E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-1 infected antiretroviral (ART) - naïve adult subjects |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008922 |
E.1.2 | Term | Chronic infection with HIV |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate the antiviral activity of GSK1349572 50 mg administered once daily compared to RAL 400 mg twice daily over 48 weeks in HIV-1 infected therapy naïve subjects. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate the antiviral activity of GSK1349572 compared to RAL over 96 weeks. To compare the tolerability, long-term safety and antiviral and immunologic activity of GSK1349572 to RAL over time. To assess the development of viral resistance in subjects experiencing virological failure. To characterize the pharmacokinetics (PK) of GSK1349572 using a sparse PK sampling strategy and a population modelling approach. To explore exposure-response relationships of GSK1349572. To evaluate the effect of patient characteristics and concurrent medications on PK parameters of GSK1349572. To evaluate the incidence of HIV-associated conditions in subjects treated with GSK1349572 compared to RAL over time. To explore the impact of gender, race and/or HIV-1 subtype on response GSK1349572 and RAL over time. To explore the change in utility and health related quality of life for subjects treated with GSK1349572 and RAL.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Eligible subjects must •be able to understand and comply with protocol requirements, instructions, and restrictions. •be likely to complete the study as planned. •be considered appropriate candidates for participation in an investigative clinical trial with oral medication (e.g., no active substance abuse, acute major organ disease). Laboratory results from the central laboratory services provided by this trial will be used to assess eligibility. If results from the central laboratory (e.g., genotype results) will delay screening beyond the defined 28-day period, use of local laboratory results may be used only after consultation and agreement with GSK. Subjects eligible for enrolment in this study must meet all of the following 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). •Approved hormonal contraception (see the SPM for a listing of examples of approved hormonal contraception). •Any intrauterine device (IUD) with published data showing that the expected failure rate is <1% per year (not all IUDs meet this criterion, see the SPM for a listing of example approved IUDs). •Any other method with published data showing that the expected failure rate is <1% per year. Any contraception method must be used consistently and in accordance with the approved product label. All subjects participating in the study should be counselled on safer sexual practices including the use of effective barrier methods (e.g., male condom/spermicide). 3.HIV-1 infection as documented by Screening plasma HIV-1 RNA >1000 c/mL; 4.Antiretroviral-naïve (< 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection). 5.Signed and dated written informed consent is obtained from the subject or the subject’s legal representative prior to screening. 6.For subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Note: subjects starting abacavir as part of the NRTI backbone must be or have been screened and be negative for the HLA-B*5701 allele.
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria must not be enrolled in the study: Exclusionary medical conditions 1.Women who are breastfeeding; 2.Any evidence of an active Center for Disease and Prevention Control (CDC) Category C disease [CDC, 1992], except cutaneous Kaposi’s sarcoma not requiring systemic therapy or historic or current CD4+ cell levels <200cells/mm3; 3.Subjects with moderate to severe hepatic impairment as determined by Child-Pugh classification (see Appendix 1); 4.Anticipated need for HCV therapy during the study; 5.History or presence of allergy or intolerance to the study drugs or their components or drugs of their class; 6.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 GSK medical monitor for inclusion of the subject; Exclusionary Treatments prior to Screening or Day 1 7.Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening; 8.Treatment with any of the following agents within 28 days of Screening; • radiation therapy; • cytotoxic chemotherapeutic agents; • any immunomodulator; 9.Treatment with any agent, except recognized ART as allowed above (Section 4.2), with documented activity against HIV-1 in vitro within 28 days of first dose of IP; 10.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; 11.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 the subject will participate simultaneously in another clinical study; Exclusionary Lab Values or Clinical Assessments at Screening 12.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; 13.Any verified Grade 4 laboratory abnormality (a single repeat test is allowed during the Screening period to verify a result). 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; 14.Alanine aminotransferase (ALT) >5 times the upper limit of normal (ULN); 15.ALT > 3xULN and bilirubin > 1.5xULN (with >35% direct bilirubin); 16.Subject has estimated creatinine clearance <50 mL/min via Cockroft-Gault method; 17.Recent history (<3 months) of any upper or lower gastrointestinal bleed, with the exception of anal or rectal bleeding. 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for this study will be the proportion of subjects with HIV-1 RNA <50 c/mL through Week 48 using a Missing, Switch or Discontinuation = Failure (MSDF) algorithm as codified by the FDA’s “snapshot” algorithm. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
96 week randomised phase followed by open label phase |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |