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: 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
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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.
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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 ]

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
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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 96+ follow-up visit (if applicable).
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 (100.00%) 
Blood and lymphatic system disorders   
Anaemia † 1   
# participants affected / at risk   1/13 (7.69%) 
Increased tendency to bruise † 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   4/13 (30.77%) 
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   2/13 (15.38%) 
Gastrooesophageal reflux disease † 1   
# participants affected / at risk   1/13 (7.69%) 
Haemorrhoids † 1   
# participants affected / at risk   3/13 (23.08%) 
General disorders   
Fatigue † 1   
# participants affected / at risk   3/13 (23.08%) 
Hunger † 1   
# participants affected / at risk   1/13 (7.69%) 
Impaired healing † 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   2/13 (15.38%) 
Upper respiratory tract infection † 1   
# participants affected / at risk   5/13 (38.46%) 
Anal chlamydia infection † 1   
# participants affected / at risk   1/13 (7.69%) 
Influenza † 1   
# participants affected / at risk   2/13 (15.38%) 
Oral herpes † 1   
# participants affected / at risk   2/13 (15.38%) 
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%) 
Acarodermatitis † 1   
# participants affected / at risk   2/13 (15.38%) 
Conjunctivitis † 1   
# participants affected / at risk   2/13 (15.38%) 
Herpes simplex † 1   
# participants affected / at risk   2/13 (15.38%) 
Oropharyngeal gonococcal infection † 1   
# participants affected / at risk   2/13 (15.38%) 
Body tinea † 1   
# participants affected / at risk   1/13 (7.69%) 
Bronchitis † 1   
# participants affected / at risk   1/13 (7.69%) 
Chlamydial infection † 1   
# participants affected / at risk   1/13 (7.69%) 
Gonorrhoea † 1   
# participants affected / at risk   1/13 (7.69%) 
Otitis media † 1   
# participants affected / at risk   1/13 (7.69%) 
Sinusitis † 1   
# participants affected / at risk   1/13 (7.69%) 
Injury, poisoning and procedural complications   
Procedural pain † 1   
# participants affected / at risk   3/13 (23.08%) 
Excoriation † 1   
# participants affected / at risk   1/13 (7.69%) 
Investigations   
Weight increased † 1   
# participants affected / at risk   1/13 (7.69%) 
Lipase 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%) 
Hyperlipidaemia † 1   
# participants affected / at risk   1/13 (7.69%) 
Musculoskeletal and connective tissue disorders   
Back pain † 1   
# participants affected / at risk   1/13 (7.69%) 
Pain in jaw † 1   
# participants affected / at risk   1/13 (7.69%) 
Musculoskeletal pain † 1   
# participants affected / at risk   3/13 (23.08%) 
Myalgia † 1   
# participants affected / at risk   1/13 (7.69%) 
Myositis † 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%) 
Sciatica † 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%) 
Emotional disorder † 1   
# participants affected / at risk   1/13 (7.69%) 
Insomnia † 1   
# participants affected / at risk   1/13 (7.69%) 
Libido decreased † 1   
# participants affected / at risk   1/13 (7.69%) 
Renal and urinary disorders   
Pollakiuria † 1   
# participants affected / at risk   1/13 (7.69%) 
Urine flow decreased † 1   
# participants affected / at risk   1/13 (7.69%) 
Reproductive system and breast disorders   
Gynaecomastia † 1   
# participants affected / at risk   1/13 (7.69%) 
Prostatitis † 1   
# participants affected / at risk   2/13 (15.38%) 
Respiratory, thoracic and mediastinal disorders   
Sinus congestion † 1   
# participants affected / at risk   2/13 (15.38%) 
Rhinitis allergic † 1   
# participants affected / at risk   3/13 (23.08%) 
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%) 
Rash † 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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