HIV-1 infection MedDRA version: 9.0 Level: LLT Classification code 10020192
Conditions
Interventions
Product Name: TMC114 ethanolate
Product Code: TMC114
Pharmaceutical Form: Tablet
CAS Number: 206361-99-1
Current Sponsor code: TMC114
Sponsors
Tibotec Pharmaceuticals Limited
Eligibility
Sex/Gender
All
Inclusion criteria
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 following list, adapted from the IAS-USA: 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) 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. 8. Subject has 3 or more documented primary PI mutations (as listed by the most recent IAS-USA list of mutations; currently the list of November 2005 (see addendum 9) which will be updated according to any new published list) on the virco®TYPE HIV-1 at Screening. 9. General medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting 1 or more of the following criteria cannot be selected. 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 that is unlikely to require any form of systemic therapy during the trial period. · Wasting syndrome due to HIV infection. Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed in case the medication used is not part of the disallowed medication. 7. Any active clinically significant disease 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) > 5 x upper limit of normal (ULN). Note: Subjects co-infected with chronic hepatitis B or C will be allowed to enter the trial if their condition is clinically stable and is not expected to require treatment during the trial period.. 10. Receipt of an investigational drug within 30 days prior to the trial drug administration, with the exceptions of TMC114 and tipranavir, tenofovir, emitracitabine, or TruvadaÒ 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). Note: Hormone-based contraception may not be reliable when taking investigational agents; therefore, to be eligible for this trial, women of childbearing potential should either: (i) use a double barrier method to prevent pregnancy OR (ii) use hormone-based contraceptive in combination with a barrier contraceptive OR (iii) use an intrauterine device (IUD) in combination with a barrier contraceptive OR (iv) do not engage in heterosexual sex, or have a vasectomized partner with confirmed sterility. Note: Women who are postmenopausal for at least 2 years, women with total hysterectomy, and women who have a tubal ligation are considered of nonchildbearing potential. Note: Spermacides containing non-oxynol-9 should not be used as this can potentially increase the rate of HIV-1 transmission. Note: Use of an IUD can increase the risk of sexually transmitted inf
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 (< 50copies/mL) at Week 24 in treatment-experienced HIV-1 infected subjects.; Secondary Objective: - 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 instrument. - to collect medical resource utilization (MRU) information and use of a preference-based PRO instrument (EuroQol-5 Dimension) to calculate utility values, both of which may be used in future economic evaluation models. The objective of the pharmacokinetic substudy is to obtain full pharmacokinetic profiles of TMC125, TMC114 and RTV, after 4 and 24 weeks of treatment when given together as part of an ART. ; Primary end point(s): The primary objective is to show superiority of TMC125 over placebo, with respect to proportion of subjects with undetectable plasma viral load values (<50 copies/mL) calculated according to the TLOVR algorithm at Week 24. | — |
Countries
Germany, United Kingdom
Outcome results
None listed