Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

A Study of the Pharmacokinetics and Antiviral Activity of Dolutegravir in the Central Nervous System in HIV-1 Infected ART-naive Subjects

This study has been completed.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01499199
First received: December 15, 2011
Last updated: January 15, 2015
Last verified: January 2015
Results First Received: August 15, 2013  
Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus
Intervention: Drug: Dolutegravir

  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
Eligible participants received dolutegravir (DTG ) 50 milligrams (mg) once daily (OD) in combination with abacavir/lamivudine (ABC/3TC) for 96 weeks.

Reporting Groups
  Description
Dolutegravir 50 mg OD Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) in combination with abacavir/lamivudine (ABC/3TC) OD.

Participant Flow:   Overall Study
    Dolutegravir 50 mg OD  
STARTED     13  
COMPLETED     11  
NOT COMPLETED     2  
Adverse Event                 1  
Lack of Efficacy                 1  



  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
Dolutegravir 50 mg OD Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) in combination with abacavir/lamivudine (ABC/3TC) OD.

Baseline Measures
    Dolutegravir 50 mg OD  
Number of Participants  
[units: participants]
  13  
Age  
[units: Years]
Mean ± Standard Deviation
  40.2  ± 6.90  
Gender  
[units: Participants]
 
Female     0  
Male     13  
Race/Ethnicity, Customized  
[units: participants]
 
White     13  
Baseline plasma human immunodeficiency virus-1 (HIV-1) ribonucleic acid (RNA) [1]
[units: log10┬ácopies/mL]
Median ( Full Range )
  4.73  
  ( 3.60 to 6.57 )  
Number of participants with Baseline plasma HIV-1 RNA <=100000 copies/mL and >100000 copies/mL [2]
[units: Participants]
 
<=100000 copies/mL     8  
>100000 copies/mL     5  
[1] The absolute value of plasma HIV-1 RNA was measured at Baseline as log10 copies/milliliter (mL).
[2] The number of participants with Baseline plasma HIV-1 RNA <= 100000 copies/mL and >100000 copies/mL was measured.



  Outcome Measures
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1.  Primary:   The Ratio of Total and Unbound DTG Concentrations Between Cerebrospinal Fluid (CSF) and Plasma at Week 2 and Week 16   [ Time Frame: Week 2 and Week 16 ]

2.  Primary:   Total DTG Plasma Concentrations at Week 2 and Week 16   [ Time Frame: Week 2 and Week 16 ]

3.  Primary:   Unbound DTG Plasma Concentrations at Week 2 and Week 16   [ Time Frame: Week 2 and Week 16 ]

4.  Primary:   Plasma DTG Unbound Fraction at Week 2 and Week 16   [ Time Frame: Week 2 and Week 16 ]

5.  Primary:   DTG Concentrations in CSF at Weeks 2 and Week 16   [ Time Frame: Week 2 and Week 16 ]

6.  Secondary:   Number of Participants With Plasma HIV-1 RNA <50 Copies Per Milliliter (c/mL) at Baseline and Weeks 2, 4, 8, 12, and 16   [ Time Frame: Baseline; Weeks 2, 4, 8, 12, and 16 ]

7.  Secondary:   Absolute Values and Change From Baseline in Plasma Human Immunodeficiency Virus (HIV-1) Ribonucleic Acid (RNA) Levels at Weeks 2, 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, and 96   [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, and 96 ]

8.  Secondary:   Number of Participants With CSF HIV-1 RNA <50 Copies/Milliliter (c/mL) at Baseline, Week 2, and Week 16   [ Time Frame: Baseline, Week 2, and Week 16 ]

9.  Secondary:   Absolute Values and Change From Baseline in CSF HIV-1 RNA Levels at Week 2 and Week 16   [ Time Frame: Baseline, Week 2, and Week 16 ]

10.  Secondary:   Number of Participants With the Indicated Number of Copies of HIV-1 RNA in Both the CSF and Plasma at Baseline, Week 2, and Week 16   [ Time Frame: Baseline, Week 2, and Week 16 ]

11.  Secondary:   Pearson Correlation Between CSF DTG Concentration and Absolute Values and Change From Baseline (CFB) in CSF HIV-1 RNA at Week 2, Week 16, and Overall   [ Time Frame: From Baseline to Week 16 ]

12.  Secondary:   Absolute Values and Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, and 96   [ Time Frame: Baseline; Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, and 96 ]
  Hide Outcome Measure 12

Measure Type Secondary
Measure Title Absolute Values and Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, and 96
Measure Description The absolute value for CD4+ cell count (cells per millimeters cubed [mm^3]) was assessed at Baseline, Week 4, Week 8, Week 12, Week 16, Week 24, Week 36, Week 48, Week 60, Week 72, Week 84, and Week 96. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Baseline; Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, and 96  
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. Only those participants available at the indicated time point were assessed.

Reporting Groups
  Description
Dolutegravir 50 mg OD Participants received dolutegravir (DTG) 50 milligrams (mg) once daily (OD) in combination with abacavir/lamivudine (ABC/3TC) OD.

Measured Values
    Dolutegravir 50 mg OD  
Number of Participants Analyzed  
[units: participants]
  13  
Absolute Values and Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, and 96  
[units: cells/mm^3]
Median ( Full Range )
 
Absolute CD4+ cell count, Baseline, n=13     260  
  ( 152 to 863 )  
Absolute CD4+ cell count, Week 4, n=12     578  
  ( 374 to 903 )  
Absolute CD4+ cell count, Week 8, n=12     645  
  ( 364 to 1118 )  
Absolute CD4+ cell count, Week 12, n=12     589  
  ( 303 to 1144 )  
Absolute CD4+ cell count, Week 16, n=12     573  
  ( 436 to 1156 )  
Absolute CD4+ cell count, Week 24, n=12     634  
  ( 448 to 1339 )  
Absolute CD4+ cell count, Week (Wk) 36, n=11     706  
  ( 534 to 1351 )  
Absolute CD4+ cell count, Week 48, n=11     666  
  ( 537 to 939 )  
Absolute CD4+ cell count, Week 60, n=11     702  
  ( 567 to 1266 )  
Absolute CD4+ cell count, Week 72, n=11     823  
  ( 620 to 1315 )  
Absolute CD4+ cell count, Week 84, n=11     907  
  ( 512 to 1341 )  
Absolute CD4+ cell count, Week 96, n=11     843  
  ( 339 to 1436 )  
Change from Baseline CD4+ cell count, Week 4, n=12     162  
  ( -158 to 365 )  
Change from Baseline CD4+ cell count, Week 8, n=12     247  
  ( 44 to 551 )  
Change from Baseline CD4+ cell count, Wk 12, n=12     263  
  ( -17 to 500 )  
Change from Baseline CD4+ cell count, Wk 16, n=12     226  
  ( -248 to 629 )  
Change from Baseline CD4+ cell count, Wk 24, n=12     264  
  ( 86 to 762 )  
Change from Baseline CD4+ cell count, Wk 36, n=11     480  
  ( 174 to 774 )  
Change from Baseline CD4+ cell count, Wk 48, n=11     311  
  ( -80 to 541 )  
Change from Baseline CD4+ cell count, Wk 60, n=11     382  
  ( 5 to 708 )  
Change from Baseline CD4+ cell count, Wk 72, n=11     519  
  ( 260 to 651 )  
Change from Baseline CD4+ cell count, Wk 84, n=11     543  
  ( 94 to 792 )  
Change from Baseline CD4+ cell count, Wk 96, n=11     467  
  ( -65 to 859 )  

No statistical analysis provided for Absolute Values and Change From Baseline in Cluster of Differentiation 4+ (CD4+) Cell Counts at Weeks 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, and 96



13.  Secondary:   Absolute Values and Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at Weeks 4, 12, 16, 24, 48, and 96   [ Time Frame: Baseline; Weeks 4, 12, 16, 24, 48, and 96 ]

14.  Secondary:   Number of Participants With Post-Baseline HIV-1-associated Conditions, Including Recurrences   [ Time Frame: Baseline through the date the last participant completed Week 96 + follow-up visit (if applicable) ]

15.  Secondary:   The Numbers of Participants (Par.) With Clinical Adverse Events or Laboratory Abnormalities   [ Time Frame: Baseline (BL) through the date the last participant completed Week (W) 96 + the follow-up visit (if applicable) ]

16.  Secondary:   Number of Participants With Treatment-emergent Genotypic and Phenotypic Resistance to DTG and Other Antiretroviral Therapy (ART)   [ Time Frame: Baseline through the date the last participant completed Week 96 ]


  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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