ClinicalTrials.gov
ClinicalTrials.gov Menu

A Dose Ranging Trial of GSK1349572 and 2 NRTI in HIV-1 Infected, Therapy Naive Subjects (ING112276)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00951015
Recruitment Status : Completed
First Posted : August 3, 2009
Results First Posted : November 11, 2013
Last Update Posted : January 16, 2018
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus
Interventions: Drug: GSK1349572
Drug: efavirenz

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Randomization Phase participants received Dolutegravir (DTG 10, 25 or 50 milligrams[mg]) with Placebo/Efavirenz (EFV) for 96 Weeks . DTG participants who completed 96 Weeks continued or were switched to receive DTG 50 mg in Open label phase until DTG was locally available.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 278 par were screened of which 70 were screen failures and 208 were randomized; 205 received at least one dose of study medication and comprised the Intent-To-Treat exposed (ITT-E) population. 17 participants out of 155 from DTG arm withdrew during Randomization phase and total 138 participants were enrolled in an Open-label phase.

Reporting Groups
  Description
DTG 10 mg QD Participants received DTG 10 mg, DTG matching placebo, and Abacavir/lamivudine (ABC/3TC) 600 mg/300 mg or tenofovir/emtricitabine (TDF/FTC) 300 mg/200 mg orally once daily (QD) for 96 weeks.
DTG 25 mg QD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
DTG 50 mg QD Participants received DTG 50 mg matching placebo and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
EFV 600 mg QD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Open-label DTG 50 mg QD All DTG participants were switched to or continued DTG 50 mg with either ABC/3TC orally at 600 mg/300 mg (1 tablet) or TDF/FTC orally QD during the Open label phase

Participant Flow for 2 periods

Period 1:   Randomization Phase 96 Week
    DTG 10 mg QD   DTG 25 mg QD   DTG 50 mg QD   EFV 600 mg QD   Open-label DTG 50 mg QD
STARTED   53   51   51   50   0 
COMPLETED   48   44   46   40   0 
NOT COMPLETED   5   7   5   10   0 
Adverse Event                1                1                2                5                0 
Lack of Efficacy                1                1                0                0                0 
Protocol Violation                1                1                1                0                0 
Protocol-Defined Stopping Criteria                0                0                0                1                0 
Lost to Follow-up                0                3                1                2                0 
Withdrawal by Subject                2                1                1                2                0 

Period 2:   Open-label Phase
    DTG 10 mg QD   DTG 25 mg QD   DTG 50 mg QD   EFV 600 mg QD   Open-label DTG 50 mg QD
STARTED   0   0   0   0   138 
COMPLETED   0   0   0   0   88 
NOT COMPLETED   0   0   0   0   50 
Adverse Event                0                0                0                0                3 
Lack of Efficacy                0                0                0                0                1 
Protocol Violation                0                0                0                0                12 
Lost to Follow-up                0                0                0                0                12 
Withdrawal by Subject                0                0                0                0                14 
Physician Decision                0                0                0                0                8 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
DTG 10 mg QD Participants received Dolutegravir (DTG) 10 milligrams (mg), DTG matching placebo, and Abacavir (ABC)/Lamivudine (3TC) 600 mg/300 mg or Tenofovir (TDF)/Emtricitabine (FTC) 300 mg/200 mg orally once daily (QD) for 96 weeks.
DTG 25 mg QD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
DTG 50 mg QD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
EFV 600 mg QD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
Total Total of all reporting groups

Baseline Measures
   DTG 10 mg QD   DTG 25 mg QD   DTG 50 mg QD   EFV 600 mg QD   Total 
Overall Participants Analyzed 
[Units: Participants]
 53   51   51   50   205 
Age 
[Units: Years]
Mean (Standard Deviation)
 34.2  (9.25)   37.0  (9.79)   37.0  (8.89)   40.7  (11.19)   37.2  (10.00) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
         
Female      11  20.8%      5   9.8%      6  11.8%      6  12.0%      28  13.7% 
Male      42  79.2%      46  90.2%      45  88.2%      44  88.0%      177  86.3% 
Race/Ethnicity, Customized 
[Units: Participants]
         
African American/African Heritage (HER)   7   6   8   4   25 
American Indian or Alaska Native   1   3   4   2   10 
Japanese/East Asian HER/South East Asian HER   0   0   0   1   1 
Native Hawaiian or other Pacific Islander   3   0   0   0   3 
White   41   42   38   43   164 
African American/African HER & White   0   0   1   0   1 
Asian & White   1   0   0   0   1 


  Outcome Measures

1.  Primary:   Number of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 16   [ Time Frame: Week 16 ]

2.  Secondary:   Viral Change Over the Initial 2 Weeks of Treatment   [ Time Frame: Baseline and Week 2 ]

3.  Secondary:   Change From Baseline in HIV-1 RNA at the Indicated Time Points   [ Time Frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title Change From Baseline in HIV-1 RNA at the Indicated Time Points
Measure Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the value at Baseline.
Time Frame Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT-E Population. Only those participants available at the specified time points were analyzed (represented by n=X, X, X, X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT-E Population.

Reporting Groups
  Description
DTG 10 mg QD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
DTG 25 mg QD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
DTG 50 mg QD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.
EFV 600 mg QD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally QD for 96 weeks.

Measured Values
   DTG 10 mg QD   DTG 25 mg QD   DTG 50 mg QD   EFV 600 mg QD 
Participants Analyzed   53   51   51   50 
Change From Baseline in HIV-1 RNA at the Indicated Time Points 
[Units: Log10 c/mL]
Mean (Standard Deviation)
       
Week 1, n=53, 50, 48, 50         
Participants Analyzed   53   50   48   50 
Week 1, n=53, 50, 48, 50   -1.815  (0.3999)   -1.773  (0.4650)   -1.738  (0.3840)   -1.562  (0.4158) 
Week 2, n=53, 50, 50, 48         
Participants Analyzed   53   50   50   48 
Week 2, n=53, 50, 50, 48   -2.387  (0.4595)   -2.365  (0.5458)   -2.392  (0.4241)   -1.930  (0.4312) 
Week 4, n=53, 50, 50, 45         
Participants Analyzed   53   50   50   45 
Week 4, n=53, 50, 50, 45   -2.629  (0.5863)   -2.583  (0.6337)   -2.713  (0.5471)   -2.162  (0.5400) 
Week 8, n=52, 50, 49, 45         
Participants Analyzed   52   50   49   45 
Week 8, n=52, 50, 49, 45   -2.657  (0.6980)   -2.666  (0.6667)   -2.848  (0.6556)   -2.450  (0.5989) 
Week 12, n=53, 49, 49, 45         
Participants Analyzed   53   49   49   45 
Week 12, n=53, 49, 49, 45   -2.685  (0.6831)   -2.671  (0.6850)   -2.860  (0.6772)   -2.603  (0.5869) 
Week 16, n=52, 49, 49, 45         
Participants Analyzed   52   49   49   45 
Week 16, n=52, 49, 49, 45   -2.718  (0.6593)   -2.668  (0.6826)   -2.859  (0.6876)   -2.698  (0.6715) 
Week 20, n=52, 48, 49, 44         
Participants Analyzed   52   48   49   44 
Week 20, n=52, 48, 49, 44   -2.701  (0.6423)   -2.662  (0.6908)   -2.869  (0.6896)   -2.745  (0.6602) 
Week 24, n=52, 49, 48, 45         
Participants Analyzed   52   49   48   45 
Week 24, n=52, 49, 48, 45   -2.700  (0.6261)   -2.657  (0.6969)   -2.853  (0.6889)   -2.773  (0.7026) 
Week 32, n=52, 49, 47, 45         
Participants Analyzed   52   49   47   45 
Week 32, n=52, 49, 47, 45   -2.717  (0.6588)   -2.658  (0.6991)   -2.855  (0.6963)   -2.772  (0.7021) 
Week 40, n=51, 48, 47, 44         
Participants Analyzed   51   48   47   44 
Week 40, n=51, 48, 47, 44   -2.647  (0.7039)   -2.665  (0.7051)   -2.855  (0.6934)   -2.795  (0.7169) 
Week 48, n=51, 48, 48, 45         
Participants Analyzed   51   48   48   45 
Week 48, n=51, 48, 48, 45   -2.723  (0.6519)   -2.667  (0.6934)   -2.850  (0.6849)   -2.711  (0.7765) 
Week 60, n=50, 48, 48, 44         
Participants Analyzed   50   48   48   44 
Week 60, n=50, 48, 48, 44   -2.741  (0.6444)   -2.675  (0.7012)   -2.825  (0.7458)   -2.765  (0.7035) 
Week 72, n=51, 47, 48, 44         
Participants Analyzed   51   47   48   44 
Week 72, n=51, 47, 48, 44   -2.742  (0.6453)   -2.622  (0.8052)   -2.860  (0.6930)   -2.757  (0.7094) 
Week 84, n=51, 47, 47, 43         
Participants Analyzed   51   47   47   43 
Week 84, n=51, 47, 47, 43   -2.725  (0.6506)   -2.670  (0.7064)   -2.855  (0.6923)   -2.743  (0.7321) 
Week 96, n=48, 44, 46, 39         
Participants Analyzed   48   44   46   39 
Week 96, n=48, 44, 46, 39   -2.728  (0.6494)   -2.680  (0.7116)   -2.854  (0.7061)   -2.807  (0.7238) 

