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A Pilot Study Assessing the Integrase Inhibitor GSK1349572 in HIV-infected Persons With Virus Resistant to Raltegravir

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00950859
First received: July 23, 2009
Last updated: November 5, 2015
Last verified: September 2015
Results First Received: August 15, 2013  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Infection, Human Immunodeficiency Virus
Interventions: Drug: GSK1349572 (Cohort I)
Drug: GSK1349572 (Cohort II)

  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
Participants recruited initially to Cohort I and subsequently to Cohort II. Recruitment to Cohort I was closed 9 months before recruitment to Cohort II was opened. Recruitment was not randomized.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Cohort I (DTG 50 mg OD) Participants received dolutegravir (DTG) 50 milligrams (mg) once a day (OD).
Cohort II (DTG 50 mg BID) Participants received DTG 50 mg twice a day (BID).

Participant Flow:   Overall Study
    Cohort I (DTG 50 mg OD)   Cohort II (DTG 50 mg BID)
STARTED   27   24 
COMPLETED   11   14 
NOT COMPLETED   16   10 
Adverse Event                3                3 
Insufficient Viral Load Response                12                3 
Protocol Violation                1                1 
Lost to Follow-up                0                3 



  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
Cohort I (DTG 50 mg OD) Participants received dolutegravir (DTG) 50 milligrams (mg) once a day (OD).
Cohort II (DTG 50 mg BID) Participants received DTG 50 mg twice a day (BID).
Total Total of all reporting groups

Baseline Measures
   Cohort I (DTG 50 mg OD)   Cohort II (DTG 50 mg BID)   Total 
Overall Participants Analyzed 
[Units: Participants]
 27   24   51 
Age, Customized 
[Units: Years]
Median (Full Range)
     
Years   48 
 (19 to 61) 
 47 
 (33 to 68) 
 47 
 (19 to 68) 
Gender 
[Units: Participants]
     
Female   2   6   8 
Male   25   18   43 
Race/Ethnicity, Customized 
[Units: Participants]
     
African American/African Heritage   3   5   8 
White-Arabic/North African Heritage   1   1   2 
White-White/Caucasian/European Heritage   23   18   41 


  Outcome Measures
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1.  Primary:   Number of Participants Who Achieved HIV-1 RNA <400 Copies (c)/Milliliter (mL) or at Least 0.7 log10 c/mL Below Their Baseline Value at Day 11   [ Time Frame: Baseline (Day 1) and Day 11 ]

2.  Secondary:   Mean Change From Baseline in Plasma HIV-1 RNA at Day 6 to 8, Day 11, Weeks 4, 12, 24, 48, 72, 96, From Week 108 Every 12 Weeks up to Study Completion   [ Time Frame: Baseline; Day 6 to 8; Day 11; Weeks 4, 12, 24, 48, 72, 96, from 108 every 12 weeks up to study completion ]

3.  Secondary:   Number of Participants Who Achieved Plasma HIV-1 RNA <400 c/mL and <50 c/mL at Baseline and Weeks 4, 12, 24, 48, 72, and 96: TLOVR Analysis.   [ Time Frame: Baseline; Weeks 4, 12, 24, 48, 72, and 96 ]

4.  Secondary:   Proportion of Participants Who Achieved Plasma HIV-1 RNA <400 c/mL and <50 c/mL From Week 48 Every 12 Weeks up to Study Completion   [ Time Frame: From Week 48 every 12 weeks up to study completion ]

5.  Secondary:   Change From Baseline in CD4+ Cell Count at Day 11 and Weeks 4, 12, 24, 48, 72, 96, Week 108 Every 12 Weeks up to Study Completion   [ Time Frame: Baseline; Day 11; Weeks 4, 12, 24, 48, 72, 96, from Week 108 every 12 weeks up to study completion ]

6.  Secondary:   Cmax, Cmin, and Ctau of DTG   [ Time Frame: Day 10 ]

7.  Secondary:   C0 Assessment of DTG   [ Time Frame: Day 10; Weeks 4 and 24 ]

8.  Secondary:   Tmax of DTG   [ Time Frame: Day 10 ]

9.  Secondary:   AUC0-24 Assessment of DTG   [ Time Frame: Day 10 ]

10.  Secondary:   Number of Participants With the Indicated HIV-1 Associated Conditions, Excluding Recurrences   [ Time Frame: From the day of the first dose of study drug until study completion (median 605 days for Cohort I, median 1181 days for Cohort II) ]

