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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00950859
First received: July 23, 2009
Last updated: January 9, 2014
Last verified: November 2013
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
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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  
Ongoing     13     19  
COMPLETED     0     0  
NOT COMPLETED     27     24  
Adverse Event                 2                 2  
Insufficient Viral Load Response                 12                 2  
Protocol Violation                 0                 1  
Ongoing                 13                 19  



  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.
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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 ]
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Measure Type Primary
Measure Title 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
Measure Description The number of participants who acheived Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) <400 c/mL or at least 0.7 log10 c/mL below their Baseline value at Day 11 was assessed. The last observation was carried forward if a participant had missed the Day 11 visit. The Baseline observation was carried forward if a participant had discontinued the treatment before Day 11. Blood samples for assessment of HIV-1 RNA levels were collected at Baseline and Day 11.
Time Frame Baseline (Day 1) and Day 11  
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.
Intent-to-Treat Exposed (ITT-E) Population: all participants who received at least one dose of study medication and who had at least one post-Baseline measure of plasma HIV-1 RNA.

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 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  
[units: Participants]
  21     23  


Statistical Analysis 1 for 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
Groups [1] Cohort I (DTG 50 mg OD)
percentage of participants [2] 78
95% Confidence Interval ( 58 to 91 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  The estimated value represents the percentage of participants with HIV-1 RNA <400 c/mL or at least 0.7 log10 c/mL below their Baseline value at Day 11.

Statistical Analysis 2 for 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
Groups [1] Cohort II (DTG 50 mg BID)
percentage of participants [2] 96
95% Confidence Interval ( 79 to 100 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant estimation information:
  The estimated value represents the percentage of participants with HIV-1 RNA <400 c/mL or at least 0.7 log10 c/mL below their Baseline value at Day 11.



2.  Secondary:   Mean Change From Baseline in Plasma HIV-1 RNA at Day 6 to 8, Day 11, and Weeks 4, 12, 24, 48, 72, and 96   [ Time Frame: Baseline; Day 6 to 8; Day 11; Weeks 4, 12, 24, 48, 72, and 96 ]

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:   Change From Baseline in CD4+ Cell Count at Day 11 and Weeks 4, 12, 24, 48, 72, and 96   [ Time Frame: Baseline; Day 11; Weeks 4, 12, 24, 48, 72, and 96 ]

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

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

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

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

9.  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 to the data cut-off (median 86 weeks for Cohort I, median 49 weeks for Cohort II ]

10.  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 to the data cut-off (median 86 weeks for Cohort I, median 49 weeks for Cohort II ]

11.  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, and 96   [ Time Frame: Day 11; Weeks 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96 ]

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

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

14.  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) to the data cut-off (median 86 weeks for Cohort I, median 49 weeks for Cohort II) ]

15.  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) to the data cut-off (median 86 weeks for Cohort I, median 49 weeks for Cohort II) ]

16.  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 to the data cut-off (median 86 weeks for Cohort I, median 49 weeks for Cohort II) ]

17.  Secondary:   Number of Participants With the Indicated Grade 3 and Grade 4 Hematological Toxicities   [ Time Frame: From Baseline (Day 1) to the data cut-off (median 86 weeks for Cohort I, median 49 weeks 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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