No statistical analysis provided for Change From Baseline in HIV-1 RNA at the Indicated Time Points



4.  Secondary:   Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at the Indicated Time Points   [ Time Frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 ]

5.  Secondary:   Number of Participants With New HIV-associated Conditions of the Indicated Class   [ Time Frame: From Baseline up to Week 96 ]

6.  Secondary:   Number of Participants With the Indicated Type of HIV-1 Disease Progression (AIDS or Death)   [ Time Frame: From Baseline up to Week 96 ]

7.  Secondary:   Number of Participants With Plasma HIV-1 RNA <50 c/mL   [ Time Frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 ]

8.  Secondary:   Number of Participants With Plasma HIV-1 RNA <400 c/mL   [ Time Frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 ]

9.  Secondary:   Number of Participants With Any Adverse Event (AE) and Any Serious Adverse Events (SAE)   [ Time Frame: From Baseline up to Week 96/Early Withdrawal ]

10.  Secondary:   Number of Participants With the Indicated Grade 1 to Grade 4 Treatment-emergent Clinical Chemistry and Hematology Toxicities   [ Time Frame: From Baseline up to Week 96/Early Withdrawal ]

11.  Secondary:   Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance   [ Time Frame: From Baseline up to Week 96/Early Withdrawal ]

12.  Secondary:   Number of Participants With the Indicated Treatment-emergent Major Mutations of Other Classes Detected at the Time of Protocol-defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance   [ Time Frame: From Baseline up to Week 96/Early Withdrawal ]

13.  Secondary:   Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) at the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance   [ Time Frame: From Baseline up to Week 96/Early Withdrawal ]

14.  Secondary:   Plasma DTG Concentration   [ Time Frame: Week 2, Week 12, and Week 24 ]

15.  Secondary:   AUC(0-tau) of DTG   [ Time Frame: Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2 ]

16.  Secondary:   Maximal Concentration (Cmax), Minimal Concentration (Cmin), and Concentration at the End of Dosing Interval (Ctau) of DTG   [ Time Frame: Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2 ]

17.  Secondary:   Pre-dose Concentration (C0) and C0 Avg of DTG   [ Time Frame: Week 2, Week 12, and Week 24 ]

18.  Secondary:   Time to Maximal Drug Concentration (Tmax) of DTG   [ Time Frame: Pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2 ]

19.  Secondary:   Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters   [ Time Frame: Week 2 ]

20.  Secondary:   Relationship Between the Change From Baseline in CD4+ Cell Counts at Week 96 and the Indicated Plasma DTG PK Parameters   [ Time Frame: Week 96 ]

21.  Secondary:   Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters   [ Time Frame: Week 96 ]

22.  Secondary:   Relationship Between Gastrointestinal System Organ Class AEs of Special Interest at Week 96 and the Indicated Plasma DTG PK Parameters   [ Time Frame: Week 96 ]

23.  Other Pre-specified:   Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at the Indicated Time Points   [ Time Frame: Baseline (Day 1), Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 32, Week 40, Week 48, Week 60, Week 72, Week 84, and Week 96 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information