Now Available for Public Comment: 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 is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Shionogi
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT01499199
First received: December 15, 2011
Last updated: December 5, 2013
Last verified: September 2013
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. The primary analysis was performed after the last participant completed 16 weeks on therapy; additional analyses were/are to be conducted after the last participant completed(s) Weeks 2 and 96.

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  
Ongoing     11 [1]
COMPLETED     0  
NOT COMPLETED     13  
Adverse Event                 1  
Lack of Efficacy                 1  
Ongoing                 11  
[1] A total of 11 participants were ongoing at the time of the interim analysis of the Week 16 data.



  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 copies/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 ]

Measure Type Primary
Measure Title The Ratio of Total and Unbound DTG Concentrations Between Cerebrospinal Fluid (CSF) and Plasma at Week 2 and Week 16
Measure Description Cerebrospinal fluid (CSF) is a clear, colorless bodily fluid produced in the choroid plexus of the brain. The CFS samples were collected at the Week 2 and Week 16 visits, within 1 hour of plasma pharmacokinetic (PK) sampling. The ratio (presented as a percentage) of CSF DTG concentration over paired plasma total DTG concentration (RCSF_plasma) was calculated at the Week 2 and Week 16 visits.
Time Frame Week 2 and Week 16  
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.
Plasma/CSF DTG Paired Sample Population: participants (par.) with plasma and CSF samples collected post-dose and within 1 hour of each other (one par. withdrew prior to Week 2 and did not contribute to PK assessments). One par. was excluded from the analysis at Week 2 because his/her paired samples were not collected within the specified timeframe.

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]
  12  
The Ratio of Total and Unbound DTG Concentrations Between Cerebrospinal Fluid (CSF) and Plasma at Week 2 and Week 16  
[units: percentage]
Median ( Full Range )
 
Week 2, n=11     0.516  
  ( 0.115 to 0.658 )  
Week 16, n=12     0.412  
  ( 0.299 to 2.04 )  

No statistical analysis provided for The Ratio of Total and Unbound DTG Concentrations Between Cerebrospinal Fluid (CSF) and Plasma at Week 2 and Week 16



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

Measure Type Primary
Measure Title Total DTG Plasma Concentrations at Week 2 and Week 16
Measure Description Total plasma DTG concentrations were calculated at the Week 2 and Week 16 visits.
Time Frame Week 2 and Week 16  
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.
Plasma DTG Concentration Population: all participants receiving DTG who underwent PK sampling during the study and provided evaluable DTG plasma concentration data

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]
  12  
Total DTG Plasma Concentrations at Week 2 and Week 16  
[units: Micrograms per milliliter (µg/mL)]
Median ( Full Range )
 
Week 2     3.36  
  ( 2.09 to 5.28 )  
Week 16     3.21  
  ( 0.64 to 4.92 )  

No statistical analysis provided for Total DTG Plasma Concentrations at Week 2 and Week 16



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

Measure Type Primary
Measure Title Unbound DTG Plasma Concentrations at Week 2 and Week 16
Measure Description Unbound (free, not bound to cellular proteins) plasma DTG concentrations were calculated at the Week 2 and Week 16 visits.
Time Frame Week 2 and Week 16  
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.
Plasma DTG Concentration Population

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]
  12  
Unbound DTG Plasma Concentrations at Week 2 and Week 16  
[units: Nanograms per milliliter (ng/mL)]
Median ( Full Range )
 
Week 2     17.1  
  ( 10.3 to 24.0 )  
Week 16     23.9  
  ( 3.81 to 32.1 )  

No statistical analysis provided for Unbound DTG Plasma Concentrations at Week 2 and Week 16



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

Measure Type Primary
Measure Title Plasma DTG Unbound Fraction at Week 2 and Week 16
Measure Description The unbound fraction of DTG in plasma (presented as a percentage of unbound [i.e., free DTG not bound to cellular proteins] DTG plasma concentration over paired plasma total DTG concentration) was calculated at the Week 2 and Week 16 visits.
Time Frame Week 2 and Week 16  
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.
Plasma DTG Concentration Population

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]
  12  
Plasma DTG Unbound Fraction at Week 2 and Week 16  
[units: Percentage]
Median ( Full Range )
 
Week 2     0.488  
  ( 0.333 to 0.655 )  
Week 16     0.701  
  ( 0.488 to 4.30 )  

No statistical analysis provided for Plasma DTG Unbound Fraction at Week 2 and Week 16



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

Measure Type Primary
Measure Title DTG Concentrations in CSF at Weeks 2 and Week 16
Measure Description CSF is a clear, colorless bodily fluid produced in the choroid plexus of the brain. The CFS samples were collected at the Week 2 and Week 16 visits, within 1 hour of plasma PK sampling. DTG concentration in CSF were calculated at the Week 2 and Week 16 visits.
Time Frame Week 2 and Week 16  
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.
CSF DTG Concentration Population: all participants receiving DTG who underwent lumbar puncture during the study and provided evaluable DTG CSF concentration data. One participant was excluded from the analysis at Week 2.

