HIV-1 MedDRA version: 9.1 Level: LLT Classification code 10020161 Term: HIV infection
Conditions
Interventions
Product Name: TMC114 ethanolate
Product Code: TMC114
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: darunavir
CAS Number: 206361-99-1
Current Sponsor code: TMC114 (F032)
Other descriptiv
Sponsors
Tibotec Pharmaceuticals Ltd.
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 older. 2. Subjects with documented HIV-1 infection. 3. Stable HAART regimen for at least 12 weeks at screening. 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 PIs classes or a combination of 3 NRTIs. 4. In the investigator’s opinion, NNRTIs are not a valid treatment option, because of the subject’s ARV treatment history, ARV resistance testing, medication-taking behavior, safety and tolerance concerns, or other patient-related factors. 5. Prescreening or/and screening plasma HIV-1 RNA > 1,000 copies/mL (assayed by RNA PCR standard specimen procedure) on HAART regimen at screening. Note: If no documented pre-screening viral load is available (taken at least 12 weeks after starting the HAART regimen the subject is on at screening and taken within 6 weeks before the screening visit), a pre-screening visit should be scheduled. 6. Screening genotype resistance test results showing none of the following mutations in the protease gene 11I, 32I, 33F, 47V, 50V, 54L, 54M, 74P, 76V, 84V and 89V, known as DRV resistance associated mutations [RAMs]. 7. CD4+ cell count > 50 cells/µL. 8. Subjects have voluntarily signed the ICF. 9. Subjects can comply with the protocol requirements. 10. 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 one or more of the following criteria cannot be selected. 1. Presence of any currently active conditions that fit the definition of the WHO clinical stage 4 with the following exceptions: - Stable cutaneous Kaposi’s Sarcoma (i.e., no internal organ involvement other than oral lesions) that is unlikely to require any form of systemic therapy during the trial time period. - Wasting syndrome. Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed in case the medication used is not part of the disallowed medication. 2. Current or past alcohol and/or drug use which, in the investigator's opinion, could compromise the subject's safety or adherence to the study protocol procedures. 3. Subjects for whom an investigational ARV is part of the current regimen, with the following exceptions if applicable (depending on local regulatory approval): tenofovir, emtricitabine. Note: Participation in observational studies where no treatment is administered is allowed (if approved by sponsor). Upfront approval from the sponsor is needed in case additional blood is taken for other studies. 4. Previous or current use of ENF, tipranavir and/or DRV. 5. Use of disallowed concomitant therapy. 6. Life expectancy of less than 12 months. 7. Pregnant or breast-feeding. 8. Female subject of childbearing potential without use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period. Note: Estrogen hormonal based contraception may not be reliable when taking DRV/rtv, therefore to be eligible for this study, women of childbearing potential should either: (1) use a double barrier method to prevent pregnancy (i.e., use a condom with either diaphragm or cervical cap)*, or (2) use non-estrogen hormonal based contraceptives in combination with a barrier contraceptive (i.e., male condom, diaphragm or cervical cap, or female condom), or (3) use an intra uterine device (IUD) in combination with a barrier contraceptive (i.e., male condom, diaphragm or cervical cap, or female condom), or (4) be only non-heterosexually active, practice heterosexual abstinence, or have a vasectomized partner (confirmed sterile). * a male and female condom should not be used together due to risk of breakage or damage caused by latex friction. Women who are postmenopausal for at least 2 years, and women with total hysterectomy, and women with tubal ligation are considered of non-childbearing potential. 9. Subjects with clinical or laboratory evidence of significantly decreased hepatic function or decompensation (i.e., liver insufficiency), irrespective of liver enzyme levels. 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 study period. Subjects diagnosed with acute viral hepatitis at screening will not be allowed in the trial. Please refer to the package insert with respect to proper care of hepatitis B co-infection in case tenofovir and emtricitabine are included in the OBR. 10. Any active clinically significant disease (e.g., tuberculosis [TB], cardiac dysfunction, pancreatitis, acute viral infections) or findings during screening of medical history or physical examination that, in the investigator’s opinion, would compromise the subjects safety or outcome of the trial. 11. Subjects with a grade 3 or 4 labo
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to demonstrate non-inferiority in virologic response, defined as a confirmed plasma viral load of < 50 HIV-1 RNA copies/mL at Week 48 (as defined by the time ot loss of virologic response [TLOVR] algorithm), with DRV/rtv 800/100 mg q.d. versus DRV/rtv 600/100 mg b.i.d. in early ARV-experienced patients with a non-inferiority margin (delta) of 12%, when administered in combination with an individually selected OBR.;Secondary Objective: The secondary objectives are: - to evaluate safety and tolerabilityover 48 weeks; - to evaluate the durability of efficacy over 48 weeks; - to evaluate the change in viral load from baseline; - to evaluate the percentage subjects with a confirmed plasma viral load < 400 HIV-1 RNA copies/mL; - to evaluate the lipid effects of DRV/rtv q.d. versus b.i.d.; - to compare the immunologic response; - to evaluate resistance characteristics; - to evaluate DRV and ritonavir pharmacokinetics following q.d. and b.i.d. dosing and explore the PK/PD relationship between: 1) DRV and efficacy/safety and 2) ritonavir and safety for b.i.d. and q.d. regimens; - to determine and compare the subject-reported antiretroviral (ARV) medication adherence in subjects treated with DRV/rtv 800/100 mg q.d. versus DRV/rtv 600/100 b.i.d., both administered in combination with an individually selected OBR, at baseline and over 48 weeks.;Primary end point(s): Demonstration of non-inferiority in virologic response | — |
Countries
Austria, Belgium, France, Germany, Hungary, Italy, Spain, United Kingdom
Outcome results
None listed