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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:
ClinicalTrials.gov Identifier:
NCT01499199
First Posted: December 26, 2011
Last Update Posted: February 25, 2015
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
Results First Submitted: August 15, 2013  
Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment;   Masking: None (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 
Overall Participants Analyzed 
[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 copies/mL]
Median (Full Range)
 4.73 
 (3.60 to 6.57) 
[1] The absolute value of plasma HIV-1 RNA was measured at Baseline as log10 copies/milliliter (mL).
Number of participants with Baseline plasma HIV-1 RNA <=100000 copies/mL and >100000 copies/mL [1] 
[Units: Participants]
 
<=100000 copies/mL   8 
>100000 copies/mL   5 
[1] 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 ]
  Hide Outcome Measure 10

Measure Type Secondary
Measure Title 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
Measure Description The relationship between HIV-1 RNA suppression in plasma and the CSF was measured as a comparison and as a change in the number of participants in the cross tabulation of <50 copies/mL in plasma, <50 copies/mL in CSF, >=50 copies/mL in plasma, and >=50 copies/mL in CSF at Baseline, Week 2, and Week 16.
Time Frame Baseline, Week 2, and Week 16  

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.
CSF Pharmacodynamic 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 
Participants Analyzed 
[Units: Participants]
 13 
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 
[Units: Participants]
 
Baseline, CSF<50 c/mL, Plasma<50 c/mL, n=13   0 
Baseline, CSF<50 c/mL, Plasma>=50 c/mL, n=13   1 
Baseline, CSF>=50 c/mL, Plasma<50 c/mL, n=13   0 
Baseline, CSF>=50 c/mL, Plasma>=50 c/mL, n=13   12 
Week 2, CSF<50 c/mL, Plasma<50 c/mL, n=12   4 
Week 2, CSF<50 c/mL, Plasma>=50 c/mL, n=12   3 
Week 2, CSF>=50 c/mL, Plasma<50 c/mL, n=12   0 
Week 2, CSF>=50 c/mL, Plasma>=50 c/mL, n=12   5 
Week 16, CSF<50 c/mL, Plasma<50 c/mL, n=11   9 
Week 16, CSF<50 c/mL, Plasma>=50 c/mL, n=11   2 
Week 16, CSF>=50 c/mL, Plasma<50 c/mL, n=11   0 
Week 16, CSF>=50 c/mL, Plasma>=50 c/mL, n=11   0 

No statistical analysis provided for 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



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 ]

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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  More Information