HIV-1 MedDRA version: 8.1 Level: LLT Classification code 10020160 Term: HIV disease
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 (F016)
Other descripti
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 and girls, aged between 6 and 17 years. 2. Subjects with documented HIV-1 infection. 3. Body weight Part I: = 20 to 1000 copies/mL. 7. Parents or legal representative and trial subjects (where appropriate, depending on age and local regulation) willing and able to give consent. Children will be informed about the trial and asked to give positive assent as per description in Chapter II, section 6.4 8. Subjects can comply with the protocol requirements. 9. General medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial. 10. Female subjects who are sexually active and able to become pregnant must use a safe and effective birth control method, such as medically accepted barrier methods of contraception (e.g., diaphragm, and condom) during the study. Hormonal birth control alone would not be considered adequate, as the interaction between study drug and hormonal birth control is not available. 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. Part I: Use of the NNRTI efavirenz as part of the current regimen is not allowed. Part II: Use of efavirenz as part of the current regimen is allowed (see Table 2). 2. Presence of any currently active AIDS defining illness [Category C conditions according to the CDC Classification System for HIV Infection 1993 or according to the 1994 revised CDC Classification System for HIV infection in children less than 13 years of age (see Addendum 6; Section 7.6)]: Note: An AIDS defining illness not clinically stabilized for at least 30 days will be considered as currently active. Note: Primary and secondary prophylaxis for an AIDS defining illness is allowed in cases where the medication administered is not part of the disallowed medications (see Section 5.5.12). 3. Active substance use as determined by the investigator during anamnesis that includes but is not limited to daily or frequent alcohol intake, use of solvents, barbiturate, amphetamine, and recreational or narcotic drugs. Note: Prescribed use of methadone is allowed (see Table 2). 4. Use of disallowed concomitant therapy (see Section 5.5.12). 5. Use of any antiretroviral and non-antiretroviral investigational agents within 30 days prior to screening, except for tenofovir, tipranavir, atazanavir and fosamprenavir. Note: TMC114 should not be used within 14 days following the use of tipranavir. A minimal 14-day washout period is required in which tipranavir must be either interrupted or substituted to an investigator selected PI regimen until the baseline visit (Day 1). 6. Life expectancy of less than 6 months. 7. Co-enrollment in other clinical and/or cohort trials without written permission of the sponsor. 8. Pregnancy or breastfeeding. 9. Any active clinically significant disease (e.g., 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 subject’s safety or outcome of the trial. 10. Previously demonstrated clinically significant allergy or hypersensitivity to any of the excipients of the investigational medication (TMC114) or ritonavir. Note: TMC114 is a sulfonamide. Subjects who previously experienced a sulfonamide allergy will be allowed to enter the trial. To date, no potential for cross sensitivity between drugs in the sulfonamide class and TMC114 has been identified in subjects participating in phase II trials. 11. Subjects with documented hepatic impairment. Note: subjects co-infected with chronic hepatitis B or C (determined by hepatitis B surface antigen, anti core-hepatitis B IgG antibody and hepatitis C antibody) will be allowed to enter the trial if their condition is clinically stable, and they are not expected to require treatment during the study period and have ALT or AST levels < 3 x ULN. Subjects diagnosed with acute viral hepatitis at screening will not be allowed in the trial (e.g., hepatitis A IgM antibody). 12. Subjects with the following laboratory abnormalities as defined by the DAIDS grading scheme: · any grade 3 or 4 toxicity with the following exceptions unless clinical assessment foresees an immediate health risk to the subject: - subjects with pre-existing diabetes or asymptomatic glucose elevati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PART I OBJECTIVES The objectives are: - To evaluate the pharmacokinetic profile of two different doses of TMC114 in combination with low-dose ritonavir administered b.i.d. in the pediatric population at steady-state: AUC12h, Cmax and Cmin; - To provide dose recommendation of TMC114 per body weight in pediatric subjects of = 20 kg to < 50 kg; - To evaluate short-term safety, tolerability and antiviral activity of two different doses of TMC114/rtv administered b.i.d. in treatment-experienced pediatric subjects. PART II PRIMARY OBJECTIVE - To evaluate long-term safety, tolerability and efficacy of TMC114 in combination with low-dose ritonavir administered b.i.d. and other ARV agents over a 24-week treatment period at the recommended pediatric (= 20 kg to < 50 kg) and adult (= 50 kg) doses.;Secondary Objective: PART II SECONDARY OBJECTIVES - To evaluate long-term safety, tolerability and efficacy of TMC114 in combination with low-dose ritonavir administered b.i.d. and other ARV agents over a 48-week treatment period at the recommended pediatric (= 20 kg to < 50 kg) and adult (= 50 kg) doses; - To evaluate immunology, resistance characteristics, pharmacokinetic parameters and pharmacokinetic/pharmacodynamic (PD) relationships of TMC114/rtv over 48 weeks of treatment. ;Primary end point(s): FOR PART I The primary efficacy parameter will be virologic response at Week 2, defined as a drop in viral load (copies/mL) of at least 0.5 log10 versus baseline. The main analysis will be a non-completing = failure analysis (NC=F); i.e. all subjects who have discontinued the trial prematurely will be considered as failures. FOR PART II The primary efficacy parameter will be confirmed virologic response (TLOVR) at Week 24, defined as a drop in viral load (copies/mL) of at least 1 log 10 versus baseline. | — |
Countries
Italy, Spain, United Kingdom
Outcome results
None listed