Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01227824
Other study ID # 113086
Secondary ID
Status Completed
Phase Phase 3
First received
Last updated
Start date October 19, 2010
Est. completion date December 27, 2016

Study information

Verified date October 2018
Source ViiV Healthcare
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this trial is to assess the non-inferior antiviral activity of GSK1349572 50 mg once daily versus RAL 400mg twice daily over 48 weeks; non-inferiority will also be tested at Week 96. Both GSK1349572 and RAL will be given in combination with fixed-dose dual NRTI therapy (ABC/3TC or TDF/FTC). This study will be conducted in HIV-1 infected ART-naïve adult subjects.


Description:

ING113086 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:

1. GSK1349572 50 mg once daily (approximately 394 subjects) + fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC)

OR

2. 400 mg RAL twice daily (approximately 394 subjects) + fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC)

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 through the study until either it is locally available, as long as they continue to derive clinical benefit.

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


Recruitment information / eligibility

Status Completed
Enrollment 828
Est. completion date December 27, 2016
Est. primary completion date February 6, 2012
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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

Exclusion Criteria:

- Women who are pregnant or breastfeeding;

- Active Center for Disease and Prevention Control (CDC) Category C disease

- Moderate to severe hepatic impairment

- 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
GSK1349572 (dolutegravir)
GSK1349572 50 mg taken once daily with or without food
raltegravir
raltegravir 400mg taken twice daily
Other:
GSK1349572 Placebo
GSK1349572 placebo taken once daily
ABC/3TC
Abacavir/Lamivudine background therapy once daily
TDF/FTC
Tenofovir/emtricitabine background therapy once daily
raltegravir Placebo
raltegravir placebo taken twice daily

