TMC125-TiDP35-C213: Safety and Antiviral Activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents
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|ClinicalTrials.gov Identifier: NCT00665847|
Recruitment Status : Completed
First Posted : April 24, 2008
Results First Posted : December 21, 2012
Last Update Posted : April 23, 2015
|Condition or disease||Intervention/treatment||Phase|
|HIV-1||Drug: Etravirine (TMC125) Drug: Optimized background regimen (OBR)||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||103 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II, Open-label Trial, to Evaluate the Safety, Tolerability and Antiviral Activity of TMC125 in Antiretroviral Experienced HIV-1 Infected Children and Adolescents|
|Study Start Date :||November 2008|
|Actual Primary Completion Date :||May 2011|
|Actual Study Completion Date :||August 2011|
|Experimental: Etravirine (TMC125)||
Drug: Etravirine (TMC125)
Patients will be dosed by body weight , i.e. 5.2 mg/kg twice daily (b.i.d.) up to a maximum of 200 mg b.i.d. for 48 weeks.
Drug: Optimized background regimen (OBR)
An investigator-selected optimized background regimen (OBR) comprising of a low-dose ritonavir (rtv)-boosted protease inhibitor (PI) (either lopinavir [LPV], darunavir [DRV], atazanavir [ATV] or saquinavir [SQV]) in combination with nucleos(t)ide reverse transcriptase inhibitor(s) (N[t]RTIs) to be dosed according to the drugs individual package inserts for 48 weeks.
- The Number of Patients With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 48 weeks ]A treatment-emergent adverse event (TEAE) was defined as an event that occurred in the 48-week treatment period during which it emerged (i.e. started or worsened in severity, relation, or other attribute), and not in the subsequent study periods, even if the event continued to be present. Adverse events were graded from 1 to 4 in severity using the Division of Acquired Immunodeficiency Syndrome severity scale (grade 1 being less severe and grade 4 being more severe). ETR=etravirine/TMC125; OBR=optimized background regimen
- The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 48 weeks ]The percentage of patients with a treatment-emergent adverse event (TEAE) (defined as an event that occurred in the 48-week treatment period during which it emerged [i.e. started or worsened in severity, relation, or other attribute], and not in the subsequent study periods, even if the event continued to be present] are provided below. Adverse events were graded from 1 to 4 in severity using the Division of Acquired Immunodeficiency Syndrome severity scale (grade 1 being less severe and grade 4 being more severe). ETR=etravirine/TMC125; OBR=optimized background regimen
- Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Area Under the Plasma Concentration-time Curve Over 12 Hours at Steady-state (AUC12h) [ Time Frame: Weeks 4-48 ]The AUC12h is a Bayesian estimation based on a population pharmacokinetic model and sparse samples collected at each visit over the duration of trial. For each sparse sample taken, the time blood sample was recorded as well as the time of etravirine intake just prior to the time of blood sample.
- Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Trough Plasma Concentration (C0h) [ Time Frame: Week 48 ]
- Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Maximum Plasma Concentration (Cmax) [ Time Frame: Week 4 ]Etravirine/TMC125 (ETR) Cmax was approximated for each individual using the median value of plasma ETR concentrations taken 4 hours postdose (± 1 hour), when available, on the day of the Week 4 visit as shown in the table below.
- Percentage of Patients With Virologic Response at Week 24 [ Time Frame: Week 24 ]Virologic response was defined as the percentage of patients with plasma viral load < 50 copies/mL at Week 24 calculated according to the non-completer=failure (NC=F) imputation method.
- Change From Baseline in Human Immunodeficiency Virus - Type 1 (HIV-1) Ribonucleic Acid (RNA) in Plasma Over Time [ Time Frame: Baseline, Week 48 ]
- The Change From Baseline in CD4 Cell Counts Over Time [ Time Frame: Baseline, Week 48 ]
- The Emergence of Non-nucleoside Reverse Transcriptase Inhibitor Resistance-associated Mutations (NNRTI RAMs) in Patients Classified as Virologic Failures [ Time Frame: Baseline and Endpoint (up to Week 48) ]Virologic failure (lack of response) was defined as: plasma viral load decline of < 0.5 log10 from Baseline by Week 8 and/or plasma viral load decline of <1.0 log10 from Baseline by Week 12. Virologic failure (loss of response) was defined as 2 consecutive measurements of plasma viral load > 0.5 log10 above the nadir after a minimum of 12 weeks of treatment. The table below provides data for 41 viologic failures of which 30 had mutation data available. In the table below, only the 4 most frequently emerging mutations are presented (emerging in at least 3 patients).
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Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00665847
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|Study Director:||Tibotec Pharmaceuticals, Ireland Clinical Trial||Tibotec Pharmaceuticals, Ireland|