A Phase II, randomized, active controlled, open label trial to investigate the efficacy and tolerability of TMC125 in HIV-1 infected subjects, who are PI-naïve and with documented genotypic evidence of NNRTI resistance from previous NNRTI use.A sub-study of TMC125-C227 to evaluate the pharmacokinetic profile at baseline and at week 4 of TMC125 800 mg b.i.d. administered in addition to 2 investigator-selected NRTIs. (version 2.0, 26 October 2004)
- Conditions
- HIV-1 infection
- Registration Number
- EUCTR2004-001657-29-ES
- Lead Sponsor
- Tibotec Pharmaceuticals Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 120
1. Voluntarily signed informed consent;
2. Documented HIV-1 infection;
3. Male or female subjects, aged above 18 years;
4. Subject can comply with the protocol requirements;
5. Subject:
- is currently on a treatment interruption (minimum duration of 4 weeks) at screening and agreeing to remain without ART until baseline
OR
- is currently receiving a stable (minimum duration of 12 weeks) NNRTI-containing ART at screening and agreeing to stay on that ART until baseline
Note: These subjects must be virologically-failing on this first-line NNRTI-containing regimen as documented by a detectable HIV-1 plasma viral load measurement tested locally, prior to and consecutive with the screening sample;
OR
- has been treated with an NNRTI, either alone or with other ARVs, for prevention of MTCT
Note: Subjects treated with an NNRTI-containing regimen for prevention of MTCT are allowed in the trial, however, this subject population will be limited to 25% of the total number of subjects;
6. HIV-1 plasma viral load at screening visit is greater than 1000 HIV-1 RNA copies/mL [assayed by RNA polymerase chain reaction (PCR) ultrasensitive specimen procedure, Roche Amplicor HIV-1 MonitorTM (version 1.5)];
7. NNRTI-experienced with documented genotypic evidence of resistance to currently available NNRTIs either present at screening or from prior genotypic analysis available in the source documents and after agreement with the sponsor to enroll the subject based on these historical data. A minimum of 1 of the following NNRTI- associated mutations should be present based on the IAS-USA Drug Resistance Mutation Guidelines.
A98G L100I K101E K101P K101Q K103H
K103N K103S K103T V106A V106M V108I
Y181C Y181I Y181V Y188C Y188H Y188L
G190A G190E G190S P225H M230L P236L
K238N K238T Y318F
8. Subject should be naïve and sensitive on the virco®TYPE HIV-1 for the 2 NRTIs to be used in the underlying ART.
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
1. Previous treatment with PIs;
2. Previous treatment with a regimen containing only NRTIs. Subjects may have been treated with NRTIs for the prevention of MTCT;
3. Use of disallowed concomitant therapy during the 14 days prior to the start of the treatment period;
4. History of, or currently active, alcohol or drug use that in the investigator’s opinion would likely compromise the subject’s safety and/or compliance with the trial procedures;
5. Life expectancy less than 6 months;
6. Subject currently having any active AIDS defining illness with the following exceptions:
- Stable, cutaneous Kaposi’s Sarcoma that is considered at screening unlikely to require any form of systemic therapy during the trial period;
-Wasting syndrome due to HIV infection if, it is not actively progressive and its treatment does not require hospitalization or compromise the subject’s safety or ability to adhere to the trial protocol procedures. If subjects are on maintenance therapy for previously diagnosed wasting, they may be eligible for the trial only if such treatment is not included in the list of disallowed medications.
7. Any active clinically significant disease or findings during screening of medical history or physical examination that would compromise the outcome of the trial;
8. Receipt of any investigational drug within 30 days prior to the trial drug administration (except for tenofovir and emtricitabine, which are allowed);
9. Previous permanent discontinuation of any NNRTI due to cutaneous events;
10.Previously demonstrated clinically significant allergy or hypersensitivity to any of the components of the investigational medication;
11.Pregnant or breastfeeding female;
12.Female 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 after last intake of ART). Note: Hormonal based contraception may not be reliable when taking TMC125, 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 hormonal based contraceptives in combination with a barrier contraceptive OR
iii. Use an intrauterine device (IUD) in combination with a barrier contraceptive OR
iv. Be non-heterosexually active, practice sexual abstinence, or have a vasectomized partner.
Note: women who are post-menopausal for at least 2 years, women with total hysterectomy and women who have had a tubal ligation are considered of non-childbearing potential.
13. Renal impairment as defined by serum creatinine > 2 x the upper limit of normal (ULN);
14. Any grade 3 or grade 4 toxicity according to the ACTG grading severity list [except for grade 3 glucose, asymptomatic triglyceride/cholesterol grade 3 or 4 elevations, isolated grade 3 increases in gamma-glutamyl transferase (GGT) or isolated grade 3 increases in amylase with no increase in lipase and no history of pancreatitis];
15.Acute hepatitis A, B or C;
16.Chronic hepatitis B or C with aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 x ULN;
17.Subjects with clinical or laboratory evidence of significantly decreased hepatic function or decompensation, irrespective of liver enzyme levels [e.g., International Normalized Ratio (INR) > 1.3 or albumin < 30 g/l or bilirubin > 2.5 x ULN]
18.Subjects who have been randomized to a TMC125 and/or TMC120 and/or R278474 tr
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