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Study Assessing Dolutegravir in HIV-1 Infected Subjects With Virus Resistant to Raltegravir and/or Elivitegravir (VIKING-4)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01568892
First received: March 29, 2012
Last updated: January 2, 2014
Last verified: December 2013
Results First Received: August 15, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus
Interventions: Drug: dolutegravir 50 mg twice daily
Drug: dolutegravir placebo twice daily
Drug: Open-label dolutegravir 50mg twice daily

  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
Participants (par.) meeting eligibility criteria at screening entered a 7-day randomized, double-blind, placebo-controlled phase. At Day 8, all par. entered an open-label phase and continued to receive dolutegravir with an optimized background regimen. A total of 75 par. were screened; 45 par. were screen failures, and 30 par. were randomized.

Reporting Groups
  Description
DTG 50 mg BID Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.

Participant Flow for 2 periods

Period 1:   Double-blind Phase
    DTG 50 mg BID     Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase  
STARTED     14     16  
COMPLETED     14     16  
NOT COMPLETED     0     0  

Period 2:   Open-label Phase
    DTG 50 mg BID     Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase  
STARTED     13 [1]   16  
Ongoing     12     15  
COMPLETED     0     0  
NOT COMPLETED     13     16  
Adverse Event                 1                 0  
Lack of Efficacy                 0                 1  
Ongoing                 12                 15  
[1] One participant completing the DB Phase withdrew on Day 8 and did not enter the Open-label Phase.



  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 50 mg BID Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Total Total of all reporting groups

Baseline Measures
    DTG 50 mg BID     Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase     Total  
Number of Participants  
[units: participants]
  14     16     30  
Age  
[units: Years]
Mean ± Standard Deviation
  47.5  ± 11.56     48.6  ± 8.85     48.1  ± 10.04  
Gender  
[units: Participants]
     
Female     2     4     6  
Male     12     12     24  
Race/Ethnicity, Customized  
[units: participants]
     
African American/African Heritage     8     8     16  
American Indian or Alaska Native     0     1     1  
White - Arabic/North African Heritage     1     0     1  
White - White/Caucasian/European Heritage     4     7     11  
Missing: None of the Available Races Applied     1     0     1  



  Outcome Measures
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1.  Primary:   Mean Change From Baseline in Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) at Day 8   [ Time Frame: Baseline and Day 8 ]

2.  Secondary:   Absolute Values in Plasma HIV-1 RNA Over Time   [ Time Frame: Baseline, Day 8, Day 28, and Week 8 ]

3.  Secondary:   Mean Change From Baseline in Plasma HIV-1 RNA Over Time   [ Time Frame: Baseline, Day 8, Day 28, and Week 8 ]

4.  Secondary:   Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time   [ Time Frame: Baseline, Day 8, Day 28, and Week 8 ]
  Hide Outcome Measure 4

Measure Type Secondary
Measure Title Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time
Measure Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1), Day 8, Day 28, and Week 8, using the Food and Drug Administration's Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (VOI [due to missing data/discontinuation of investigational product prior to the visit window]) as nonresponders, as well as participants who switched their concomitant antiretroviral (ART) prior to the VOI as follows: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol, however the decision to switch was not documented as being before or at the first on-treatment visit after switching to optimized background regimen (i.e., Week 4) where HIV-1 RNA was assessed. Otherwise, virologic success/failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the VOI analysis window.
Time Frame Baseline, Day 8, Day 28, and Week 8  
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. The Observed Case dataset, in which only the data that are available at a particular time point are used, with no imputation for missing values, was used for analysis. Only those participants available at the specified time points were analyzed.

Reporting Groups
  Description
DTG 50 mg BID Participants received dolutegravir (DTG) 50 milligrams (mg) twice daily (BID) and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the Double-blind (DB) Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.
Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase Participants received matching placebo BID and the components of their current failing antiretroviral regimen, except raltegravir or elvitegravir, for 7 days during the DB Phase. From Day 8, all participants continued to receive DTG 50 mg BID with an optimized background regimen in the Open-label Phase.

Measured Values
    DTG 50 mg BID     Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase  
Number of Participants Analyzed  
[units: participants]
  14     16  
Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time  
[units: participants]
   
Baseline, n=14, 16     0     0  
Day 8, n=14, 16     1     0  
Day 28, n=13, 16     6     6  
Week 8, n=9, 14     3     8  

No statistical analysis provided for Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time



5.  Secondary:   Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time   [ Time Frame: Baseline, Day 8, Day 28, and Week 8 ]

6.  Secondary:   Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time   [ Time Frame: Baseline, Day 8, Day 28, and Week 8 ]

7.  Secondary:   Median Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time   [ Time Frame: Baseline, Day 8, Day 28, and Week 8 ]

8.  Secondary:   Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts at Baseline and Day 28   [ Time Frame: Baseline and Day 28 ]

9.  Secondary:   Median Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at Day 28   [ Time Frame: Baseline and Day 28 ]

10.  Secondary:   Number of Participants With the Indicated Type of HIV-1 Disease Progression (Acquired Immunodeficiency Syndrome [AIDS] or Death [DT])   [ Time Frame: From the day of the first dose of study drug until early withdrawal or the Day 8 analysis cut-off date (average of 14 study weeks) ]

11.  Secondary:   Number of Participants With Any Adverse Event (Serious and Non-serious) of the Indicated Grade   [ Time Frame: From the first dose of study medication until early withdrawal or through the Day 8 analysis data cut-off date (average of 14 study weeks) ]

12.  Secondary:   Number of Participants With the Maximum Post-Baseline-emergent Clinical Chemistry Toxicities of the Indicated Grade   [ Time Frame: From the first dose of study medication until early withdrawal or through the Day 8 analysis data cut-off date (average of 14 study weeks) ]

13.  Secondary:   Number of Participants With the Maximum Post-Baseline-emergent Hematology Toxicities of the Indicated Grade   [ Time Frame: From the first dose of study medication until early withdrawal or through the Day 8 analysis data cut-off date (average of 14 study weeks) ]

14.  Secondary:   Plasma DTG Pre-dose Concentration (C0) at Day 8, Day 28, and Week 24; and Average DTG C0 (C0 Avg) at Week 24   [ Time Frame: Day 8, Day 28, and Week 24 ]

15.  Secondary:   Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Defined Virologic Failure (PDVF), as a Measure of Genotypic Resistance   [ Time Frame: From the first dose of study medication until early withdrawal or through the Day 8 analysis data cut-off date (average of 96 study days) ]

16.  Secondary:   Number of Participants With the Indicated Fold Increase in Fold Change (FC) in the 50% Inhibitory Concentration Relative to Wild-type Virus for DTG (i.e. PDVF FC/Baseline FC Ratio) at the Time of PDVF, as a Measure of Phenotypic Resistance   [ Time Frame: From the first dose of study medication until early withdrawal or through the Day 8 analysis data cut-off date (average of 96 study days) ]

17.  Secondary:   AUC(0-tau) of DTG   [ Time Frame: Day 8, Day 28, and Week 24 ]
Results not yet reported.   Anticipated Reporting Date:   12/2014   Safety Issue:   No

18.  Secondary:   Cmax of DTG   [ Time Frame: Day 8, Day 28, and Week 24 ]
Results not yet reported.   Anticipated Reporting Date:   12/2014   Safety Issue:   No


  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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  More Information
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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: GlaxoSmithKline
phone: 866-435-7343


No publications provided


Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01568892     History of Changes
Other Study ID Numbers: 116529
Study First Received: March 29, 2012
Results First Received: August 15, 2013
Last Updated: January 2, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board