A Phase III randomized, double-blinded, placebo-controlled trial to investigate the efficacy, tolerability and safety of TMC125 as part of an ART including TMC114/RTV and an investigator-selected OBR in HIV-1 infected subjects with limited to no treatment options.A substudy of TMC125-C216 to evaluate the pharmacokinetic profile of TMC125, TMC114 and RTV at Week 4 and 24, coadministered with an individually optimized antiretroviral therapy.(v 1.0, 20 July 2005)
- Conditions
- HIV-1 infection
- Registration Number
- EUCTR2005-003160-32-ES
- Lead Sponsor
- Tibotec Pharmaceuticals Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 600
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) 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.
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
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 infections, including HIV.
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 DAIDS grading scale, except for: grade 3 glucose elevation, asymptomatic grade
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method