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]
  12  
DTG Concentrations in CSF at Weeks 2 and Week 16  
[units: Nanograms per milliliter (ng/mL)]
Median ( Full Range )
 
Week 2, n=11     18.2  
  ( 4.0 to 23.2 )  
Week 16, n=12     13.2  
  ( 3.7 to 18.3 )  

No statistical analysis provided for DTG Concentrations in CSF at Weeks 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 ]

Measure Type Secondary
Measure Title Number of Participants With Plasma HIV-1 RNA <50 Copies Per Milliliter (c/mL) at Baseline and Weeks 2, 4, 8, 12, and 16
Measure Description HIV-1 RNA response in plasma was measured as the number of participants with HIV-1 RNA less than 50 c/mL at Baseline, Week 2, Week 4, Week 8, Week 12, and Week 16.
Time Frame Baseline; Weeks 2, 4, 8, 12, and 16  
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.
Intent -to-Treat Exposed (ITT-E) Population: all participants who received at least one dose of investigational product

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  
Number of Participants With Plasma HIV-1 RNA <50 Copies Per Milliliter (c/mL) at Baseline and Weeks 2, 4, 8, 12, and 16  
[units: participants]
 
Baseline     0  
Week 2     4  
Week 4     6  
Week 8     8  
Week 12     10  
Week 16     10  

No statistical analysis provided for Number of Participants With Plasma HIV-1 RNA <50 Copies Per Milliliter (c/mL) at Baseline and 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, and 36   [ Time Frame: Baseline; Weeks 2, 4, 8, 12, 16, 24, and 36 ]

Measure Type Secondary
Measure Title 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, and 36
Measure Description The plasma samples were collected at the Week 2, Week 4, Week 8, Week 12, Week 16, Week 24, and Week 36 visits. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Baseline; Weeks 2, 4, 8, 12, 16, 24, and 36  
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. As the data cut for this analysis was after the last participant reached Week 16, there is limited data available at Week 24 and Week 36 because not all participants had the opportunity to reach these time points.

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 Plasma Human Immunodeficiency Virus (HIV-1) Ribonucleic Acid (RNA) Levels at Weeks 2, 4, 8, 12, 16, 24, and 36  
[units: log10 copies/mL]
Median ( Full Range )
 
Absolute value, Baseline, n=13     4.73  
  ( 3.60 to 6.57 )  
Absolute value, Week 2, n=12     2.05  
  ( 1.59 to 2.99 )  
Change from Baseline, Week 2, n=12     -2.53  
  ( -3.70 to -2.01 )  
Absolute value, Week 4, n=12     1.67  
  ( 1.59 to 2.49 )  
Change from Baseline, Week 4, n=12     -3.04  
  ( -4.08 to -2.01 )  
Absolute Value, Week 8, n=12     1.59  
  ( 1.59 to 2.48 )  
Change from Baseline, Week 8, n=12     -3.10  
  ( -4.09 to -2.01 )  
Absolute value, Week 12, n=12     1.59  
  ( 1.59 to 2.36 )  
Change from Baseline, Week 12, n=12     -3.04  
  ( -4.20 to -2.01 )  
Absolute value, Week 16, n=12     1.59  
  ( 1.59 to 2.37 )  
Change from Baseline, Week 16, n=12     -3.04  
  ( -4.19 to -2.01 )  
Absolute Value, Week 24, n=8     1.59  
  ( 1.59 to 2.21 )  
Change from Baseline, Week 24, n=8     -2.90  
  ( -4.35 to -2.01 )  
Absolute value, Week 36, n=2     1.59  
  ( 1.59 to 1.59 )  
Change from Baseline, Week 36, n=2     -2.88  
  ( -3.08 to -2.68 )  

No statistical analysis provided for 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, and 36



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 ]

