A Pilot Study Assessing the Integrase Inhibitor GSK1349572 in HIV-infected Persons With Virus Resistant to Raltegravir

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00950859
First received: July 23, 2009
Last updated: July 30, 2015
Last verified: July 2015
Results First Received: August 15, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus
Interventions: Drug: GSK1349572 (Cohort I)
Drug: GSK1349572 (Cohort II)

  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
Participants recruited initially to Cohort I and subsequently to Cohort II. Recruitment to Cohort I was closed 9 months before recruitment to Cohort II was opened. Recruitment was not randomized.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Cohort I (DTG 50 mg OD) Participants received dolutegravir (DTG) 50 milligrams (mg) once a day (OD).
Cohort II (DTG 50 mg BID) Participants received DTG 50 mg twice a day (BID).

Participant Flow:   Overall Study
    Cohort I (DTG 50 mg OD)     Cohort II (DTG 50 mg BID)  
STARTED     27     24  
COMPLETED     11     14  
NOT COMPLETED     16     10  
Adverse Event                 3                 3  
Insufficient Viral Load Response                 12                 3  
Protocol Violation                 1                 1  
Lost to Follow-up                 0                 3  



  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
Cohort I (DTG 50 mg OD) Participants received dolutegravir (DTG) 50 milligrams (mg) once a day (OD).
Cohort II (DTG 50 mg BID) Participants received DTG 50 mg twice a day (BID).
Total Total of all reporting groups

Baseline Measures
    Cohort I (DTG 50 mg OD)     Cohort II (DTG 50 mg BID)     Total  
Number of Participants  
[units: participants]
  27     24     51  
Age, Customized  
[units: Years]
Median (Full Range)
     
Years     48  
  (19 to 61)  
  47  
  (33 to 68)  
  47  
  (19 to 68)  
Gender  
[units: Participants]
     
Female     2     6     8  
Male     25     18     43  
Race/Ethnicity, Customized  
[units: Participants]
     
African American/African Heritage     3     5     8  
White-Arabic/North African Heritage     1     1     2  
White-White/Caucasian/European Heritage     23     18     41  



  Outcome Measures
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1.  Primary:   Number of Participants Who Achieved HIV-1 RNA <400 Copies (c)/Milliliter (mL) or at Least 0.7 log10 c/mL Below Their Baseline Value at Day 11   [ Time Frame: Baseline (Day 1) and Day 11 ]

2.  Secondary:   Mean Change From Baseline in Plasma HIV-1 RNA at Day 6 to 8, Day 11, Weeks 4, 12, 24, 48, 72, 96, From Week 108 Every 12 Weeks up to Study Completion   [ Time Frame: Baseline; Day 6 to 8; Day 11; Weeks 4, 12, 24, 48, 72, 96, from 108 every 12 weeks up to study completion ]

3.  Secondary:   Number of Participants Who Achieved Plasma HIV-1 RNA <400 c/mL and <50 c/mL at Baseline and Weeks 4, 12, 24, 48, 72, and 96: TLOVR Analysis.   [ Time Frame: Baseline; Weeks 4, 12, 24, 48, 72, and 96 ]

4.  Secondary:   Proportion of Participants Who Achieved Plasma HIV-1 RNA <400 c/mL and <50 c/mL From Week 48 Every 12 Weeks up to Study Completion   [ Time Frame: From Week 48 every 12 weeks up to study completion ]

5.  Secondary:   Change From Baseline in CD4+ Cell Count at Day 11 and Weeks 4, 12, 24, 48, 72, 96, Week 108 Every 12 Weeks up to Study Completion   [ Time Frame: Baseline; Day 11; Weeks 4, 12, 24, 48, 72, 96, from Week 108 every 12 weeks up to study completion ]

6.  Secondary:   Cmax, Cmin, and Ctau of DTG   [ Time Frame: Day 10 ]

7.  Secondary:   C0 Assessment of DTG   [ Time Frame: Day 10; Weeks 4 and 24 ]

8.  Secondary:   Tmax of DTG   [ Time Frame: Day 10 ]

9.  Secondary:   AUC0-24 Assessment of DTG   [ Time Frame: Day 10 ]

10.  Secondary:   Number of Participants With the Indicated HIV-1 Associated Conditions, Excluding Recurrences   [ Time Frame: From the day of the first dose of study drug until study completion (median 605 days for Cohort I, median 1181 days for Cohort II) ]

11.  Secondary:   Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shifts to CDC Class C or Death   [ Time Frame: From the day of the first dose of study drug until study completion (median 605 days for Cohort I, median 1181 days for Cohort II) ]

12.  Secondary:   Number of Participants (Cumulative) With Protocol-defined Virological Failure (PDVF) at Day 11 and Weeks 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84, 96, Week 108 Every 12 Weeks up to Study Completion   [ Time Frame: Day 11; Weeks 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84, 96, from Week 108 every 12 weeks up to study completion ]
  Hide Outcome Measure 12

Measure Type Secondary
Measure Title Number of Participants (Cumulative) With Protocol-defined Virological Failure (PDVF) at Day 11 and Weeks 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84, 96, Week 108 Every 12 Weeks up to Study Completion
Measure Description PDVF is defined in relation to Baseline plasma HIV-1 RNA levels: at Day 11, a decrease of <0.7 log10 c/mL unless <400 c/mL; at Weeks 8 to <16, a decrease of <1.0 log10 c/mL unless <400 c/mL or an increase of >= 1.0 log10 c/mL from nadir; and at or after Week 16, ≥400 c/mL. PDVF at Day 11 was based on a single plasma HIV-1 RNA evaluation and did not require confirmation. Confirmation testing was required for visits at or after Week 8. For the combination treatment phase, all HIV-1 RNA samples that meet a criterion for suspected PDVF must be confirmed by a second measurement performed at least 1 week but not more than 4 weeks apart from the date of the original sample.
Time Frame Day 11; Weeks 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84, 96, from Week 108 every 12 weeks up to study completion  
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.
ITT-E Population

Reporting Groups
  Description
Cohort I (DTG 50 mg OD) Participants received dolutegravir (DTG) 50 milligrams (mg) once a day (OD).
Cohort II (DTG 50 mg BID) Participants received DTG 50 mg twice a day (BID).

Measured Values
    Cohort I (DTG 50 mg OD)     Cohort II (DTG 50 mg BID)  
Number of Participants Analyzed  
[units: participants]
  27     24  
Number of Participants (Cumulative) With Protocol-defined Virological Failure (PDVF) at Day 11 and Weeks 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84, 96, Week 108 Every 12 Weeks up to Study Completion  
[units: Participants]
   
Day 11     6     1  
Week 8     7     3  
Week 12     9     3  
Week 16     10     5  
Week 20     10     5  
Week 24     12     5  
Week 32     12     5  
Week 40     12     5  
Week 48     13     5  
Week 60     13     5  
Week 72     14     6  
Week 84     15     6  
Week 96     16     6  
Week 108     16     6  
Week 120     16     6  
Week 132     16     6  
Week 144     16     7  
Week 156     16     7  
Week 168     16     7  
Week 180     16     7  
Week 192     16     7  
Week 204     16     7  
Week 216     17     7  
Week 228     18     7  
Week 240     18     NA [1]
Week 252     18     NA [1]
Week 264     18     NA [1]
[1] No data were available for analysis from Cohort II at the time points.

No statistical analysis provided for Number of Participants (Cumulative) With Protocol-defined Virological Failure (PDVF) at Day 11 and Weeks 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84, 96, Week 108 Every 12 Weeks up to Study Completion



13.  Secondary:   Number of Participants With the Indicated Genotypic Resistance at Baseline   [ Time Frame: Baseline ]

14.  Secondary:   Median Fold Change in Sensitivity to DTG by the Baseline (Day 1) IN Mutational Group   [ Time Frame: Baseline (Day 1) ]

15.  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 (Day 1) until study completion (median 605 days for Cohort I, median 1181 days for Cohort II) ]

16.  Secondary:   Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance   [ Time Frame: From Baseline (Day 1) until study completion (median 605 days for Cohort I, median 1181 days for Cohort II) ]

17.  Secondary:   Number of Participants With the Indicated Grade 3 and Grade 4 Clinical Chemistry Toxicities   [ Time Frame: From the day of the first dose of study drug until study completion (median 605 days for Cohort I, median 1181 days for Cohort II) ]

18.  Secondary:   Number of Participants With the Indicated Grade 3 and Grade 4 Hematological Toxicities   [ Time Frame: From Baseline (Day 1) until study completion (median 605 days for Cohort I, median 1181 days for Cohort II) ]


  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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