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 ]

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 posted.   Anticipated Posting Date:   12/2014   Safety Issue:   No

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


  Serious Adverse Events


  Other Adverse Events
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Time Frame Serious adverse events (SAEs) and non-serious AEs were collected in the time period 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).
Additional Description SAEs and AEs were collected in members of Safety Population, comprised of all randomized participants who received at least one dose of study medication.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
DTG 50mg 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.

Other Adverse Events
    DTG 50mg BID     Placebo BID in DB Phase; DTG 50 mg BID in Open-label Phase  
Total, other (not including serious) adverse events      
# participants affected / at risk     9/14     8/16  
Blood and lymphatic system disorders      
Lymphadenopathy † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Cardiac disorders      
Cardiomyopathy † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Eye disorders      
Dry eye † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Gastrointestinal disorders      
Diarrhoea † 1    
# participants affected / at risk     2/14 (14.29%)     2/16 (12.50%)  
Nausea † 1    
# participants affected / at risk     3/14 (21.43%)     1/16 (6.25%)  
Abdominal pain upper † 1    
# participants affected / at risk     2/14 (14.29%)     0/16 (0.00%)  
Vomiting † 1    
# participants affected / at risk     1/14 (7.14%)     1/16 (6.25%)  
Abdominal pain † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Constipation † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Dehydration † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Dry mouth † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
General disorders      
Asthenia † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Chest pain † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Fatigue † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Injection site induration † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Injection site pain † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Pyrexia † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Infections and infestations      
Upper respiratory tract infection † 1    
# participants affected / at risk     1/14 (7.14%)     2/16 (12.50%)  
Hepatitis B † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Influenza † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Otitis media † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Urinary tract infection † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Vaginal abscess † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Injury, poisoning and procedural complications      
Fall † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Thermal burn † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Musculoskeletal and connective tissue disorders      
Muscle spasms † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Musculoskeletal chest pain † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Neck pain † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Pain in extremity † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Nervous system disorders      
Headache † 1    
# participants affected / at risk     3/14 (21.43%)     1/16 (6.25%)  
Dizziness † 1    
# participants affected / at risk     2/14 (14.29%)     0/16 (0.00%)  
Syncope † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Psychiatric disorders      
Anxiety † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Depression † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Libido decreased † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Mood altered † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Renal and urinary disorders      
Nephrolithiasis † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Nephropathy toxic † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Renal failure † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Reproductive system and breast disorders      
Breast enlargement † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Erectile dysfunction † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Respiratory, thoracic and mediastinal disorders      
Asthma † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Chronic obstructive pulmonary disease † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Cough † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Skin and subcutaneous tissue disorders      
Macule † 1    
# participants affected / at risk     0/14 (0.00%)     1/16 (6.25%)  
Skin irritation † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Vascular disorders      
Hypertension † 1    
# participants affected / at risk     1/14 (7.14%)     0/16 (0.00%)  
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA



  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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