| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HIV-1 infected antiretroviral therapy naive adult subjects. |
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| E.1.1.1 | Medical condition in easily understood language |
| HIV-1 infected antiretroviral therapy naive adult subjects. |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 14.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10008922 |
| E.1.2 | Term | Chronic infection with HIV |
| E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 plus ABC/3TC FDC once daily therapy compared to Atripla over 48 weeks in HIV-1 infected ART-naïve subjects. |
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| E.2.2 | Secondary objectives of the trial |
• To demonstrate the antiviral activity of the GSK1349572 plus ABC/3TC FDC once daily therapy compared to Atripla over 96 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
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|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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 <1% per year (not all IUDs meet this criterion, see the SPM for an example listing of approved IUDs).
• Any other method with published data showing that the expected failure rate is <1% per year.
• Hormonal contraception plus a barrier method. Hormonal contraception alone will not be considered adequate for inclusion into or participation in this study (due to potential receipt of blinded efavirenz in this trial).
3. HIV-1 infection as documented by Screening plasma HIV-1 RNA 1000 c/mL;
4. Antiretroviral-naive ( 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection).
5. A negative HLA-B*5701 allele screening assessment.
6. Signed and dated written informed consent is obtained from the subject or the subject’s legal representative prior to screening.
7. 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.
8. Subject is able to understand and comply with protocol requirements, instructions, and protocol-stated restrictions and is likely to complete the study as planned.
9. Subject must be considered appropriate candidates for participation in an investigative clinical trial with oral medication e.g. no active substance abuse, acute major organ disease.
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|
| E.4 | Principal 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.
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| E.5 End points |
| E.5.1 | 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. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
| 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 |
| Randomized, stratified, double-blind, double-dummy, active-controlled, multicenter, parallel group |
|
| 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.8.2.3.1 | Comparator description |
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| E.8.2.4 | Number of treatment arms in the trial | 2 |
| 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 68 |
| 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 | Yes |
| 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 | 4 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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