida, 33614, United States

Location

GSK Investigational Site

Vero Beach, Florida, 32690, United States

Location

GSK Investigational Site

Augusta, Georgia, 30912, United States

Location

GSK Investigational Site

Decatur, Georgia, 30033, United States

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GSK Investigational Site

Macon, Georgia, 31201, United States

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GSK Investigational Site

Savannah, Georgia, 31401, United States

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GSK Investigational Site

Springfield, Massachusetts, 01105, United States

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GSK Investigational Site

Detroit, Michigan, 48202, United States

Location

GSK Investigational Site

Minneapolis, Minnesota, 55415, United States

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GSK Investigational Site

Kansas City, Missouri, 64111, United States

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GSK Investigational Site

Chapel Hill, North Carolina, 27514, United States

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GSK Investigational Site

Charlotte, North Carolina, 28209, United States

Location

GSK Investigational Site

Winston-Salem, North Carolina, 27157-1042, United States

Location

GSK Investigational Site

Cincinnati, Ohio, 45267, United States

Location

GSK Investigational Site

Portland, Oregon, 97210, United States

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GSK Investigational Site

Philadelphia, Pennsylvania, 19104, United States

Location

GSK Investigational Site

Providence, Rhode Island, 02906, United States

Location

GSK Investigational Site

Dallas, Texas, 75204, United States

Location

GSK Investigational Site

Dallas, Texas, 75219, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

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GSK Investigational Site

Longview, Texas, 75605, United States

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GSK Investigational Site

Seattle, Washington, 98104, United States

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GSK Investigational Site

Montpellier, 34295, France

Location

GSK Investigational Site

Nantes, 44093, France

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GSK Investigational Site

Paris, 75018, France

Location

GSK Investigational Site

Paris, 75475, France

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GSK Investigational Site

Paris, 75970, France

Location

GSK Investigational Site

Saint-Denis, 93205, France

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GSK Investigational Site

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

GSK Investigational Site

Frankfurt am Main, Hesse, 60590, Germany

Location

GSK Investigational Site

Hamburg, 20246, Germany

Location

GSK Investigational Site

Modena, Emilia-Romagna, 41150, Italy

Location

GSK Investigational Site

Rome, Lazio, 00149, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20127, Italy

Location

GSK Investigational Site

Milan, Lombardy, 20142, Italy

Location

GSK Investigational Site

Turin, Piedmont, 10149, Italy

Location

GSK Investigational Site

Ponce, 00717, Puerto Rico

Location

GSK Investigational Site

San Juan, 00909, Puerto Rico

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GSK Investigational Site

San Juan, Puerto Rico

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GSK Investigational Site

Bucharest, 021105, Romania

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GSK Investigational Site

Bucharest, 030303, Romania

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GSK Investigational Site

Constanța, 900708, Romania

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GSK Investigational Site

Krasnodar, 350015, Russia

Location

GSK Investigational Site

Moscow, 105275, Russia

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GSK Investigational Site

Saint Petersburg, 196645, Russia

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GSK Investigational Site

Saratov, 410009, Russia

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GSK Investigational Site

Volgograd, 400040, Russia

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GSK Investigational Site

Badalona, 08916, Spain

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Barcelona, 08907, Spain

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GSK Investigational Site

Madrid, 28041, Spain

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GSK Investigational Site

Seville, 41013, Spain

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GSK Investigational Site

Bern, 3010, Switzerland

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GSK Investigational Site

Lausanne, 1011, Switzerland

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GSK Investigational Site

Zurich, CH-8091, Switzerland

Location

Related Publications (2)

• 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.

  PMID: 26424673 DERIVED

• 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.

  PMID: 24698485 DERIVED

MeSH Terms

Conditions

Infections; Acquired Immunodeficiency Syndrome

Interventions

dolutegravir; Darunavir; Ritonavir

Condition Hierarchy (Ancestors)

HIV Infections; 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)

Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2011
• First Posted: October 10, 2011
• Study Start: October 31, 2011
• Primary Completion: April 22, 2013
• Study Completion: December 26, 2016
• Last Updated: January 16, 2018
• Results First Posted: March 27, 2014

Record last verified: 2017-10

Locations

RO (3); IT (5); PR (3); DE (3); FR (6); RU (5); ES (5); US (33); CH (3)