Locations

Country Name City State
Australia GSK Investigational Site Darlinghurst New South Wales
Australia GSK Investigational Site Melbourne Victoria
Australia GSK Investigational Site Surry Hills New South Wales
Canada GSK Investigational Site Hamilton Ontario
Canada GSK Investigational Site Montreal Quebec
Canada GSK Investigational Site Montreal Quebec
Canada GSK Investigational Site Ottawa Ontario
Canada GSK Investigational Site Toronto Ontario
Canada GSK Investigational Site Toronto Ontario
Canada GSK Investigational Site Vancouver British Columbia
France GSK Investigational Site Garches
France GSK Investigational Site Le Kremlin Bicêtre cedex
France GSK Investigational Site Levallois Perret
France GSK Investigational Site Lyon Cedex 03
France GSK Investigational Site Marseille
France GSK Investigational Site Nantes
France GSK Investigational Site Paris
France GSK Investigational Site Paris Cedex 10
France GSK Investigational Site Paris Cedex 12
France GSK Investigational Site Paris Cedex 13
France GSK Investigational Site Paris Cedex 4
Germany GSK Investigational Site Berlin
Germany GSK Investigational Site Bonn Nordrhein-Westfalen
Germany GSK Investigational Site Dortmund Nordrhein-Westfalen
Germany GSK Investigational Site Frankfurt Hessen
Germany GSK Investigational Site Fuerth Bayern
Germany GSK Investigational Site Hamburg
Germany GSK Investigational Site Hamburg
Germany GSK Investigational Site Hannover Niedersachsen
Germany GSK Investigational Site Koeln Nordrhein-Westfalen
Germany GSK Investigational Site Muenchen Bayern
Italy GSK Investigational Site Brescia Lombardia
Italy GSK Investigational Site Cona (Ferrara) Emilia-Romagna
Italy GSK Investigational Site Genova Liguria
Italy GSK Investigational Site Roma Lazio
Italy GSK Investigational Site Rovigo Veneto
Italy GSK Investigational Site Torino Piemonte
Russian Federation GSK Investigational Site Krasnodar
Russian Federation GSK Investigational Site Lipetsk
Russian Federation GSK Investigational Site Moscow
Russian Federation GSK Investigational Site N.Novgorod
Russian Federation GSK Investigational Site Orel
Russian Federation GSK Investigational Site Perm
Russian Federation GSK Investigational Site Saratov
Russian Federation GSK Investigational Site Smolensk
Russian Federation GSK Investigational Site St. Petersburg
Russian Federation GSK Investigational Site St. Petersburg
Russian Federation GSK Investigational Site Volgograd
Spain GSK Investigational Site (Móstoles) Madrid
Spain GSK Investigational Site Alcala de Henares
Spain GSK Investigational Site Alicante
Spain GSK Investigational Site Almería
Spain GSK Investigational Site Badalona
Spain GSK Investigational Site Barcelona
Spain GSK Investigational Site Barcelona
Spain GSK Investigational Site Barcelona
Spain GSK Investigational Site Barcelona
Spain GSK Investigational Site Cartagena (Murcia)
Spain GSK Investigational Site Córdoba
Spain GSK Investigational Site Granada
Spain GSK Investigational Site Granada
Spain GSK Investigational Site La Coruña
Spain GSK Investigational Site La Laguna (Santa Cruz De Tenerife)
Spain GSK Investigational Site Madrid
Spain GSK Investigational Site Madrid
Spain GSK Investigational Site Madrid
Spain GSK Investigational Site Madrid
Spain GSK Investigational Site Madrid
Spain GSK Investigational Site Madrid
Spain GSK Investigational Site Malaga
Spain GSK Investigational Site Mataró
Spain GSK Investigational Site Murcia
Spain GSK Investigational Site San Sebastián
Spain GSK Investigational Site Sevilla
Spain GSK Investigational Site Valencia
Spain GSK Investigational Site Vigo ( Pontevedra)
United Kingdom GSK Investigational Site Birmingham Warwickshire
United Kingdom GSK Investigational Site Brighton
United Kingdom GSK Investigational Site Crumpsall, Manchester
United Kingdom GSK Investigational Site London
United Kingdom GSK Investigational Site London
United States GSK Investigational Site Atlanta Georgia
United States GSK Investigational Site Austin Texas
United States GSK Investigational Site Charlotte North Carolina
United States GSK Investigational Site Columbia South Carolina
United States GSK Investigational Site Dallas Texas
United States GSK Investigational Site Denver Colorado
United States GSK Investigational Site Fort Lauderdale Florida
United States GSK Investigational Site Fort Pierce Florida
United States GSK Investigational Site Hillsborough New Jersey
United States GSK Investigational Site Houston Texas
United States GSK Investigational Site Houston Texas
United States GSK Investigational Site Little Rock Arkansas
United States GSK Investigational Site Long Beach California
United States GSK Investigational Site Los Angeles California
United States GSK Investigational Site Los Angeles California
United States GSK Investigational Site Phoenix Arizona
United States GSK Investigational Site Saint Louis Missouri
United States GSK Investigational Site Seattle Washington
United States GSK Investigational Site Torrance California
United States GSK Investigational Site Washington District of Columbia

Sponsors (3)

Lead Sponsor Collaborator
ViiV Healthcare GlaxoSmithKline, Shionogi

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Germany,  Italy,  Russian Federation,  Spain,  United Kingdom, 

References & Publications (2)

Brinson C, Walmsley S, Arasteh K, et al. Dolutegravir treatment response and safety by key subgroups in treatment naive HIV-infected individuals. Published at: Conference on Retroviruses and Opportunistic Infections - 20th Annual; March 3-6, 2013; Atlanta, GA.

