The purpose of this study is to evaluate the pharmacokinetics, safety and antiviral activity of rilpivirine (TMC278) 25 milligram (mg) or adjusted dose once daily in combination with an investigator-selected background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors (N\[t\]RTIs) (zidovudine \[AZT\], abacavir \[ABC\], or tenofovir disoproxil fumarate \[TDF\] in combination with lamivudine \[3TC\] or emtricitabine \[FTC\] in antiretroviral (ARV) treatment-naïve adolescents and children aged greater than or equal to (\>=) 6 to less than (\<) 18 years.
This is a Phase II, open-label (all people involved know the identity of the assigned drug) and single arm study. The study will consist of a screening period of maximum 8 weeks, an initial treatment period of 48 weeks, a post week 48 treatment extension period of 4 years (Cohort 1 only), and a 4 week follow-up (cohort 2 only) period. Participants who withdraw from the trial on or before the Week 48 visit or subjects with ongoing (serious) adverse events (\[S\]AEs), laboratory abnormalities, or viral load increase at the last on-treatment visit in the extension, will be seen for a follow-up visit 4 weeks later. The initial 48-week treatment period will be structured into 2 age Cohorts; Cohort 1 (Aged greater than or equal to \[\>=\] 12 to less than \[\<\] 18 years) and Cohort 2 (Children Aged \>= 6 to \< 12 years). The trial is designed to evaluate the steady-state pharmacokinetic (PK) profile (based on intensive PK analysis) and the short-term safety and antiviral activity of rilpivirine (RPV). Participants will receive RPV 25 milligram (mg), or weight-adjusted dose orally once daily for 240 weeks when administered in combination with 2 nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs). The trial will also evaluate long-term (48 weeks and 240 weeks \[Cohort 1\]) safety, efficacy, and pharmacokinetics of rilpivirine in combination with the background regimen of 2 NRTIs. Patients safety will be monitored throughout the study and during the follow up visits.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
54
Patients will receive rilpivirine (RPV) tablet 25 milligram dose or an adjusted dose orally once daily in Cohort 1 (adolescents aged \>=12 to \<18 years) up to 240 weeks. Patients will receive RPV weight-adjusted dose orally once daily in Cohort 2 (children aged \>=6 to \<12 years) or 25 mg once daily for up to 48 weeks.
Type=exact, form= appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).
Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).
Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for 240 weeks (Cohort 1).
Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).
Type=exact, form=appropriate pediatric formulation, unit=mg, route=oral. The patients may receive this selected NRTI together with another NRTI once daily for up to 48 weeks (Cohort 2) and 240 weeks (Cohort 1).
Unnamed facility
Syracuse, New York, United States
Unnamed facility
Memphis, Tennessee, United States
Unnamed facility
Chennai, India
Unnamed facility
Mangalore, India
Unnamed facility
Nairobi, Kenya
Unnamed facility
Bucharest, Romania
Unnamed facility
Bloemfontein, South Africa
Unnamed facility
Dundee, South Africa
Unnamed facility
Middelburg, South Africa
Unnamed facility
Pretoria, South Africa
...and 7 more locations
Cohorts 1 and 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Cmax,ss was the maximum observed plasma concentration of rilpivirine at steady state (steady state starting from Day 14).
Time frame: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
Cohort 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration at Steady State (Cmax,ss)
Cmax,ss was the maximum plasma concentration of rilpivirine at steady state (steady state starting from Day 14). In the below data table, the measure type "Number" corresponds to Cmax,ss concentration.
Time frame: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
Cohorts 1 and 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss)
AUC24,ss was defined as the area under the plasma concentration versus time curve from time 0 to 24 hours post dosing of rilpivirine at steady state (steady state starting from Day 14).
Time frame: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
Cohort 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss)
AUC24,ss was defined as the area under the plasma concentration versus time curve from time 0 to 24 hours post dosing of rilpivirine at steady state (steady state starting from Day 14). In the below data table, the measure type "Number" corresponds to AUC24, ss concentration.
