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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 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┬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, and 36   [ Time Frame: Baseline; 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 ]

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, and 36   [ Time Frame: Baseline; 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) ]

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) ]

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) ]

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
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Time Frame Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the date the last participant completed Week 16 (a limited number of participants completed the Week 24 and 36 visits).
Additional Description SAEs and non-serious AEs were reported for members of the Safety Population, comprised of all participants randomized to treatment who received at least one dose of trial medication during the treatment period.

Frequency Threshold
Threshold above which other adverse events are reported   0%  

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.

Other Adverse Events
    Dolutegravir 50 mg OD  
Total, other (not including serious) adverse events    
# participants affected / at risk     13/13  
Blood and lymphatic system disorders    
Anaemia † 1  
# participants affected / at risk     1/13 (7.69%)  
Eye disorders    
Eye pruritus † 1  
# participants affected / at risk     1/13 (7.69%)  
Gastrointestinal disorders    
Diarrhoea † 1  
# participants affected / at risk     2/13 (15.38%)  
Nausea † 1  
# participants affected / at risk     2/13 (15.38%)  
Abdominal distension † 1  
# participants affected / at risk     1/13 (7.69%)  
Constipation † 1  
# participants affected / at risk     1/13 (7.69%)  
Dyspepsia † 1  
# participants affected / at risk     1/13 (7.69%)  
Food poisoning † 1  
# participants affected / at risk     1/13 (7.69%)  
Gastrooesophageal reflux disease † 1  
# participants affected / at risk     1/13 (7.69%)  
Haemorrhoids † 1  
# participants affected / at risk     1/13 (7.69%)  
General disorders    
Fatigue † 1  
# participants affected / at risk     2/13 (15.38%)  
Hunger † 1  
# participants affected / at risk     1/13 (7.69%)  
Infections and infestations    
Folliculitis † 1  
# participants affected / at risk     2/13 (15.38%)  
Pharyngitis † 1  
# participants affected / at risk     1/13 (7.69%)  
Upper respiratory tract infection † 1  
# participants affected / at risk     2/13 (15.38%)  
Anal chlamydia infection † 1  
# participants affected / at risk     1/13 (7.69%)  
Influenza † 1  
# participants affected / at risk     1/13 (7.69%)  
Oral herpes † 1  
# participants affected / at risk     1/13 (7.69%)  
Otitis externa † 1  
# participants affected / at risk     1/13 (7.69%)  
Syphilis † 1  
# participants affected / at risk     1/13 (7.69%)  
Tooth abscess † 1  
# participants affected / at risk     1/13 (7.69%)  
Injury, poisoning and procedural complications    
Procedural pain † 1  
# participants affected / at risk     1/13 (7.69%)  
Investigations    
Weight increased † 1  
# participants affected / at risk     1/13 (7.69%)  
Metabolism and nutrition disorders    
Decreased appetite † 1  
# participants affected / at risk     1/13 (7.69%)  
Musculoskeletal and connective tissue disorders    
Back pain † 1  
# participants affected / at risk     2/13 (15.38%)  
Pain in jaw † 1  
# participants affected / at risk     1/13 (7.69%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)    
Skin papilloma † 1  
# participants affected / at risk     1/13 (7.69%)  
Nervous system disorders    
Headache † 1  
# participants affected / at risk     7/13 (53.85%)  
Carpal tunnel syndrome † 1  
# participants affected / at risk     1/13 (7.69%)  
Paraesthesia † 1  
# participants affected / at risk     1/13 (7.69%)  
Psychiatric disorders    
Depression † 1  
# participants affected / at risk     1/13 (7.69%)  
Sleep disorder † 1  
# participants affected / at risk     1/13 (7.69%)  
Renal and urinary disorders    
Pollakiuria † 1  
# participants affected / at risk     1/13 (7.69%)  
Reproductive system and breast disorders    
Gynaecomastia † 1  
# participants affected / at risk     1/13 (7.69%)  
Respiratory, thoracic and mediastinal disorders    
Sinus congestion † 1  
# participants affected / at risk     2/13 (15.38%)  
Rhinitis allergic † 1  
# participants affected / at risk     1/13 (7.69%)  
Skin and subcutaneous tissue disorders    
Alopecia † 1  
# participants affected / at risk     1/13 (7.69%)  
Dermatitis † 1  
# participants affected / at risk     1/13 (7.69%)  
Eczema † 1  
# participants affected / at risk     1/13 (7.69%)  
Seborrhoeic dermatitis † 1  
# participants affected / at risk     1/13 (7.69%)  
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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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343


No publications provided by ViiV Healthcare

Publications automatically indexed to this study:

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT01499199     History of Changes
Other Study ID Numbers: 116070
Study First Received: December 15, 2011
Results First Received: August 15, 2013
Last Updated: December 5, 2013
Health Authority: United States: Food and Drug Administration