Raffi F, Rachlis A, Stellbrink HJ, Hardy WD, Torti C, Orkin C, Bloch M, Podzamczer D, Pokrovsky V, Pulido F, Almond S, Margolis D, Brennan C, Min S; SPRING-2 Study Group. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet. 2013 Mar 2;381(9868):735-43. doi: 10.1016/S0140-6736(12)61853-4. Epub 2013 Jan 8. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48 Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) with <50 c/mL was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) snapshot algorithm. The algorithm treats all participants without HIV-1 RNA data as non-responders, as well as participants who switch their concomitant Antiretroviral Therapy (ART) prior to Week 48 as follows: background ART substitutions not permitted per study; background ART substitutions permitted per study 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 will be determined by the last available HIV-1 RNA assessment while the subject was on-treatment. Intent-to-Treat Exposed (ITT-E) Population comprised all randomized participants who received at least one dose of study medication. Baseline up to Week 48
Secondary Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance. Number of participants with detectable virus that has genotypic or phenotypic evidence of Integrase Inhibitor (INI) resistance were assessed at Week 48 and Week 96. Integrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the deoxyribonucleic acid (DNA) of the host cell. Week 48 and Week 96
Secondary Number of Participants With Plasma HIV-1 RNA <50 c/mL The number of participants with plasma HIV-1 RNA level <50 c/mL was assessed at Week 96. Week 96
Secondary Number of Participants With Plasma HIV-1 RNA <400 c/mL The number of participants with plasma HIV-1 RNA level <400 c/mL was assessed at Week 48 and Week 96. Week 48 and Week 96
Secondary Change From Baseline in Plasma HIV-1 RNA Over Time Change from Baseline in plasma HIV-1 RNA over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Baseline was defined as the measurements performed on Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles). Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary Absolute Values in Plasma HIV-1 RNA Over Time Absolute values in plasma HIV-1 RNA over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles). Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immuno compromise. The CD4 count is used to stage the participants disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start ART. Changes from Baseline in CD4+ cell counts over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Baseline was defined as measurements performed on Day 1. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles). Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary Absolute Values in CD4+ Cell Counts Over Time CD4 lymphocyte cells (also called T-cells or T-helper cells) are the primary targets of HIV. The CD4 count and the CD4 percentage mark the degree of immuno compromise. The CD4 count is used to stage the patient's disease, determine the risk of opportunistic illnesses, assess prognosis, and guide decisions about when to start antiretroviral therapy absolute values in CD4+ cell counts over time was assessed at Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96. Only those participants with data available at the specified time points were analyzed (represented by n=x,x in the category titles). Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences Clinical disease progression (CDP) was assessed according to the Centers for Disease Control and Prevention (CDC) HIV-1 classification system. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition. Indicators of CDP were defined as: CDC CAT A at Baseline to a CDC CAT C event (EV); CDC CAT B at Baseline to a CDC CAT C EV; CDC CAT C at Baseline to a new CDC CAT C EV; or CDC CAT A, B, or C at Baseline to death. From Baseline until Week 96
Secondary Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs) All Grade 1 to 4 post-Baseline-emergent chemistry toxicities included alanine aminotransferase (ALT), alkaline phosphatase (ALP), asparate aminotransferase (AST), carbon dioxide (CO2) content/bicarbonate, cholesterol, creatine kinase (CK), creatinine, hyperglycemia, hyperkalemia, hypernatremia, hypoglycemia, hypokalemia, hyponatremia, low density lipoprotein (LDL) cholesterol calculation, lipase, phosphorus inorganic, total bilirubin, and triglycerides. All Grade 1 to 4 post-Baseline-emergent hematology toxities included hemoglobin, platelet count, total neutrophils, and white blood cell count. The Division of AIDS (DAIDS) defined toxicity grades as follows: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, potentially life threatening; Grade 5, death. Safety Population: all participants who received at least one dose of investigational product From Baseline until Week 96
