Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified October 2013 by ViiV Healthcare.
Recruitment status was:  Active, not recruiting
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
  Hide Participant Flow

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
  Hide 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 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 
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) 
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
  Show All 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:   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 ]

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 ]
  Hide Outcome Measure 21

Measure Type Secondary
Measure Title Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters
Measure Description Relationships between log-transformed plasma DTG PK parameters (AUC[0-tau], Cmax, C0, C0avg, Ctau, and Cmin) and safety parameters (AE occurrence, maximum AE intensity, alanine aminotransferase [ALT], change from Baseline [CFB] in ALT, total bilirubin, CFB in total bilirubin, creatine kinase, CFB in creatine kinase, triglycerides, CFB in triglycerides, lipase, CFB in lipase, total cholesterol [TC], CFB in TC) was assessed using Pearson’s correlation analyses. The Pearson's correlation coefficient is a measure of the correlation between safety parameters 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. The presence of >=1 AE was used for AE occurrence. The most severe AE grade/intensity was used for maximum AE intensity. Maximum laboratory values per participant were used for safety parameters. CFB was calculated as the post-Baseline value minus the value at Baseline.
Time Frame Week 96  
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/PD Analysis Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the PK/PD Analysis Population.

Reporting Groups
  Description
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
   Overall DTG 
Participants Analyzed 
[Units: Participants]
 142 
Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters 
[Units: Pearson's correlation coefficient]
 
AUC(0-tau) versus AE occurrence, n=45   0.114 
AUC(0-tau) versus maximum AE intensity, n=45   0.171 
AUC(0-tau) versus ALT, n=45   -0.196 
AUC(0-tau) versus CFB in ALT, n=45   -0.201 
AUC(0-tau) versus total bilirubin, n=45   0.364 
AUC(0-tau) versus CFB in total bilirubin, n=45   0.147 
AUC(0-tau) versus creatine kinase, n=45   -0.168 
AUC(0-tau) versus CFB in creatine kinase, n=45   -0.145 
AUC(0-tau) vs Triglycerides, n=45   0.104 
AUC(0-tau) versus CFB in triglycerides, n=45   0.216 
AUC(0-tau) versus lipase, n=45   -0.066 
AUC(0-tau) versus CFB in lipase, n=45   0.092 
AUC(0-tau) versus total cholesterol, n=45   -0.097 
AUC(0-tau) versus CFB in total cholesterol, n=45   -0.153 
Cmax versus AE occurrence, n=45   0.061 
Cmax versus maximum AE intensity, n=45   0.110 
Cmax versus ALT, n=45   -0.135 
Cmax versus CFB in ALT, n=45   -0.135 
Cmax versus total bilirubin, n=45   0.265 
Cmax versus CFB in total bilirubin, n=45   0.033 
Cmax versus creatine kinase, n=45   -0.188 
Cmax versus CFB in creatine kinase, n=45   -0.161 
Cmax versus triglycerides, n=45   0.134 
Cmax versus CFB in triglycerides, n=45   0.244 
Cmax versus lipase, n=45   -0.034 
Cmax versus CFB in lipase, n=45   0.115 
Cmax versus total cholesterol, n=45   -0.101 
Cmax versus CFB in total cholesterol, n=45   -0.192 
C0 versus AE occurrence, n=133   -0.080 
C0 versus maximum AE intensity, n=133   -0.003 
C0 versus ALT, n=133   -0.196 
C0 versus CFB in ALT, n=133   -0.237 
C0 versus total bilirubin, n=133   0.298 
C0 versus CFB in total bilirubin, n=133   0.120 
C0 versus creatine kinase, n=133   -0.094 
C0 versus CFB in creatine kinase, n=133   -0.093 
C0 versus triglycerides, n=133   -0.058 
C0 versus CFB in triglycerides, n=133   -0.012 
C0 versus lipase, n=133   -0.187 
C0 versus CFB in lipase, n=133   -0.137 
C0 versus total cholesterol, n=133   -0.179 
C0 versus CFB in total cholesterol, n=133   -0.125 
C0avg versus AE occurrence, n=140   -0.028 
C0avg versus maximum AE intensity, n=140   0.036 
C0avg versus ALT, n=140   -0.166 
C0avg versus CFB in ALT, n=140   -0.177 
C0avg versus total bilirubin, n=140   0.319 
C0avg versus CFB in total bilirubin, n=140   0.109 
C0avg versus creatine kinase, n=140   -0.114 
C0avg versus CFB in creatine kinase, n=140   -0.110 
C0avg versus triglycerides, n=140   0.057 
C0avg versus CFB in triglycerides, n=140   0.092 
C0avg versus lipase, n=140   -0.164 
C0avg versus CFB in lipase, n=140   -0.120 
C0avg versus total cholesterol, n=140   -0.170 
C0avg versus CFB in total cholesterol, n=140   -0.083 
Ctau versus AE occurrence, n=45   0.190 
Ctau versus maximum AE intensity, n=45   0.205 
Ctau versus ALT, n=45   -0.281 
Ctau versus CFB in ALT, n=45   -0.285 
Ctau versus total bilirubin, n=45   0.446 
Ctau versus CFB in total bilirubin, n=45   0.237 
Ctau versus creatine kinase, n=45   -0.143 
Ctau versus CFB in creatine kinase, n=45   -0.125 
Ctau versus triglycerides, n=45   0.061 
Ctau versus CFB in triglycerides, n=45   0.172 
Ctau versus lipase, n=45   -0.131 
Ctau versus CFB in lipase, n=45   0.056 
Ctau versus total cholesterol, n=45   -0.039 
Ctau versus CFB in total cholesterol, n=45   -0.108 
Cmin versus AE occurrence, n=45   0.156 
Cmin versus maximum AE intensity, n=45   0.193 
Cmin versus ALT, n=45   -0.236 
Cmin versus CFB in ALT, n=45   -0.253 
Cmin versus total bilirubin, n=45   0.430 
Cmin versus CFB in total bilirubin, n=45   0.171 
Cmin versus creatine kinase, n=45   -0.132 
Cmin versus CFB in creatine kinase, n=45   -0.124 
Cmin versus triglycerides, n=45   -0.042 
Cmin versus CFB in triglycerides, n=45   0.057 
Cmin versus lipase, n=45   -0.135 
Cmin versus CFB in lipase, n=45   0.032 
Cmin versus total cholesterol, n=45   -0.194 
Cmin versus CFB in total cholesterol, n=45   -0.208 

No statistical analysis provided for Relationship Between the Indicated Safety Parameters at Week 96 and the Indicated Plasma DTG PK Parameters



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
  Hide 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