HIV-1
Conditions
Keywords
HIV Infection, Antiretroviral, HIV-1, AIDS, Children, Rilpivirine (TMC278), Pediatric
Brief summary
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.
Detailed description
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.
Interventions
DRUGRilpivirine
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.
DRUGZidovudine
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).
DRUGAbacavir
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).
DRUGTenofovir disoproxil fumarate
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).
DRUGLamivudine
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).
DRUGEmtricitabine
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).
Sponsors
Janssen Sciences Ireland UC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Has documented human immuno deficiency virus (HIV-1) infection * Patients who meet the following criteria; a) Cohort 1: Patients Aged greater than or equal to (\>=) 12 to less than (\<) 18 years, weight is \>= 32 kilogram (kg), b) Cohort 2; Aged \>= 6 to \< 12 years, weight is \>= 17 kg * Must have HIV-1 plasma viral load at screening greater than equal to 500 HIV-1 ribonucleic acid (RNA) copies/mL * Have not received treatment with a therapeutic HIV vaccine or an HIV drug with the exception of a single dose of nevirapine (NVP) (Cohort 1 and Cohort 2) or up to 6 weeks of zidovudine (AZT) use (Cohort 2 only) prior to screening to prevent mother-to-child transmission (MTCT) * In the judgment of the investigator, it is appropriate to initiate antiretroviral therapy (ARV) therapy based on a patient's medical condition and taking into account guidelines for the treatment of HIV-1 infection in children of this age group
Exclusion criteria
* Any previous use of ARVs with the exception of single dose NVP (Cohort 1 and Cohort 2) or up to 6 weeks of AZT (Cohort 2 only) to prevent MTCT * Plasma viral load at screening greater than 100,000 HIV-1 RNA copies/mL * Documented genotypic evidence of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance at screening or from historical data available in the source documents * Use of disallowed concomitant therapy from 4 weeks prior to the baseline visit * Patient has any currently active Acquired Immunodeficiency Syndrome (AIDS) defining illness * Patient has active tuberculosis and/or is being treated for tuberculosis at screening * Personal history of cardiac disease (including congenital heart disease), or symptomatic arrhythmias, with the exception of sinus arrhythmia; personal history of asymptomatic arrhythmias is excluded if the asymptomatic arrhythmia is clinically significant in the opinion of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1 and 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 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) | Cmax,ss was the maximum observed plasma concentration of rilpivirine at steady state (steady state starting from Day 14). |
| Cohort 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration at Steady State (Cmax,ss) | 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) | 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. |
| Cohorts 1 and 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss) | 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) | 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). |
| Cohort 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohorts 1 and 2: Percentage of Participants With Treatment Adherence >95% Based on Drug Accountability | 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) | 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. |
| Cohorts 1 and 2: Number of Participants With Adverse Events (AEs) | 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) | 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. |
| Cohorts 1 and 2: Change From Baseline in Cluster of Differentiation (CD4+) Cells | Baseline (Day 1) and Week 48 for Cohorts 1 and 2; Week 240 for Cohort 1 alone | 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. |
| 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 | At Week 48 (for Cohorts 1 and 2) and at Week 240 (for Cohort 1 only) | 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. |
| Cohorts 1 and 2: Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL by Food and Drug Administration (FDA) Snapshot Approach | At Week 48 (for Cohorts 1 and 2) and at Week 240 (for Cohort 1 only) | 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. |
| Cohorts 1 and 2: Number of Participants With Post Baseline Genotype Data | 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) | 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. |
Countries
India, Kenya, Romania, South Africa, Thailand, Uganda, Ukraine, United States
Participant flow
Recruitment details
A total of 54 antiretroviral-naïve human Immunodeficiency Virus-1 (HIV-1) infected adolescents (aged greater than or equal to \[\>=\] 12 to less than \[\<\] 18 years) and children (aged \>=6 to \<12 years) were enrolled and treated in Cohort 1 and Cohort 2, respectively.
