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 show the superiority of TMC125 compared to placebo as part of an ART containing TMC114/RTV and an investigator-selected OBR, in the proportion of subjects with undetectable plasma viral load values gt; 50copies/mL at Week 24 in treatment-experienced HIV-1 infected subjects. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are - to compare the antiviral efficacy of TMC125 to placebo in addition to the ART at all time points; - to compare the safety and tolerability of TMC125 to placebo; - to compare the immunologic changes with TMC125 to placebo; - to evaluate changes in HIV-1 genotype and drug susceptibility; - to evaluate the population pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of TMC125 and TMC114; - to evaluate and test global health status as measured by the Functional Assessment of HIV Infection FAHI questionnaire, a patient-reported outcome PRO instrument. - to collect medical resource utilization MRU information and use of a preference-based PRO instrument EuroQol-5 Dimension EQ-5D to calculate utility values, both of which may be used in future economic evaluation models. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects who meet all of the following criteria are eligible for this trial 1. Male or female subjects, aged 18 years or above. 2. Subject has signed the ICF voluntarily. 3. Subject can comply with the protocol requirements. 4. Subject with documented HIV-1 infection. 5. HIV-1 plasma viral load at screening visit above 5000 HIV-1 RNA copies/mL assayed by RNA polymerase chain reaction PCR ultrasensitive specimen procedure Roche Amplicor HIV-1 MonitorTM . 6. On a stable ART for at least 8 weeks at Screening, and willing to stay on that treatment until Baseline. 7. Documented genotypic evidence of resistance to currently available NNRTIs by having at least 1 NNRTI resistance-associated mutation present based upon the the following list, adapted from the IAS-USA 2004 A98G, L100I, K101E/P/Q, K103H/N/S/T, V106A/M, V108I, E138G/K/Q, V179I/F/G, Y181C/I/V, Y188C/H/L, G190A/E/S, P225H, F227C, M230I/L, P236L, K238N/T, Y318F 8 on the virco TYPE HIV-1 at Screening or from prior genotypic analysis, evidence of which should be available in the source documents and enrolment of the subject based on these data needs to be agreed upon by the sponsor. Note treatment with an investigational NNRTI counts as an NNRTI treatment. 8. Subject has 3 or more documented primary PI mutations as listed by the IAS-USA 2004 D30N, L33I/F, M46I/L, G48V, I50V/L, V82A/F/L/T/S, I84A/C/V, L90M 8 on the virco TYPE HIV-1 at Screening or from prior genotypic analysis, evidence of which should be available in the source documents and enrolment of the subject based on these data needs to be agreed upon by the sponsor. 9.General medical condition, in the investigator s opinion, does not interfere with the assessments and the completion of the trial. |
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E.4 | Principal exclusion criteria |
1. Primary HIV-1 infection. 2. HIV-2 infection. 3. Use of disallowed concomitant therapy 4. Any condition including but not limited to alcohol and drug use , which, in the opinion of the investigator, could compromise the subject s safety or adherence to the protocol. 5. Life expectancy less than 6 months according to the judgment of the investigator. 6. Subject has any currently active AIDS defining illness with the following exceptions, which must be discussed with the sponsor prior to enrollment Stable cutaneous Kaposi s Sarcoma i.e., no pulmonary or gastrointestinal involvement other than oral lesions that is unlikely to require any form of systemic therapy during the trial period. Wasting syndrome due to HIV infection. 7. Any active clinically significant disease e.g., pancreatitis, cardiac dysfunction or findings during screening of medical history or physical examination that, in the investigator s opinion, would compromise the outcome of the trial. 8. Acute viral hepatitis including but not limited to A, B, or C. 9. Chronic hepatitis B and/or C with aspartate aminotransferase AST and/or alanine aminotransferase ALT lt; 5 x upper limit of normal ULN . 10. Receipt of an investigational drug within 30 days prior to the trial drug administration, with the exceptions of TMC114 and tipranavir, tenofovir, emitricitabine, or Truvada where these are not yet licensed in a participating country. 11. Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medications administered in this trial. 12. Pregnant or breastfeeding female subject. 13. Female subject of childbearing potential not using effective birth control methods or not willing to continue practicing these birth control methods during the trial and for at least 30 days after the end of the trial or after last intake of investigational ARVs ; 14. Heterosexually active male subject not using effective birth control methods or not willing to continue practicing these birth control methods during the trial and until 30 days after the end of the trial or after last intake of investigational ARVs . 15. Any grade 3 or grade 4 toxicity according to the Division of AIDS DAIDS grading scale, 16. Subject with clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels International Normalized Ratio INR lt; 1.5 or albumin gt; 30 g/L or bilirubin lt; 2.5 x ULN . 17. Subjects who previously received treatment with either TMC125, TMC120, or TMC278 in a previous clinical trial. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The superiority of TMC125 over placebo, with respect to proportion of subjects with undetectable plasma viral load values gt;50 copies/mL calculated according to the TLOVR algorithm at week 24. |
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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 | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 8 |