E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
MedDRA Classification |
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 evaluate the long-term safety and tolerability of TMC125. | |
E.2.2 | Secondary objectives of the trial | The secondary objectives are to evaluate the antiviral activity and immunological effect of TMC125 as part of an ARV regimen over time, and to evaluate genotypic and phenotypic changes over time. | |
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. Subject has signed the Informed Consent Form (ICF) voluntarily; 2. Male or female subject, aged 18 years and above; 3. Subject having previously been randomized to an active control arm of a sponsor-selected TMC125 trial and has completed the entire treatment period or has met the definition of virological failure, as defined in the original protocol, before TMC125-C211 screening or subjects who were randomized in a fully blinded TMC125 trial, being unblinded after treatment for at least 48 weeks and identified as having received placebo; 4. Subject agrees to take TMC125 in combination with the investigator-selected combination therapy consisting of at least 2 drugs (NRTIs and/or allowed PI and/or T-20; low-dose ritonavir [≤ 400 mg daily dose] is not counted as a separate ARV); 5. Subject can comply with the protocol requirements; 6. Subject’s general medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial. | |
E.4 | Principal exclusion criteria | Subjects meeting one or more of the following criteria cannot be selected: 1. Use of disallowed concomitant therapy; 2. History of or currently active alcohol or substance use which would likely compromise the subject’s safety or compliance with the study procedures; 3. Any active clinically significant disease or findings during physical examination that would compromise the subject’s safety; 4. Pregnant or breastfeeding female; 5. Female subject of childbearing potential without the use of effective birth control methods or not willing to continue practicing these birth control methods during the trial and for at least 14 days after the end of the trial (or the last intake of investigational medication): Note: Hormonal based contraception may not be reliable when taking TMC125, therefore to be eligible for this study, women of childbearing potential should either: (1) use a double barrier method to prevent pregnancy, or (2) use hormonal based contraceptives in combination with a barrier contraceptive, or (3) use an intra-uterine device in combination with a barrier contraceptive, or (4) be non-heterosexually active, practice sexual abstinence or have a vasectomized partner. Note: Women who are postmenopausal for at least 2 years, women with total hysterectomy and women who have a tubal ligation are considered of non-childbearing potential; 6. Renal impairment as defined by serum creatinine > 2 x upper limit of normal (ULN); 7. Any grade 3 or grade 4 toxicity according to the ACTG grading severity list (except for grade 3 glucose and asymptomatic triglyceride/cholesterol grade 3 or 4 elevations; or asymptomatic and isolated grade 3 or 4 elevations in gamma-glutamyl transferase [GGT] with all other liver enzymes and bilirubin within normal ranges, or isolated grade 3 elevation in amylase with no increase in lipase and no history of pancreatitis); 8. Subjects with clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels (International Normalized Ratio > 1.3 or albumin < 30 g/l or direct bilirubin > 2.5 x ULN). | |
E.5 End points |
E.5.1 | Primary end point(s) | The primary objective of the trial is to evaluate the long-term safety and tolerability of TMC125. | |
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description | |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | |
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 | Provided in protocol (part I, section 5.1.1 /page 11) | |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |