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

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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 ]

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

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: ViiV Healthcare
phone: 866-435-7343


Publications:

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT00951015     History of Changes
Other Study ID Numbers: 112276
First Submitted: July 30, 2009
First Posted: August 3, 2009
Results First Submitted: August 22, 2013
Results First Posted: November 11, 2013
Last Update Posted: January 16, 2018