11.  Secondary:   Number of Participants With HIV-1 Associated Disease Progression With the Indicated Shifts to CDC Class C or Death   [ Time Frame: From the day of the first dose of study drug until study completion (median 605 days for Cohort I, median 1181 days for Cohort II) ]

12.  Secondary:   Number of Participants (Cumulative) With Protocol-defined Virological Failure (PDVF) at Day 11 and Weeks 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84, 96, Week 108 Every 12 Weeks up to Study Completion   [ Time Frame: Day 11; Weeks 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84, 96, from Week 108 every 12 weeks up to study completion ]

13.  Secondary:   Number of Participants With the Indicated Genotypic Resistance at Baseline   [ Time Frame: Baseline ]

14.  Secondary:   Median Fold Change in Sensitivity to DTG by the Baseline (Day 1) IN Mutational Group   [ Time Frame: Baseline (Day 1) ]

15.  Secondary:   Number of Participants With the Indicated Treatment-emergent Integrase (IN) Mutations Detected at the Time of Protocol-defined Virologic Failure (PDVF) as a Measure of Genotypic Resistance   [ Time Frame: From Baseline (Day 1) until study completion (median 605 days for Cohort I, median 1181 days for Cohort II) ]

16.  Secondary:   Number of Participants With the Indicated Fold Increase in DTG FC (Fold Change in IC50 Relative to Wild-type Virus) Between Baseline and the Time of PDVF, as a Measure of Post-Baseline Phenotypic Resistance   [ Time Frame: From Baseline (Day 1) until study completion (median 605 days for Cohort I, median 1181 days for Cohort II) ]

17.  Secondary:   Number of Participants With the Indicated Grade 3 and Grade 4 Clinical Chemistry Toxicities   [ Time Frame: From start of study treatment until the end of treatment visit for each participant, up to Week 264 for Cohort I and up to Week 228 for Cohort II ]

18.  Secondary:   Number of Participants With the Indicated Grade 3 and Grade 4 Hematological Toxicities   [ Time Frame: From start of study treatment until the end of treatment visit for each participant, up to Week 264 for Cohort I and up to Week 228 for Cohort II ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame SAEs, non-serious AEs and laboratory toxicities were collected from start of study treatment until the end of treatment visit for each participant, up to Week 264 for Cohort I and up to Week 228 for Cohort II.
Additional Description SAEs and non-serious AEs were collected in the Safety Population, comprised of all participants that took at least one dose of DTG.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Cohort I (DTG 50 mg OD) Participants received dolutegravir (DTG) 50 milligrams (mg) once a day (OD).
Cohort II (DTG 50 mg BID) Participants received DTG 50 mg twice a day (BID).

