HIV-1 infection MedDRA version: 9.1 Level: LLT Classification code 10020192 Term: HIV-1
Conditions
Interventions
Trade Name: Intelence 100 mg tablets
Product Name: etravirine (ETR, TMC125)
Product Code: TMC125 (R165335) F060
Pharmaceutical Form: Tablet
INN or Proposed INN: etravirine
CAS Number: 269055-15-4
Curr
Sponsors
Tibotec Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects, aged 18 years or above. 2. Subject has signed the informed consent form (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 500 HIV-1 RNA copies/mL. 6. Subject has received at least one HAART regimen Note: HAART is defined as potent anti-HIV treatment usually including a combination of 3 or more drugs with activity against HIV whose purpose is to reduce viral load to undetectable. This regimen usually includes treatment with at least 2 NRTIs in combination with at least 1 additional ARV from the NNRTI and/or PI class. Note: Subjects on a structured treatment interruption for a minimum of 4 weeks at the time of screening are allowed. 7. On a stable antiretroviral therapy (ART) for at least 8 weeks at Screening and willing to stay on that treatment until the start of the Pre-Treatment Phase. 8. Presence of at least 1 of the following mutations (based upon the following list of 47 NNRTI RAMs: V90I, A98G, L100I, K101E/H/P/Q, K103H/N/S/T, V106A/I/M, V108I, E138A/G/K/Q, V179D/E/F/G/I/T, Y181C/I/V, Y188C/H/L, V189I, G190A/C/E/Q/S, H221Y, P225H, F227C/L, M230I/L, P236L, K238N/T, Y318F) on the resistance test at Screening or from prior genotypic analysis, evidence of which should be available in the source documents and enrollment of the subject based on these data needs to be agreed upon by the sponsor. 9. Demonstrated sensitivity to ATV, ETR and at least one of the selected NRTIs based on the resistance test at Screening. 10.General medical condition, in the investigator’s opinion, does not interfere with the assessments and completion of the trial. Subjects who meet all of the criteria above and the following criteria are eligible for the substudy: 1. Currently enrolled in trial TMC125-C238 for > 24 weeks. 2. Informed Consent Form (ICF) signed voluntarily. 3. HIV-1 plasma viral load =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Primary HIV-1 infection. 2. Previously documented HIV-2 infection. 3. Previously failed 2 or more HIV PI-containing regimens. 4. Use of disallowed concomitant therapy. 5. Previous diagnosis of hereditary hyperbilirubinemia (eg. Gilbert’s syndrome, Crigler- Najjar syndrome). 6. 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. 7. Life expectancy less than 6 months according to the judgment of the investigator. 8. Subject has any currently active AIDS defining illness with the following exceptions, which must be discussed with the sponsor prior to enrollment: a. 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. b. Wasting syndrome due to HIV infection if, in the investigator’s opinion, it is not actively progressive and its treatment does not require hospitalization or compromise the subject’s safety or compliance to adhere to trial related procedures. Note: An AIDS defining illness not clinically stabilized for at least 30 days will be considered clinically active. Primary and secondary prophylaxis for an AIDS defining illness is allowed in case the medication used is not part of the disallowed medication. 9. Any active clinically significant disease (e.g., pancreatitis, cardiac dysfunction) or findings during screening of medical history, laboratory or physical examination that, in the investigator’s opinion, would compromise the subject’s safety or outcome of the trial. 10. Acute viral hepatitis including but not limited to A, B, or C. 11. Chronic hepatitis B and/or C co-infection. 12. Receipt of an investigational drug or investigational vaccine within 30 days prior to the trial drug administration. 13. Previously demonstrated clinically significant allergy or hypersensitivity to ETR or to any of the excipients of ETR. 14. Pregnant or breastfeeding female subject. 15. 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 medication; Note: Hormone-based contraception may not be reliable when taking ARV agents; therefore, to be eligible for this trial, women of childbearing potential should either: • use a double barrier method to prevent pregnancy (i.e., using a male condom with diaphragm or cervical cap); or • use an hormonal contraceptive in combination with a barrier contraceptive (i.e., female/male condom, diaphragm or cervical cap); or • use an intrauterine device (IUD) in combination with a barrier contraceptive (i.e., female/male condom, diaphragm or cervical cap); or • do not engage in heterosexual sex, or have a vasectomized partner with confirmed sterility. Note: Women who are postmenopausal for at least 2 years and women with surgical sterilization, i.e., tubal ligation or total hysterectomy, are considered of non-childbearing potential. Note: Spermicides contain non-oxynol-9 and 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. 16. Non-vasectomized heterosexually active male subject not using effective birth control methods or no
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •to evaluate the pharmacokinetic interaction between ETR and ATV/rtv at 2 different doses;Secondary Objective: •to assess the impact of cytochrome P450 (CYP) 2C9 and 2C19 genotypes on ETR pharmacokinetics; • to evaluate safety and tolerability of ETR in combination with ATV/rtv and 1 NRTI over 48 weeks; • to evaluate the antiviral activity of ETR in combination with ATV/rtv and 1 NRTI over 48 Weeks; • to evaluate the immunologic changes (as measured by CD4 cells) with ETR and ATV/rtv with 1 NRTI over 48 weeks; • to evaluate changes in viral genotype and drug susceptibility over 48 weeks.;Primary end point(s): The first analysis will be performed when all subject have been treated with ETR for 12 weeks or discontinued earlier. The purpose of this analysis is mainly to evaluate the pharmacokinetics, safety, and short-term antiviral responses. | — |
Countries
France
Outcome results
None listed