HIV-1 infected antiretroviral therapy naive adult subjects. MedDRA version: 14.1 Level: LLT Classification code 10008922 Term: Chronic infection with HIV System Organ Class: 100000004862
Conditions
Interventions
Product Code: GSK1349572
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: dolutegravir
CAS Number: 1051375-19-9
Current Sponsor code: GSK1349572
Concentration unit: mg milligram(s)
Concen
Sponsors
ViiV Healthcare UK Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. HIV-1 infected adults =18 years of age. 2. A female, may be eligible to enter and participate in the study if she: a. is of non-child-bearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea and = 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy or, b. is of child-bearing potential with a negative pregnancy test at both Screening and Day 1 and agrees to use one of the following methods of contraception to avoid pregnancy. • Complete abstinence from intercourse from 2 weeks prior to administration of IP, throughout the study, and for at least 2 weeks after discontinuation of all study medications. • Double barrier method (male condom/spermicide, male condom/diaphragm, diaphragm/spermicide). • Any intrauterine device (IUD) with published data showing that the expected failure rate is =65 years) yes F.1.3.1 Number of subjects for this age range 7
Exclusion criteria
Exclusion criteria: 1. Women who are breastfeeding. 2. Any evidence of an active Center for Disease Control and Prevention (CDC) Category C disease [CDC, 1992], except cutaneous Kaposi’s sarcoma not requiring systemic therapy. Subjects may be enrolled provided they are on stable, anti-infective treatment or profhylaxis regimen and are clinically improving on baseline visit (Historical or current CD4 cell counts less than 200cells/mm3 are not exclusionary). 3. Subjects with any degree of hepatic impairment. 4. Positive for Hepatitis B at screening (+HbsAg), or anticipated need for HCV therapy during the study. 5. Recent history (=3 months) of any upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding. 6. History or presence of allergy or intolerance to the study drugs or their components or drugs of their class. 7. History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma; other localized malignancies require agreement between the investigator and Study medical monitor for inclusion of the subject. Exclusionary Treatments prior to Screening or Day 1 8. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening; 9. Treatment with any of the following agents within 28 days of Screening i. radiation therapy ii. cytotoxic chemotherapeutic agents iii. any immunomodulator 10. Treatment with any agent, except recognized ART as allowed within inclusion criteria, with documented activity against HIV-1 in vitro within 28 days of first dose of investigational product (IP). Allowed ART cannot be given within 28 days of first dose. 11. Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of IP. 12. French subjects recruited at sites in France will be excluded if the subject has participated in any study using an investigational agent during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening for the study or if the subject will participate simultaneously in another clinical study. Exclusionary Laboratory or Clinical Assessments at Screening 13. Any evidence of primary viral resistance in the Screening result or, if known, any historical resistance test result. Note: retests of Screening genotypes are not allowed. 14. Any verified Grade 4 laboratory abnormality (a single repeat test is allowed during the Screening period); Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject’s participation in the study of an investigational compound is exclusionary. 15. Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN). 16. ALT =3xULN and bilirubin =1.5xULN (with >35% direct bilirubin). 17. Subject has creatinine clearance of <50mL/min via Cockroft-Gault method. Notwithstanding these minimum inclusion and exclusion criteria, Investigators must also follow country specific guidelines where they exist when making decisions about subjects who are eligible for study participation.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the antiviral activity of GSK1349572 plus ABC/3TC FDC once daily therapy compared to Atripla over 48 weeks in HIV-1 infected ART-naïve subjects.;Secondary Objective: •To demonstrate the antiviral activity of the GSK1349572 plus ABC/3TC FDC once daily therapy compared to Atripla over 96 weeks; and up to 144 weeks; •To compare the tolerability, long-term safety and antiviral and immunologic activity of GSK1349572 plus ABC/3TC FDC once daily therapy to Atripla over time; •To assess the development of viral resistance in subjects experiencing virological failure; •To assess the change in symptom bother count for subjects treated with GSK1349572 plus ABC/3TC FDC once daily therapy and Atripla •To evaluate the incidence of HIV-associated conditions in subjects treated with GSK1349572 plus ABC/3TC FDC once daily therapy compared to Atripla over time •To explore the impact of gender, race, and/or HIV-1 subtype on response to GSK1349572 plus ABC/3TC FDC once daily therapy and Atripla over time •To explore the change in utility and health related quality of life for subjects treated with GSK1349572 plus ABC/3TC FDC once daily therapy and Atripla ;Primary end point(s): Proportion of subjects with plasma HIV-1 RNA <50 copies/mL through Week 48 using the Missing, Switch, or Discontinuation = Failure (MSDF) algorithm as codified by the FDA’s “snapshot” algorithm - details within Protocol. ;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy endpoints • Time to viral suppression (<50 copies/mL) • Proportion of subjects with plasma HIV-1 RNA <50 copies/mL at Week 96 and Week 144 • Change from baseline in CD4+ cells at week 48 • Proportion of subjects with HIV-1 RNA =1,000 copies/mL at or after 16 and before 24 weeks, or ? 200 copies/mL at 24 weeks [Sax, 2009] • Symptom distress module: change in overall symptom bother count from baseline to Week 4 • Absolute values and change from Baseline in plasma HIV-1 RNA over time • Absolute values and changes from Baseline in CD4+ and CD8+ cell counts over time • Incidence of disease progression (HIV-associated conditions, AIDS and death) Safety endpoints • Incidence and severity of AEs and laboratory abnormalities • Absolute values and changes over time in laboratory parameters • Proportion of subjects who discontinue treatment due to AEs • Incidence of any clinically significant changes in electrocardiograph (ECG) profiles • Change from Baseline in vital signs ;Timepoint(s) of evaluation of this end point: Over 144 weeks or as specified | — |
Countries
Australia, Belgium, Canada, Denmark, France, Germany, Hungary, Italy, Netherlands, Poland, Romania, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials HelpDesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed