E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10020161 |
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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 |
The primary objective of the trial is to demonstrate non-inferiority in virologic response, defined as a confirmed plasma viral load of < 50 HIV-1 RNA copies/mL at Week 48 (as defined by the time ot loss of virologic response [TLOVR] algorithm), with DRV/rtv 800/100 mg q.d. versus DRV/rtv 600/100 mg b.i.d. in early ARV-experienced patients with a non-inferiority margin (delta) of 12%, when administered in combination with an individually selected OBR |
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E.2.2 | Secondary objectives of the trial |
-to evaluate safety and tolerability over 48 weeks; -to evaluate the durability of efficacy over 48 weeks; -to evaluate the change in viral load from baseline; -to evaluate the percentage subjects with a confirmed plasma viral load < 400 HIV-1 RNA copies/mL; -to evaluate the lipid effects of DRV/rtv q.d. versus b.i.d.; -to compare the immunologic response; -to evaluate resistance haracteristics; -to evaluate DRV and ritonavir pharmacokinetics following q.d. and b.i.d. dosing and explore the PK/PD relationship between: 1) DRV and efficacy/safety and 2) ritonavir and safety for b.i.d. and q.d. regimens; -to determine and compare the subject-reported Health Related Quality of Life (HRQoL) in subjects treated with DRV/rtv 800/100 mg q.d. versus DRV/rtv 600/100 b.i.d., both administered in combination with an individually selected OBR, at baseline and over 48 weeks |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Male or female subjects, aged 18 years or older. 2. Subjects with documented HIV-1 infection. 3. Stable HAART regimen for at least 12 weeks at screening. 4. In the investigators opinion, NNRTIs are not a valid treatment option, because of the subjects ARV treatment history, ARV resistance testing, medication-taking behavior, safety and tolerability concerns, or other patient-related factors. 5. Prescreening or/and screening plasma HIV-1 RNA > 1,000 copies/mL (assayed by RNA PCR standard specimen procedure) on HAART regimen at screening. 6. Screening genotype resistance test results showing none of the following mutations in the protease gene 11I, 32I, 33F, 47V, 50 V, 54L, 54M, 73S, 76V, 84V and 89V, known as DRV resistance associated mutations [RAMs]. 7. CD4+ cell count > 50 x 106 cells/mL. 8. Subjects have voluntarily signed the ICF. 9. Subjects can comply with the protocol requirements. 10. General medical condition, in the investigators opinion, does not interfere with the assessments and the completion of the trial. |
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E.4 | Principal exclusion criteria |
1. Presence of any currently active conditions that fit the definition of the WHO Clinical Stage 4, with the following exceptions: - Stable cutaneous Kaposis Sarcoma (i.e., no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the trial time period, - Wasting syndrome. 2. Current or past alcohol and/or drug use which, in the investigator's opinion, could compromise the subject's safety or adherence to the study protocol procedures. 3. Subjects for whom an investigational ARV is part of the current regimen, with the following exceptions if applicable (depending on local regulatory approval): tenofovir, emtricitabine. 4. Previous or current use of ENF, tipranavir and/or DRV. 5. Use of disallowed concomitant therapy (See Section 4.7). 6. Life expectancy of less than 12 months. 7. Pregnant or breast-feeding. 8. Female subject of childbearing potential without use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period. 9. Subjects with clinical or laboratory evidence of significantly decreased hepatic function or decompensation (i.e., liver insufficiency), irrespective of liver enzyme levels. 10. Any active clinically significant disease (e.g., tuberculosis [TB], cardiac dysfunction, pancreatitis, acute viral infections) or findings during screening of medical history or physical examination that, in the investigators opinion, would compromise the subjects safety or outcome of the trial. 11. Subjects with a grade 3 or 4 laboratory abnormality as defined by division of AIDS (DAIDS) grading tables, with the following exceptions unless clinical assessment foresees an immediate health risk to the subject: subjects with pre-existing diabetes with asymptomatic, nonfasting glucose grade 3 or 4 elevations, subjects with asymptomatic triglyceride or cholesterol elevations of grade 3 or 4. 12. Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication DRV or ritonavir. 13. Use of any non-ARV investigational agents within 60 days prior to screening without prior approval of the sponsor 14.Participation in any other investigational trial without prior approval of the sponsor |
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E.5 End points |
E.5.1 | Primary end point(s) |
Demonstration of non-inferiority in virologic response |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
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) | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | 1 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |