Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01227824




Registration number
NCT01227824
Ethics application status
Date submitted
14/10/2010
Date registered
25/10/2010
Date last updated
9/10/2018

Titles & IDs
Public title
A Trial Comparing GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily
Scientific title
A Randomized, Double Blind Study of the Safety and Efficacy of GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily Both Administered With Fixed-dose Dual Nucleoside Reverse Transcriptase Inhibitor Therapy Over 96 Weeks in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects
Secondary ID [1] 0 0
113086
Universal Trial Number (UTN)
Trial acronym
SPRING-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infection, Human Immunodeficiency Virus I 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK1349572 (dolutegravir)
Treatment: Drugs - raltegravir
Other interventions - GSK1349572 Placebo
Other interventions - ABC/3TC
Other interventions - TDF/FTC
Other interventions - raltegravir Placebo

Experimental: GSK1349572 (N=~394) - GSK1349572 50mg once daily + raltegravir placebo twice daily + NRTI background therapy once daily

Active comparator: raltegravir (N=~394) - raltegravir 400mg twice daily + GSK1349572 placebo once daily + NRTI background therapy once daily


Treatment: Drugs: GSK1349572 (dolutegravir)
GSK1349572 50 mg taken once daily with or without food

Treatment: Drugs: raltegravir
raltegravir 400mg taken twice daily

Other interventions: GSK1349572 Placebo
GSK1349572 placebo taken once daily

Other interventions: ABC/3TC
Abacavir/Lamivudine background therapy once daily

Other interventions: TDF/FTC
Tenofovir/emtricitabine background therapy once daily

Other interventions: raltegravir Placebo
raltegravir placebo taken twice daily
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline up to Week 48
Secondary outcome [1] 0 0
Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance.
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Week 48 and Week 96
Secondary outcome [2] 0 0
Number of Participants With Plasma HIV-1 RNA <50 c/mL
Assessment method [2] 0 0
The number of participants with plasma HIV-1 RNA level \<50 c/mL was assessed at Week 96.
Timepoint [2] 0 0
Week 96
Secondary outcome [3] 0 0
Number of Participants With Plasma HIV-1 RNA <400 c/mL
Assessment method [3] 0 0
The number of participants with plasma HIV-1 RNA level \<400 c/mL was assessed at Week 48 and Week 96.
Timepoint [3] 0 0
Week 48 and Week 96
Secondary outcome [4] 0 0
Change From Baseline in Plasma HIV-1 RNA Over Time
Assessment method [4] 0 0
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).
Timepoint [4] 0 0
Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary outcome [5] 0 0
Absolute Values in Plasma HIV-1 RNA Over Time
Assessment method [5] 0 0
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).
Timepoint [5] 0 0
Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary outcome [6] 0 0
Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time
Assessment method [6] 0 0
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).
Timepoint [6] 0 0
Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary outcome [7] 0 0
Absolute Values in CD4+ Cell Counts Over Time
Assessment method [7] 0 0
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).
Timepoint [7] 0 0
Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96
Secondary outcome [8] 0 0
Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences
Assessment method [8] 0 0
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.
Timepoint [8] 0 0
From Baseline until Week 96
Secondary outcome [9] 0 0
Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs)
Assessment method [9] 0 0
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
Timepoint [9] 0 0
From Baseline until Week 96
Secondary outcome [10] 0 0
Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau [AUC(0-tau)] of DTG
Assessment method [10] 0 0
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.
Timepoint [10] 0 0
Week 4, Week 24, and Week 48
Secondary outcome [11] 0 0
Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG
Assessment method [11] 0 0
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.
Timepoint [11] 0 0
Week 4, Week 24, and Week 48

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/10/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
27/12/2016
Sample size
Target
Accrual to date
Final
828
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
GSK Investigational Site - Darlinghurst
Recruitment hospital [2] 0 0
GSK Investigational Site - Surry Hills
Recruitment hospital [3] 0 0
GSK Investigational Site - Melbourne
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2010 - Surry Hills
Recruitment postcode(s) [3] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Missouri
Country [9] 0 0
United States of America
State/province [9] 0 0
New Jersey
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
South Carolina
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
British Columbia
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario
Country [16] 0 0
Canada
State/province [16] 0 0
Quebec
Country [17] 0 0
France
State/province [17] 0 0
Garches
Country [18] 0 0
France
State/province [18] 0 0
Le Kremlin Bicêtre cedex
Country [19] 0 0
France
State/province [19] 0 0
Levallois Perret
Country [20] 0 0
France
State/province [20] 0 0
Lyon Cedex 03
Country [21] 0 0
France
State/province [21] 0 0
Marseille
Country [22] 0 0
France
State/province [22] 0 0
Nantes
Country [23] 0 0
France
State/province [23] 0 0
Paris Cedex 10
Country [24] 0 0
France
State/province [24] 0 0
Paris Cedex 12
Country [25] 0 0
France
State/province [25] 0 0
Paris Cedex 13
Country [26] 0 0
France
State/province [26] 0 0
Paris Cedex 4
Country [27] 0 0
France
State/province [27] 0 0
Paris
Country [28] 0 0
Germany
State/province [28] 0 0
Bayern
Country [29] 0 0
Germany
State/province [29] 0 0
Hessen
Country [30] 0 0
Germany
State/province [30] 0 0
Niedersachsen
Country [31] 0 0
Germany
State/province [31] 0 0
Nordrhein-Westfalen
Country [32] 0 0
Germany
State/province [32] 0 0
Berlin
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Italy
State/province [34] 0 0
Emilia-Romagna
Country [35] 0 0
Italy
State/province [35] 0 0
Lazio
Country [36] 0 0
Italy
State/province [36] 0 0
Liguria
Country [37] 0 0
Italy
State/province [37] 0 0
Lombardia
Country [38] 0 0
Italy
State/province [38] 0 0
Piemonte
Country [39] 0 0
Italy
State/province [39] 0 0
Veneto
Country [40] 0 0
Russian Federation
State/province [40] 0 0
Krasnodar
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Lipetsk
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Moscow
Country [43] 0 0
Russian Federation
State/province [43] 0 0
N.Novgorod
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Orel
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Perm
Country [46] 0 0
Russian Federation
State/province [46] 0 0
Saratov
Country [47] 0 0
Russian Federation
State/province [47] 0 0
Smolensk
Country [48] 0 0
Russian Federation
State/province [48] 0 0
St. Petersburg
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Volgograd
Country [50] 0 0
Spain
State/province [50] 0 0
(Móstoles) Madrid
Country [51] 0 0
Spain
State/province [51] 0 0
Alcala de Henares
Country [52] 0 0
Spain
State/province [52] 0 0
Alicante
Country [53] 0 0
Spain
State/province [53] 0 0
Almería
Country [54] 0 0
Spain
State/province [54] 0 0
Badalona
Country [55] 0 0
Spain
State/province [55] 0 0
Barcelona
Country [56] 0 0
Spain
State/province [56] 0 0
Cartagena (Murcia)
Country [57] 0 0
Spain
State/province [57] 0 0
Córdoba
Country [58] 0 0
Spain
State/province [58] 0 0
Granada
Country [59] 0 0
Spain
State/province [59] 0 0
La Coruña
Country [60] 0 0
Spain
State/province [60] 0 0
La Laguna (Santa Cruz De Tenerife)
Country [61] 0 0
Spain
State/province [61] 0 0
Madrid
Country [62] 0 0
Spain
State/province [62] 0 0
Malaga
Country [63] 0 0
Spain
State/province [63] 0 0
Mataró
Country [64] 0 0
Spain
State/province [64] 0 0
Murcia
Country [65] 0 0
Spain
State/province [65] 0 0
San Sebastián
Country [66] 0 0
Spain
State/province [66] 0 0
Sevilla
Country [67] 0 0
Spain
State/province [67] 0 0
Valencia
Country [68] 0 0
Spain
State/province [68] 0 0
Vigo ( Pontevedra)
Country [69] 0 0
United Kingdom
State/province [69] 0 0
Warwickshire
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Brighton
Country [71] 0 0
United Kingdom
State/province [71] 0 0
Crumpsall, Manchester
Country [72] 0 0
United Kingdom
State/province [72] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
ViiV Healthcare
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Shionogi
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/industry
Name [2] 0 0
GlaxoSmithKline
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
ViiV Healthcare
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01227824