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

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ClinicalTrials.gov Identifier: NCT01568892
Recruitment Status : Completed
First Posted : April 2, 2012
Results First Posted : February 19, 2014
Last Update Posted : June 5, 2018
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Quadruple (Participant, Care Provider, 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

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 
COMPLETED   7   13 
NOT COMPLETED   6   3 
Adverse Event                2                0 
Lack of Efficacy                4                2 
Lost to Follow-up                0                1 
[1] One participant completing the DB Phase withdrew on Day 8 and did not enter the Open-label Phase.



  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 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 
Overall Participants Analyzed 
[Units: Participants]
 14   16   30 
Age 
[Units: Years]
Mean (Standard Deviation)
 47.5  (11.56)   48.6  (8.85)   48.1  (10.04) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      2  14.3%      4  25.0%      6  20.0% 
Male      12  85.7%      12  75.0%      24  80.0% 
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

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; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84; and Follow-up (FU) ]

3.  Secondary:   Mean Change From Baseline in Plasma HIV-1 RNA Over Time   [ Time Frame: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84; and FU ]

4.  Secondary:   Number of Participants With Plasma HIV-1 RNA <50 c/mL Over Time   [ Time Frame: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48 ]

5.  Secondary:   Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time   [ Time Frame: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48 ]
  Hide Outcome Measure 5

Measure Type Secondary
Measure Title Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time
Measure Description Plasma samples were collected for quantitative HIV-1 RNA analysis at Baseline (Day 1); Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48. Number of participants with plasma HIV-1 RNA level <400 c/mL was obtained using FDA’s snapshot algorithm, where all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigational product prior to the visit window) were treated as non-responders. Also, participants who switch their concomitant ART prior to the visit of interest as follows were also treated as non-responders: background ART substitutions not permitted per protocol; background ART substitutions permitted per protocol; however the decision to switch is not documented as being before or at the first On-treatment visit after switching to OBR (i.e. Day 28) where HIV-1 RNA is assessed.
Time Frame Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40 and 48  

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 Snapshot dataset was used for analysis.

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 
Participants Analyzed   14   16 
Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time 
[Units: Participants]
   
Baseline   2   0 
Day 8   4   0 
Day 28   9   12 
Week 8   7   13 
Week 12   7   10 
Week 16   7   12 
Week 24   6   11 
Week 32   6   10 
Week 40   5   10 
Week 48   6   10 

No statistical analysis provided for Number of Participants With Plasma HIV-1 RNA <400 c/mL Over Time



6.  Secondary:   Absolute Values in Cluster of Differentiation 4+ (CD4+) Cell Counts Over Time   [ Time Frame: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84; and FU ]

7.  Secondary:   Median Change From Baseline in CD4+ Cell Counts Over Time   [ Time Frame: Baseline; Day 8; Day 28; Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72, and 84; and FU ]

8.  Secondary:   Absolute Values in Cluster of Differentiation 8+ (CD8+) Cell Counts Over Time   [ Time Frame: Baseline; Day 28; Weeks 12, 24, and 48 ]

9.  Secondary:   Median Change From Baseline in CD8+ Cell Counts Over Time   [ Time Frame: Baseline; Day 28; Weeks 12, 24, and 48 ]

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 Week 48 analysis cut-off date (median of 55 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 Week 48 analysis data cut-off date (median of 55 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 Week 48 analysis data cut-off date (median of 55 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 Week 48 analysis data cut-off date (median of 55 weeks) ]

14.  Secondary:   AUC(0-tau) of DTG   [ Time Frame: Day 8, Day 28, and Week 24 ]

15.  Secondary:   Cmax of DTG   [ Time Frame: Day 8, Day 28, and Week 24 ]

16.  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 ]

17.  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 Week 48 analysis data cut-off date (median of 55 weeks) ]

18.  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 Week 48 analysis data cut-off date (median of 55 weeks) ]

19.  Secondary:   Number of Participants Who Discontinued Study Treatment Due to AEs   [ Time Frame: From the first dose of study medication until early withdrawal or through the Week 48 analysis data cut-off date (median of 55 weeks) ]

20.  Secondary:   Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings   [ Time Frame: Up to Week 24 ]

21.  Secondary:   Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)   [ Time Frame: Baseline and Weeks 24 and 48 ]

22.  Secondary:   Change From Baseline in Heart Rate   [ Time Frame: Baseline and Weeks 24 and 48 ]

23.  Secondary:   Change From Baseline in Albumin Level   [ Time Frame: Baseline, Week 24 and 48 ]

24.  Secondary:   Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Creatine Kinase   [ Time Frame: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84 ]

25.  Secondary:   Change From Baseline in Total Bilirubin (T. Bil) and Creatinine Levels   [ Time Frame: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84 ]

26.  Secondary:   Change From Baseline in Cholesterol, Chloride, Carbon Dioxide (CO2)/Bicarbonate (HCO3), Glucose, High Density Lipoprotein Cholesterol, Potassium, Low Density Lipoprotein (LDL) Cholesterol, Sodium, Phosphorus, Triglycerides and Urea/Blood Urea Nitrogen   [ Time Frame: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84 ]

27.  Secondary:   Change From Baseline in Creatinine Clearance   [ Time Frame: Baseline, Day 8, Day 28, Week 16, Week 24, Week 32 and Week 48 ]

28.  Secondary:   Change From Baseline in Lipase Levels   [ Time Frame: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84 ]

29.  Secondary:   Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet and White Blood Cell (WBC) Count   [ Time Frame: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84 ]

30.  Secondary:   Change From Baseline in Hemoglobin Level   [ Time Frame: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84 ]

31.  Secondary:   Change From Baseline in Hematocrit Level   [ Time Frame: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84 ]

32.  Secondary:   Change From Baseline in Mean Corpuscle Volume   [ Time Frame: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84 ]

33.  Secondary:   Change From Baseline in Red Blood Cell Count   [ Time Frame: Baseline, Day 8, Day 28, Weeks 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84 ]


  Serious Adverse Events


  Other Adverse Events


  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