Measure Type Secondary
Measure Title Number of Participants With CSF HIV-1 RNA <50 Copies/Milliliter (c/mL) at Baseline, Week 2, and Week 16
Measure Description The antiviral activity of dolutegravir in CSF over time was measured as the number of participants with HIV-1 RNA <50 copies/milliliter (c/mL).
Time Frame Baseline, Week 2, and Week 16  
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.
CSF Pharmacodynamic Population: all participants who received DTG and underwent lumbar puncture during the study and provided CSF HIV-1 RNA data. Only those participants available at the indicated time points 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  
Number of Participants With CSF HIV-1 RNA <50 Copies/Milliliter (c/mL) at Baseline, Week 2, and Week 16  
[units: participants]
 
Baseline, n=13     1  
Week 2, n=12     7  
Week 16, n=11     11  

No statistical analysis provided for Number of Participants With CSF HIV-1 RNA <50 Copies/Milliliter (c/mL) at 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 ]

Measure Type Secondary
Measure Title Absolute Values and Change From Baseline in CSF HIV-1 RNA Levels at Week 2 and Week 16
Measure Description The antiviral activity of dolutegravir in CSF over time was measured as absolute values and change from Baseline in HIV-1 RNA levels in CSF at Week 2 and Week 16. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Baseline, Week 2, and Week 16  
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.
CSF Pharmacodynamic Population. Only those participants available at the indicated time points 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 CSF HIV-1 RNA Levels at Week 2 and Week 16  
[units: log10 c/mL]
Median ( Full Range )
 
Absolute value, Baseline, n=13     3.64  
  ( 1.46 to 5.60 )  
Absolute value, Week 2, n=12     0.98  
  ( 0.00 to 3.30 )  
Change from Baseline, Week 2, n=12     -2.19  
  ( -3.11 to -1.29 )  
Absolute value, Week 16, n=11     0.00  
  ( 0.00 to 0.70 )  
Change from Baseline, Week 16, n=11     -3.42  
  ( -5.60 to -1.46 )  

No statistical analysis provided for Absolute Values and Change From Baseline in CSF HIV-1 RNA Levels at 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 ]

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  
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.
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  
Number of 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 ]

Measure Type Secondary
Measure Title 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
Measure Description The Pearson Correlation Coefficient is a measure of the correlation between CSF DTG concentrations and absolute values/changes from Baseline in CSF HIV-1 RNA at Week 2 and Week 16. CSF HIV-1 RNA is measured as log10 copies per milliliter (copies/mL).
Time Frame From Baseline to Week 16  
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.
CSF Pharmacodynamic Population. The overall analysis combines Week 2 and Week 16 data; thus, analysis was performed on 22 data points from 11 participants.

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]
  11  
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  
[units: Pearson Correlation Coefficient]
Mean ( 90% Confidence Interval )
 
Week 2, Absolute Log10 CSF HIV-1 RNA, n=11     0.567  
  ( 0.062 to 0.841 )  
Week 2, CFB Log10 CSF HIV-1, n=11     0.007  
  ( -0.518 to 0.529 )  
Week 16, Absolute Log10 CSF HIV-1 RNA, n=11     -0.775  
  ( -0.924 to -0.423 )  
Week 16, CFB Log10 CSF HIV-1, n=11     -0.354  
  ( -0.740 to 0.209 )  
Overall, Absolute Log10 CSF HIV-1 RNA, n=11     0.517  
  ( 0.193 to 0.740 )  
Overall, CFB Log10 CSF HIV-1, n=11     0.106  
  ( -0.265 to 0.449 )  

No statistical analysis provided for 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



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

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, and 36
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, and Week 36. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
Time Frame Baseline; Weeks 4, 8, 12, 16, 24, and 36  
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. As the data cut for this analysis was after the last participant reached Week 16, there is limited data available at Week 24 and Week 36 because not all participants had the opportunity to reach these time points.

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, and 36  
[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=8     781  
  ( 523 to 1016 )  
Absolute CD4+ cell count, Week (Wk) 36, n=2     838  
  ( 546 to 1129 )  
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=8     250  
  ( 86 to 619 )  
Change from Baseline CD4+ cell count, Wk 36, n=2     403  
  ( 226 to 580 )  

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, and 36



13.  Secondary:   Number of Participants With Post-Baseline HIV-1-associated Conditions, Including Recurrences   [ Time Frame: Baseline through the date the last participant completed Week 16 (a limited number of participants completed the Week 24 and 36 visits) ]