Secondary Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau [AUC(0-tau)] of DTG AUC is defined as the area under the DTG concentration-time curve as a measure of drug exposure over time. AUC(0-tau) is defined as the area under the plasma concentration-time curve from time zero to time tau over a dosing interval at steady state, where tau is the length of the dosing interval of DTG. The predicted individual AUC(0-tau) were obtained from the final population PK model by an empirical Bayes estimation. Blood samples for PK assessments were collected at pre-dose (within 15 minutes prior to dose) at Week 4, Week 24, and Week 48 and 1 to 3 hours post-dose or 4 to 12 hours post-dose at Week 4 and Week 24. If 1 to 3 hours post-dose was completed at Week 4, then the 4 to12 hour post-dose must be obtained at Week 48, and vice versa. The Pharmacokinetic (PK) Concentration Population comprised of all participants who received DTG, had undergone PK sampling during the study, and provided evaluable DTG plasma concentration data. Week 4, Week 24, and Week 48
Secondary Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG The maximum plasma concentration (Cmax) and concentration at the end of a dosing interval (Ctau) of DTG were assessed at Week 48. The predicted individual Cmax and Ctau were obtained from the final population PK model by simulation of the concentration-time profiles. Blood samples for PK assessments were collected at pre-dose (within 15 minutes prior to dose) at Week 4, Week 24, and Week 48 and 1 to 3 hours post-dose or 4 to 12 hours post-dose at Week 4 and Week 24. If 1 to 3 hour post-dose was completed at Week 4, then the 4 to12 hour post-dose must be obtained at Week 48, and vice versa. Week 4, Week 24, and Week 48
See also
  Status Clinical Trial Phase
Completed NCT03327740 - PRJ2203: Dolutegravir Post Authorization Safety Study (PASS)
Completed NCT00257621 - GW640385 Plus Ritonavir And NRTIs For 48 Weeks In HIV-1 Infected Adults Phase 2
Completed NCT01597648 - A Study to Evaluate the Bioequivalence of a Combined Formulated Tablet Compared With Maraviroc and Combivir™ Phase 1
Completed NCT01205243 - ZIAGEN® Post-marketing Surveillance
Withdrawn NCT01283100 - A Drug Interaction Study Evaluating Plasma GSK2248761 and GSK1349572 Pharmacokinetics in Healthy Adult Subjects. Phase 1
Completed NCT00440947 - Induction/Simplification With Atazanavir + Ritonavir + Abacavir/Lamivudine Fixed-Dose Combination In HIV-1 Infection Phase 3
Completed NCT00450580 - HIV-1 Infection Study of Once a Day Versus Twice a Day Protease Inhibitor in Antiretroviral Treatment Naive Adults Phase 3
Completed NCT00481390 - Prospective Epidemiological Study Of The Prevalence Of HLA-B*5701 In HIV-1 Infected Patients N/A
Completed NCT00549198 - KIVEXA Vs TRUVADA, Both Administered With Efavirenz, In ART-Naive Subjects Phase 4
Completed NCT00242840 - Observational Study Of A Protease Inhibitor (PI) Containing Regimen In Subjects With PI Mutations Selected During Prior Treatment With GW433908 (Fosamprenavir) Phase 3
Terminated NCT00197145 - Study Of Chemokine Coreceptor 5 (CCR5) Antagonist GW873140 In R5-Tropic Treatment-Experienced HIV-Infected Subjects Phase 3
Completed NCT00089583 - 48-Week Study Of GW433908 And Ritonavir Or GW433908 Alone, Twice Daily In Pediatric Patients With HIV Infection Phase 2
Completed NCT00044577 - New Tablet Containing Two FDA Approved Anti-HIV Drugs For Antiretroviral Therapy Experienced HIV-1 Infected Subjects Phase 3
Terminated NCT00104429 - GW873140 In Combination With Combivir In HIV Infected Subjects Phase 2
Completed NCT01263015 - A Trial Comparing GSK1349572 50mg Plus Abacavir/Lamivudine Once Daily to Atripla (Also Called The SINGLE Trial) Phase 3
Terminated NCT00102778 - GW873140 In Combination With Kaletra In HIV Infected Subjects Phase 2
Completed NCT00094523 - Fosamprenavir Versus Other Protease Inhibitors Phase 3
Completed NCT00046176 - A HIV Study Of A Fixed-Dose Combination Tablet In Antiretroviral Experienced Patients Phase 3
Terminated NCT00242879 - A Dose Ranging Study Of GW640385 Boosted With Ritonavir (Rtv) In Comparison To A RTV-Boosted Protease Inhibitor (PI) In HIV-1 Infected PI-Experienced Adults Phase 2
Completed NCT00082394 - A Study Comparing The Safety, Tolerability and Efficacy of Trizivir VS Combivir & Atazanavir In Subjects With HIV Phase 4