HIV-1 Infection MedDRA version: 9.1 Level: LLT Classification code 10020161 Term: HIV infection
Conditions
Interventions
Product Name: TMC278 (as the hydrochloric acid salt R314585)
Product Code: GFI-314585-CA-026/F006
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: rilpivirine hydrochloride
CAS Number: 700
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. Boys or girls, aged = 12 to 350 cells/mm³. An example of such situations would include rapidly declining CD4+ cell counts over time. 9. Results from the screening virco® TYPE HIV-1 demonstrate sensitivity to the selected N(t)RTIs using the lower CCO (indicated as “maximal response” on the screening virco®TYPE HIV-1 result) or the BCO (indicated as “susceptible”), whichever is applicable for the chosen background regimen. 10. Subject is able to swallow the TMC278 tablet as a whole (since the tablet cannot be chewed, broken, or crushed). 11. The subject agrees (or their parents/caregivers agree, in case the subject's age is below the cut-off age for consent according to local regulations, in which case the subject is informed and asked to give positive assent) not to start ART before the baseline visit. 12. 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? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no 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. Any previous use of ARVs, with the exception of a single dose of NVP to prevent MTCT. 2. Having documented genotypic evidence of NNRTI resistance at screening or from historical data available in the source documents, i.e., = 1 NNRTI RAM from the following list (the list was compiled on the basis of the list of IAS-USA NNRTI RAMs23 and other relevant publications). A098G V106M Y181C G190S L100I V108I Y181I G190T K101E E138A Y181V P225H K101P E138G Y188C F227C K101Q E138K Y188H M230I K103H E138Q Y188L M230L K103N E138R G190A P236L K103S V179E G190C K238N K103T V179D G190E K238T V106A V179T G190Q Y318K 3. Previously documented HIV-2 infection. 4. Subject has a positive HLA-B*5701 test at screening (when the invesigator considers ABC/3TC as a background regimen). In case of a positive test, ABC/3TC cannot be administered, but instead, the investigator can select AZT/3TC as the background regimen. HLA-B*5701 testing is not required for subjects with prior documented negative results. 5. Use of disallowed concomitant therapy from 4 weeks prior to the baseline visit. 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.8. Subject has any currently active Acquired Immunodeficiency Syndrome (AIDS) defining illness (Category C conditions according to the Centers for Disease Control and Prevention [CDC] Classification System for HIV-Infection 1993). 9. Any active clinically significant disease (e.g., pancreatitis, cardiac dysfunction, active and significant psychiatric disorders, clinical suspicion of adrenal insufficiency, hepatic impairment), or findings during screening or medical history that in the investigator’s opinion, would compromise the outcome of the trial. 10. Subject has a known or suspected acute (primary) HIV-1 infection. 11. Any current or history of adrenal disorder. 12. Previously demonstrated clinically significant allergy or hypersensitivity to any of the components of the investigational medication (TMC278) or the selected NRTIs. In this last case, the other N(t)RTI may be selected. 13. Receipt of any investigational drug or investigational vaccine within 90 days prior to the first administration of TMC278. 14. Pregnant or breastfeeding girl. 15. Heterosexually active girls of childbearing potential without the use of effective birth control methods or not willing to continue practicing these birth control methods from screening onwards until at least 30 days after last intake of TMC278. 16. Heterosexually active boys without the use of effective birth control methods or not willing to continue practicing these birth control methods from screening onwards until 30 days after last intake of TMC278. 17. Any grade 3 or 4 laboratory toxicity according to the Division of AIDS (DAIDS) grading table (see Section 8.2, Addendum 2), except for: - grade 3 absolute neutrophil count; - grade 3 platelets; - grade 3 glucose elevation in diabetics; - asymptomatic grade 3 pancreatic amylase elevation; - asymptomatic grade 3 triglyceride / cholesterol / glucose elevation; - asymptomatic grade 4 triglyceride elevation. 18. Subject has active tuberculosis and/or is being treated for tuberculosis at screening. 19. Subject has one or more of the following risk factors for QTc prolongation: - a confirmed pr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of Part 1 are: - To evaluate the steady-state pharmacokinetics of TMC278 25 mg q.d. in subjects aged = 12 to < 18 years; - to evaluate short-term (2 weeks) safety, and antiviral activity of TMC278 in this age group. The objectives of Part 2 are: - To evaluate long-term safety and efficacy of TMC278 over a 24 and 48 week treatment period; - to evaluate immunologic changes (as measured by CD4+ cell parameters) over 24 and 48 weeks of treatment with TMC278; - to assess the evolution of viral genotype and phenotype over 24 and 48 weeks of treatment with TMC278; - to evaluate pharmacokinetics (by means of population pharmacokinetics) and pharmacokinetic-pharmacodynamic relationships for safety and efficacy of TMC278; - to evaluate treatment adherence as measured by the Study Adherence Questionnaire for Children and Teenagers (see Addendum 7: Study Adherence Questionnaire for Children and Teenagers);Secondary Objective: ;Primary end point(s): | — |
Countries
Spain
Outcome results
None listed