Time frame: Pre-dose, 0, 2, 4, 5, 6, 9, 12 and 24 hours post dose at steady-state (any time during Day 14 to Day 18)
Cohorts 1 and 2: Number of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product and did not necessarily have a causal relationship with the treatment.
Time frame: Cohort 1: From baseline (Day 1) up to Week 240; Cohort 2: From Baseline (Day 1) up to 240 weeks (for participants recruited up to protocol amendment 9); up to 48 weeks (for participants recruited after implementation of protocol amendment 10)
Cohorts 1 and 2: Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) Level Less Than (<) 50 Copies/mL by Time to Loss of Virologic Response (TLOVR) Method
Percentage of participants with plasma HIV-1 RNA \<50 copies per milliliter (Copies/mL) assessed by TLOVR method was reported. TLOVR requires sustained HIV-1 RNA \< 50 copies/mL; confirmed HIV-1 RNA more than or equal to (\>=) 50 copies/mL is considered as non-response (rebound); participant was considered non-responder after permanent discontinuation. Responder is defined as the participant with confirmed plasma viral load \<50 copies/mL. As planned, combined data for cohort 2 was collected, analyzed and reported for this outcome measure.
Time frame: At Week 48 (for Cohorts 1 and 2) and at Week 240 (for Cohort 1 only)
Cohorts 1 and 2: Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL by Food and Drug Administration (FDA) Snapshot Approach
Percentage of participants with a HIV-1 RNA \<50 copies per mL were assessed using FDA snapshot approach which defines a participant's virologic response status using only the viral load at the predefined time point within a window of time, along with study drug discontinuation status. If HIV-1 RNA level is \< 50 copies per mL, it is considered as virologic success as per the snapshot approach. As planned, combined data for cohort 2 was collected, analyzed and reported for this outcome measure.
Time frame: At Week 48 (for Cohorts 1 and 2) and at Week 240 (for Cohort 1 only)
Cohorts 1 and 2: Number of Participants With Post Baseline Genotype Data
Number of participants with post baseline genotype (nucleoside analogue reverse transcriptase inhibitors \[NRTI\] and non-nucleoside reverse transcriptase inhibitors \[NNRTI\] resistance) data were reported. As planned, combined data for cohort 2 was collected, analyzed and reported for this outcome measure.
Time frame: Cohort 1: From baseline (Day 1) up to Week 240; Cohort 2: From baseline (Day 1) up to 240 weeks (for participants recruited up to protocol amendment 9); up to 48 weeks (for participants recruited after implementation of protocol amendment 10)
Cohorts 1 and 2: Percentage of Participants With Treatment Adherence >95% Based on Drug Accountability
Percentage of participants with treatment adherence \>95% based on drug accountability from baseline up to Week 240 for Cohort 1 and from baseline up to 240 weeks (for participants recruited up to protocol amendment 9); up to 48 weeks (for participants recruited after implementation of protocol amendment 10) for cohort 2 were reported. Treatment adherence was defined as having a treatment adherence of greater than (\>) 95 percent (%) by pill count. Drug accountability included dispensation, receipt, and return, or if applicable, destruction of RPV documented by using the appropriate forms. As planned, combined data for cohort 2 was collected, analyzed and reported for this outcome measure.
Time frame: Cohort 1: From baseline (Day 1) up to Week 240; Cohort 2: From baseline (Day 1) up to 240 weeks (for participants recruited up to protocol amendment 9); up to 48 weeks (for participants recruited after implementation of protocol amendment 10)
Cohorts 1 and 2: Change From Baseline in Cluster of Differentiation (CD4+) Cells
The immunologic change was determined by changes in Cluster of CD4+ cell count using non-completer =failure imputation, that is discontinuation was imputed with baseline value resulting in change=0, other missing data using last observation carried forward (LOCF). Change from baseline in CD4+ cell count at Week 48 for Cohort 1 and 2; and at Week 240 for Cohort 1 only were assessed. As planned, combined data for cohort 2 was collected, analyzed and reported for this outcome measure.
Time frame: Baseline (Day 1) and Week 48 for Cohorts 1 and 2; Week 240 for Cohort 1 alone
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