Other Adverse Events
    Cohort I (DTG 50 mg OD)   Cohort II (DTG 50 mg BID)
Total, other (not including serious) adverse events     
# participants affected / at risk   25/27 (92.59%)   22/24 (91.67%) 
Blood and lymphatic system disorders     
Lymphadenopathy † 1     
# participants affected / at risk   2/27 (7.41%)   4/24 (16.67%) 
Cardiac disorders     
Angina pectoris † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Ear and labyrinth disorders     
Vertigo † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Gastrointestinal disorders     
Diarrhoea † 1     
# participants affected / at risk   8/27 (29.63%)   9/24 (37.50%) 
Abdominal pain upper † 1     
# participants affected / at risk   3/27 (11.11%)   3/24 (12.50%) 
Constipation † 1     
# participants affected / at risk   3/27 (11.11%)   2/24 (8.33%) 
Gastrooesophageal reflux disease † 1     
# participants affected / at risk   3/27 (11.11%)   2/24 (8.33%) 
Nausea † 1     
# participants affected / at risk   2/27 (7.41%)   3/24 (12.50%) 
Abdominal distension † 1     
# participants affected / at risk   2/27 (7.41%)   2/24 (8.33%) 
Abdominal pain † 1     
# participants affected / at risk   4/27 (14.81%)   0/24 (0.00%) 
Vomiting † 1     
# participants affected / at risk   2/27 (7.41%)   3/24 (12.50%) 
Defaecation urgency † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Anogenital dysplasia † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
General disorders     
Pyrexia † 1     
# participants affected / at risk   3/27 (11.11%)   7/24 (29.17%) 
Asthenia † 1     
# participants affected / at risk   6/27 (22.22%)   3/24 (12.50%) 
Fatigue † 1     
# participants affected / at risk   0/27 (0.00%)   4/24 (16.67%) 
Influenza like illness † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Injection site reaction † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Oedema peripherial † 1     
# participants affected / at risk   4/27 (14.81%)   2/24 (8.33%) 
Malaise † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Immune system disorders     
Seasonal allergy † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Infections and infestations     
Bronchitis † 1     
# participants affected / at risk   6/27 (22.22%)   7/24 (29.17%) 
Rhinitis † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Sinusitis † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Upper respiratory tract infection † 1     
# participants affected / at risk   2/27 (7.41%)   5/24 (20.83%) 
Urinary tract infection † 1     
# participants affected / at risk   0/27 (0.00%)   3/24 (12.50%) 
Herpes virus infection † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Influenza † 1     
# participants affected / at risk   3/27 (11.11%)   0/24 (0.00%) 
Oral herpes † 1     
# participants affected / at risk   3/27 (11.11%)   0/24 (0.00%) 
Tooth abscess † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Nasopharyngitis † 1     
# participants affected / at risk   2/27 (7.41%)   2/24 (8.33%) 
Gastroenteritis viral † 1     
# participants affected / at risk   3/27 (11.11%)   0/24 (0.00%) 
Ear infection † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Genital herpes † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Otitis media † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Investigations     
Lipase increased † 1     
# participants affected / at risk   0/27 (0.00%)   3/24 (12.50%) 
Weight decreased † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Hypercholesterolaemia † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Vitamin D deficiency † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1     
# participants affected / at risk   5/27 (18.52%)   2/24 (8.33%) 
Myalgia † 1     
# participants affected / at risk   4/27 (14.81%)   0/24 (0.00%) 
Backpain † 1     
# participants affected / at risk   3/27 (11.11%)   3/24 (12.50%) 
Pain in extremity † 1     
# participants affected / at risk   0/27 (0.00%)   4/24 (16.67%) 
Osteoarthritis † 1     
# participants affected / at risk   3/27 (11.11%)   0/24 (0.00%) 
Muscle spasms † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Tendonitis † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Anogenital warts † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Nervous system disorders     
Headache † 1     
# participants affected / at risk   4/27 (14.81%)   3/24 (12.50%) 
Sciatica † 1     
# participants affected / at risk   2/27 (7.41%)   2/24 (8.33%) 
Dizziness † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Dysaesthesia † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Anxiety † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Psychiatric disorders     
Insomnia † 1     
# participants affected / at risk   5/27 (18.52%)   2/24 (8.33%) 
Depressed mood † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Depression † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Renal and urinary disorders     
Pollakiuria † 1     
# participants affected / at risk   0/27 (0.00%)   3/24 (12.50%) 
Respiratory, thoracic and mediastinal disorders     
Cough † 1     
# participants affected / at risk   5/27 (18.52%)   7/24 (29.17%) 
Sinus congestion † 1     
# participants affected / at risk   0/27 (0.00%)   4/24 (16.67%) 
Rhinorrhoea † 1     
# participants affected / at risk   0/27 (0.00%)   3/24 (12.50%) 
Dyspnoea † 1     
# participants affected / at risk   2/27 (7.41%)   2/24 (8.33%) 
Oropharyngeal pain † 1     
# participants affected / at risk   0/27 (0.00%)   3/24 (12.50%) 
Nasal congestion † 1     
# participants affected / at risk   0/27 (0.00%)   2/24 (8.33%) 
Skin and subcutaneous tissue disorders     
Pruritus † 1     
# participants affected / at risk   3/27 (11.11%)   0/24 (0.00%) 
Hyperhidrosis † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Intertrigo † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
Vascular disorders     
Hypertension † 1     
# participants affected / at risk   2/27 (7.41%)   0/24 (0.00%) 
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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