Measure Type Secondary
Measure Title Number of Participants With Post-Baseline HIV-1-associated Conditions, Including Recurrences
Measure Description The number of participants who reported a new or recurrent Centers for Disease Control and Prevention (CDC) Class B or Class C condition was assessed from Baseline though the date the last participant completed Week 16. Category (CAT) A: one or more of the following conditions (CON), without any CON listed in Categories B and C: asymptomatic HIV infection, persistent generalized lymphadenopathy, acute (primary) HIV infection with accompanying illness or history of acute HIV infection. CAT B: symptomatic CON that are attributed to HIV infection or are indicative of a defect in cell-mediated immunity; or that are considered by physicians to have a clinical course or to require management that is complicated by HIV infection; and not included among CON listed in clinical CAT C. CAT C: the clinical CON listed in the AIDS surveillance case definition.
Time Frame Baseline through the date the last participant completed Week 16 (a limited number of participants completed the Week 24 and 36 visits)  
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

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  
Number of Participants With Post-Baseline HIV-1-associated Conditions, Including Recurrences  
[units: participants]
 
New CDC Category B event     0  
Recurring CDC Category B event     0  
New CDC Category C event     0  
Recurring CDC Category C event     0  

No statistical analysis provided for Number of Participants With Post-Baseline HIV-1-associated Conditions, Including Recurrences



14.  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) 16 (a limited number of participants completed the Week 24 and 36 visits) ]

Measure Type Secondary
Measure Title The Numbers of Participants (Par.) With Clinical Adverse Events or Laboratory Abnormalities
Measure Description An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Refer to the general Adverse AE/SAE module for a complete list of AEs/SAEs. Any abnormal laboratory test result (hematology, clinical chemistry, or urinalysis) or other safety assessments (e.g., electrocardiograms [ECGs], radiological scans, vital sign measurements), including those that worsen from Baseline, and were felt to be clinically significant in the medical and scientific judgment of the investigator, were recorded as AEs or SAEs. Clinically suspected cases of hypersensitivity to ABC were also SAEs.
Time Frame Baseline (BL) through the date the last participant completed Week (W) 16 (a limited number of participants completed the Week 24 and 36 visits)  
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.
Safety Population: all participants who received at least one dose of study medication. Participants were analyzed according to the actual treatments received. Participants were not excluded from this population as a result of changes to the background regimen.

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  
The Numbers of Participants (Par.) With Clinical Adverse Events or Laboratory Abnormalities  
[units: participants]
 
Any AE     13  
Clinical chemistry toxicities     9  
Hematology toxicities     1  
Urinalysis     NA [1]
Abnormal ECG (clinically significant)     NA [2]
[1] Data are not collected until W 24 for comparison with Baseline levels. As this is the W 16 report, there are no relevant data to present; a limited number of par. had completed the W 24 visit as of the cut-off for the last par. completing W 16.
[2] ECG data, other than for the par. prematurely withdrawing, are not collected until W 48. As this is the W 16 report, there are no relevant data to present; no par. had completed the W 48 visit as of the cut-off for the last par. completing W 16.

No statistical analysis provided for The Numbers of Participants (Par.) With Clinical Adverse Events or Laboratory Abnormalities



15.  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 16 (a limited number of participants completed the Week 24 and Week 36 visits) ]

Measure Type Secondary
Measure Title Number of Participants With Treatment-emergent Genotypic and Phenotypic Resistance to DTG and Other Antiretroviral Therapy (ART)
Measure Description The number of participants with treatment-emergent genotypic and phenotypic resistance to integrase inhibitors (INIs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transctiptase inhibitors (NNRTIs), and protease inhibitors (PIs) was assessed.
Time Frame Baseline through the date the last participant completed Week 16 (a limited number of participants completed the Week 24 and Week 36 visits)  
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.
Protocol Defined Virologic Failure (PDVF) Genotypic Population (Integrase inhibitor [IN] Results at Baseline and PDVF): The PDVF Genotypic and Phenotypic populations consisted of all participants in the ITT-E Population with available on-treatment genotypic and phenotypic resistance data, respectively, at the time of PDVF

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  
Number of Participants With Treatment-emergent Genotypic and Phenotypic Resistance to DTG and Other Antiretroviral Therapy (ART)  
[units: participants]
 
Treatment-emergent genotypic resistance     0  
Treatment-emergent phenotypic resistance     0  

No statistical analysis provided for Number of Participants With Treatment-emergent Genotypic and Phenotypic Resistance to DTG and Other Antiretroviral Therapy (ART)



16.  Secondary:   Absolute Values and Change From Baseline in Cluster of Differentiation 8+ (CD8+) Cell Counts at Weeks 4, 12, 16, and 24   [ Time Frame: Baseline; Weeks 4, 12, 16, and 24 ]
Results not yet reported.   Anticipated Reporting Date:   08/2014   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
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