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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00951015
First received: July 30, 2009
Last updated: December 19, 2013
Last verified: October 2013
Results First Received: August 22, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus
Interventions: Drug: GSK1349572
Drug: efavirenz

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible participants (par.) were randomized (ran) to receive Dolutegravir (DTG) (3 dose groups) or Efavirenz for 96 weeks. At Week 96, par. ran. to any dose of DTG entered an open-label phase and continued to receive DTG at the selected dose of 50 milligrams. A total of 208 par. were ran., and 205 received at least one dose of study medication.

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

Participant Flow:   Overall Study
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD  
STARTED     53     51     51     50  
Ongoing     47     45     46     8  
COMPLETED     0     0     0     32  
NOT COMPLETED     53     51     51     18  
Adverse Event                 1                 1                 2                 5  
Lack of Efficacy                 1                 1                 0                 0  
Protocol Violation                 1                 1                 1                 0  
Protocol-Defined Stopping Criteria                 0                 0                 0                 1  
Lost to Follow-up                 0                 2                 1                 2  
Withdrawal by Subject                 3                 1                 1                 2  
Ongoing                 47                 45                 46                 8  



  Baseline Characteristics
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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 OD 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 (OD) for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.
Total Total of all reporting groups

Baseline Measures
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD     Total  
Number of Participants  
[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  
Gender  
[units: Participants]
         
Female     11     5     6     6     28  
Male     42     46     45     44     177  
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
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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:   Cmax, Cmin, and Ctau of DTG   [ Time Frame: pre-dose and 2, 3, 4, 8, and 24 hours post-dose at Week 2 ]

17.  Secondary:   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 ]
  Hide Outcome Measure 19

Measure Type Secondary
Measure Title Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters
Measure Description Relationships between Week 2 plasma DTG PK parameters (AUC[0-tau] [area under the time concentration curve over the dosing interval], Cmax [maximal concentration], and Ctau [concentration at the end of the dosing interval]) and the change from Baseline in plasma HIV-1 RNA at Week 2 (calculated as the post-Baseline value minus the value at Baseline) was assessed using Pearson’s correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between plasma HIV-1 RNA and plasma DTG PK parameters and ranges from -1 to 1. A value of 0 indicates no statistical association; a value close to -1 or 1 indicates a higher association. Because PK was assessed for DTG, no participants in the EFV treatment group were analyzed.
Time Frame Week 2  
Safety Issue No  

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.
PK/Pharmacodynamic (PD) Analysis Population: all participants with available PD measures (e.g., safety and/or efficacy data) and with evaluable DTG plasma concentration data considered suitable for investigation of relationship with the PD measures. Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
DTG 10 mg OD Participants received DTG 10 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 25 mg OD Participants received DTG 25 mg, DTG matching placebo, and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
DTG 50 mg OD Participants received DTG 50 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks. Following Week 96, participants continued to receive DTG 50 mg OD.
EFV 600 mg OD Participants received Efavirenz (EFV) 600 mg and ABC/3TC 600 mg/300 mg or TDF/FTC 300 mg/200 mg orally OD for 96 weeks.
Overall DTG All participants who received DTG in any DTG treatment group (DTG 10 mg OD, DTG 25 mg OD, and DTG 50 mg OD)

Measured Values
    DTG 10 mg OD     DTG 25 mg OD     DTG 50 mg OD     EFV 600 mg OD     Overall DTG  
Number of Participants Analyzed  
[units: participants]
  15     15     15     0     45  
Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters  
[units: Pearson's correlation coefficient]
         
AUC(0-tau)     0.426     -0.018     -0.258         -0.086  
Cmax     0.452     -0.051     -0.150         -0.055  
Ctau     0.273     -0.100     -0.263         -0.129  

No statistical analysis provided for Relationship Between the Change From Baseline in Plasma HIV-1 RNA at Week 2 and the Indicated Plasma DTG PK Parameters



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
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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
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