E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HIV-1 infected antiretroviral therapy naïve adult subjects |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008922 |
E.1.2 | Term | Chronic infection with HIV |
|
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 select a GSK1349572 once daily dose for further evaluation in Phase III based on a comparison of the Week 16 antiviral activity and tolerability of a range of oral doses of GSK1349572 in HIV-1 infected therapy-naïve adult subjects. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effect of various GSK1349572 doses on selected virological and immunological markers of HIV infection through Week 16 To evaluate the safety and tolerability of GSK1349572 doses through Week 16 To characterize the PK parameters of GSK1349572 using intensive and sparse PK sampling strategies and to explore exposure-response relationships To confirm the Week 16 GSK1349572 once daily selected dose at Week 24 based on antiviral activity in conjunction with immunologic, safety and PK measures To assess the development of viral resistance to GSK1349572 and other on-study ARTs in subjects experiencing virological failure To evaluate the effect of various demographic factors on exposure-response parameters of GSK1349572 To assess the HIV-1 RNA decay rate over the initial 2 weeks of treatment To evaluate the antiviral activity, safety, tolerability and development of viral resistance of the selected dose of GSK1349572 relative to EFV over time
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. HIV-1 infected males or females of non-childbearing potential ≥ 18 years of age. For the purposes of this trial, a woman is considered of non-childbearing potential if she is physiologically incapable of becoming pregnant. This includes pre-menopausal females with a documented tubal ligation, hysterectomy or bilateral oophorectomy or post-menopausal women (defined as 12 months of spontaneous amenorrhea) 2. HIV-1 infection with a screening plasma HIV-1 RNA ≥1000 c/mL 3. CD4+ cell count ≥100 cells/mm3 (or higher as local guidelines dictate) 4. ART-naive defined as having <10 days of prior therapy with any antiretroviral agent. Any previous exposure to an HIV integrase inhibitor other than GSK1349572 will be exclusionary. 5. Subject has no evidence of genotypic or phenotypic viral resistance to any antiretroviral drug indicative of primary transmitted resistance in screening genotype or phenotype or historical resistance test result 6. Able to understand and comply with protocol requirements, instructions, and protocol-stated restrictions and is likely to complete the study as planned 7. Signed and dated written informed consent is obtained from the subject or the subject’s legal representative prior to screening. 8. French subjects: 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.
|
|
E.4 | Principal exclusion criteria |
1. Any pre-existing mental, physical, or substance abuse disorder which may interfere with the subject’s ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the subject 2. Women of childbearing potential, pregnant women or women who are breastfeeding 3. Any evidence of an active CDC Category C disease except cutaneous Kaposi’s sarcoma not requiring systemic therapy at the screening visit. 4. Previous participation in an experimental drug and/or vaccine trials (s) within 30 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer 5. History of ongoing or clinically relevant pancreatitis or hepatitis within the previous 6 months, including chronic HBV infection. 6. Serious medical condition which would compromise the safety of the subject 7. Any condition which may interfere with the ADME of the drug or render the subject unable to take oral medication. 8. Any acute laboratory abnormality at screening, which would preclude the subject’s participation in the study of an investigational compound. 9. Subject has estimated creatinine clearance <50 mL/min 10. ALT ≥5 times ULN. Subjects with ALT > 2xULN but <5xULN may participate in the study if the abnormality will not interfere with the study procedures or compromise subject safety 11. Screening ALT ≥3xULN and bilirubin ≥1.5xULN 12. History or presence of allergy or intolerance to the study drugs or drugs of their class, or a history of drug or other allergy that contraindicates participation. 12. Treatment with radiation therapy or cytotoxic chemotherapeutic agents within 28 days prior to screening, or has an anticipated need during the study 13. Required treatment with immunomodulators within 28 days or subject has received an HIV-1 immunotherapeutic vaccine within 90 days 14. Treatment with foscarnet, hydroxyurea or other agents with documented activity against HIV-1 in vitro within 28 days of study administration 15. History of cardiovascular risk factors including clinically significant cardiac disease 16. Personal or family history of prolonged QT syndrome 17. Any clinically significant finding on screening or baseline ECG18. Significant blood loss within a 56 day period 19. Immunization within 30 days 20. French subjects: The subject has participated in any study using an investigational drug 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of subjects with HIV-1 RNA <50 c/ml through Week 16 using the TLOVR algorithm. Dose selection will be based primarily on antiviral activity and tolerability in conjunction with immunologic, safety and PK measures will also be considered. |
|
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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
|
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
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 | 5 |
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 |