Pre-assignment details
As of Protocol Amendment 10 (PA 10), for Cohort 2 children \>=6 to \<12 years of age, post Week 48 treatment extension period of 4 years was removed. Hence, the planned efficacy analysis were performed till Week 48 only whereas safety analysis was performed and reported up to Week 240.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg Adolescents (aged \>=12 to \<18 Years) received rilpivirine (RPV) tablet 25 mg orally QD up to 240 weeks in combination with an investigator-selected background regimen containing 2 nucleos(t)ide reverse transcriptase inhibitors (N\[t\]RTIs) (zidovudine \[AZT\], abacavir \[ABC\] or tenofovir disoproxil fumarate \[TDF\] in combination with lamivudine \[3TC\] or emtricitabine \[FTC\]. | 36 |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg Children (aged \>=6 to \<12 years) with body weight \>=25 kg received rilpivirine 25 mg tablet orally QD from 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) in combination with an investigator-selected background regimen containing 2 N\[t\]RTIs: AZT, ABC, or TDF in combination with 3TC or FTC. | 9 |
| Cohort 2 Children (<25 kg): Rilpivirine 25 mg Children (aged \>=6 to \<12 years) with body weight \<25 kg received rilpivirine 25 mg tablet orally QD from 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) in combination with an investigator-selected background regimen containing 2 N\[t\]RTIs: AZT, ABC, or TDF in combination with 3TC or FTC. | 5 |
| Cohort 2 Children (>=20 to <25 kg): Rilpivirine 15 mg Children (aged \>=6 to \<12 years) with body weight \>=20 to \<25 kg received rilpivirine 15 mg (6 tablets of 2.5 mg) orally QD from 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) in combination with an investigator-selected background regimen containing 2 N\[t\]RTIs: AZT, ABC, or TDF in combination with 3TC or FTC. | 2 |
| Cohort 2 Children (<20 kg): Rilpivirine 12.5 mg Children (aged \>=6 to \<12 years) with body weight \<20 kilograms (kg) received rilpivirine 12.5 mg (5 tablets of 2.5 mg) orally QD from 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) in combination with an investigator-selected background regimen containing 2 N\[t\]RTIs: AZT, ABC, or TDF in combination with 3TC or FTC. | 2 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Other | 2 | 1 | 0 | 0 | 0 |
| Overall Study | Participant reached a virologic endpoint | 9 | 2 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort 2 Children (<25 kg): Rilpivirine 25 mg | Cohort 2 Children (>=20 to <25 kg): Rilpivirine 15 mg | Cohort 2 Children (<20 kg): Rilpivirine 12.5 mg | Total | Cohort 1 Adolescents: Rilpivirine 25 mg | Cohort 2 Children (>=25 kg): Rilpivirine 25 mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 9.2 years STANDARD_DEVIATION 0.84 | 6.5 years STANDARD_DEVIATION 0.71 | 6 years STANDARD_DEVIATION 0 | 12.6 years STANDARD_DEVIATION 3.29 | 14.6 years STANDARD_DEVIATION 1.66 | 9.4 years STANDARD_DEVIATION 1.67 |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants | 0 Participants | 0 Participants | 36 Participants | 36 Participants | 0 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Children (2-11 years) | 5 Participants | 2 Participants | 2 Participants | 18 Participants | 0 Participants | 9 Participants |
| Age, Customized From 65 to 84 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 2 Participants | 53 Participants | 36 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 6 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 2 Participants | 48 Participants | 32 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants | 27 Participants | 20 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 1 Participants | 1 Participants | 27 Participants | 16 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 9 | 0 / 5 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 35 / 36 | 8 / 9 | 5 / 5 | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 6 / 36 | 0 / 9 | 0 / 5 | 0 / 2 | 0 / 2 |
Outcome results
Primary
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)
Population: Analysis population included all participants who had taken at least 1 dose of rilpivirine, regardless of their compliance with the protocol and adherence to the dosing regimen. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure. For this OM, participant wise data was only reported because individual data analysis was planned when the 'N' was less than 3.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohort 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss) | Participant 1 | 1933 ng*hr/mL |
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohort 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss) | Participant 2 | 2877 ng*hr/mL |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohort 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss) | Participant 3 | 1710 ng*hr/mL |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohort 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss) | Participant 4 | 2958 ng*hr/mL |
Primary
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)
Population: Analysis population included all participants who had taken at least 1 dose of rilpivirine, regardless of their compliance with the protocol and adherence to the dosing regimen. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure. For this OM, participant wise data was only reported because individual data analysis was planned when the 'N' was less than 3.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohort 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration at Steady State (Cmax,ss) | Participant 1 | 138 nanograms per milliliter (ng/mL) |
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohort 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration at Steady State (Cmax,ss) | Participant 2 | 184 nanograms per milliliter (ng/mL) |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohort 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration at Steady State (Cmax,ss) | Participant 3 | 81.9 nanograms per milliliter (ng/mL) |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohort 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Plasma Concentration at Steady State (Cmax,ss) | Participant 4 | 156 nanograms per milliliter (ng/mL) |
Primary
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)
Population: Population: participants who took at least 1 dose of RPV, regardless of their compliance with protocol \& adherence to dosing regimen. N (Overall number of participants analyzed) = participants evaluable for this OM. In this OM, summarized data for arms Cohort 2 Children (\>=20 to \<25 kg): Rilpivirine 15 mg and Cohort 2 Children (\<20 kg): Rilpivirine 12.5 mg, is not reported as plan was to prepare \& report participant wise data when N was \<3 (which is reported in OM 4).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohorts 1 and 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss) | 1872 nanograms*hour per milliliter (ng*hr/mL) | Standard Deviation 717 |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss) | 2610 nanograms*hour per milliliter (ng*hr/mL) | Standard Deviation 776 |
| Cohort 2 Children (<25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Pharmacokinetics of Rilpivirine as Measured by Area Under the Plasma Concentration Curve at Steady State (AUC24, ss) | 3339 nanograms*hour per milliliter (ng*hr/mL) | Standard Deviation 2233 |
Primary
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)
Population: Population: participants who took at least 1 dose of RPV, regardless of their compliance with protocol \& adherence to dosing regimen. N (Overall number of participants analyzed) =participants evaluable for this outcome measure (OM). In this OM, summarized data for arms Cohort 2 Children (\>=20 to \<25 kg): Rilpivirine 15 mg and Cohort 2 Children (\<20 kg): Rilpivirine 12.5 mg, is not reported as plan was to prepare \& report participant wise data when N was \<3 (which is reported in OM 2).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohorts 1 and 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 109 nanograms per milliliter (ng/mL) | Standard Deviation 38 |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 154 nanograms per milliliter (ng/mL) | Standard Deviation 52.2 |
| Cohort 2 Children (<25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Pharmacokinetics (PK) of Rilpivirine (TMC278) as Measured by Maximum Observed Plasma Concentration at Steady State (Cmax,ss) | 238 nanograms per milliliter (ng/mL) | Standard Deviation 160 |
Secondary
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
Population: Analysis population included all participants who had taken at least 1 dose of RPV, regardless of their compliance with the protocol and adherence to the dosing regimen. Here, 'n' (number analyzed) signifies the number of participants with available data at each specified timepoint. 0 participants in number analyzed field of cohort 2 indicated that Week 240 was not applicable to Cohort 2 as it was beyond the duration of Cohort 2 (i.e., Week 48).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohorts 1 and 2: Change From Baseline in Cluster of Differentiation (CD4+) Cells | Week 48 | 201.2 Cells per microliter | Standard Error 32.87 |
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohorts 1 and 2: Change From Baseline in Cluster of Differentiation (CD4+) Cells | Week 240 | 113.6 Cells per microliter | Standard Error 26.72 |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Change From Baseline in Cluster of Differentiation (CD4+) Cells | Week 48 | 215.9 Cells per microliter | Standard Error 62.42 |
Secondary
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)
Population: Analysis population included all participants who had taken at least 1 dose of RPV, regardless of their compliance with the protocol and adherence to the dosing regimen.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohorts 1 and 2: Number of Participants With Adverse Events (AEs) | 35 Participants |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Number of Participants With Adverse Events (AEs) | 8 Participants |
| Cohort 2 Children (<25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Number of Participants With Adverse Events (AEs) | 5 Participants |
| Cohort 2 Children (>=20 to <25 kg): Rilpivirine 15 mg | Cohorts 1 and 2: Number of Participants With Adverse Events (AEs) | 2 Participants |
| Cohort 2 Children (<20 kg): Rilpivirine 12.5 mg | Cohorts 1 and 2: Number of Participants With Adverse Events (AEs) | 2 Participants |
Secondary
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)
Population: Analysis population included all participants who had taken at least 1 dose of RPV, regardless of their compliance with the protocol and adherence to the dosing regimen. Here, N (Overall number of participants analyzed) signifies participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohorts 1 and 2: Number of Participants With Post Baseline Genotype Data | NNRTI | 9 Participants |
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohorts 1 and 2: Number of Participants With Post Baseline Genotype Data | NRTI | 7 Participants |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Number of Participants With Post Baseline Genotype Data | NNRTI | 5 Participants |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Number of Participants With Post Baseline Genotype Data | NRTI | 4 Participants |
Secondary
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)
Population: Population:participants who took at least 1 dose of RPV, regardless of compliance with protocol \& adherence to dosing regimen. N(Overall number of participants analyzed)=participants evaluable for this OM. n(number analyzed)=number of participants with available data at specified timepoints. In Cohort 2, '0' in 'number analyzed' at Week 240=Week 240 was beyond duration of Cohort 2 (Week 48). '0' in 'number analyzed' of Cohort 1 Week 48=snapshot method was not applicable for Cohort 1 Week 48.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohorts 1 and 2: Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL by Food and Drug Administration (FDA) Snapshot Approach | Week 240 | 53.1 Percentage of participants |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL by Food and Drug Administration (FDA) Snapshot Approach | Week 48 | 72.2 Percentage of participants |
Secondary
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)
Population: Population: participants who took at least 1 dose of RPV, regardless of compliance with protocol \& adherence to dosing regimen. In Cohort 2, 0 in number analyzed field of Week 240 = Week 240 was not applicable as it was beyond duration of Cohort 2 (Week 48); 0 in number analyzed field of Week 48 =planned TLOVR method was not used for data analysis per PA 10 and thus no data was reported in this OM. 'n' (number analyzed) =number of participants with available data at specified timepoints.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg | 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 | Week 48 | 72.2 Percentage of participants |
| Cohort 1 Adolescents: Rilpivirine 25 mg | 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 | Week 240 | 43.8 Percentage of participants |
Secondary
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)
Population: Analysis population included all participants who had taken at least 1 dose of RPV, regardless of their compliance with the protocol and adherence to the dosing regimen. For Cohort 2, 0 in number analyzed field indicated that no participants were available for analysis at Week 240 for Cohort 2 arm because timepoint Week 240 was not applicable to Cohort 2 as it was beyond the duration of Cohort 2 (i.e., Week 48).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohorts 1 and 2: Percentage of Participants With Treatment Adherence >95% Based on Drug Accountability | Up to 240 weeks | 77.8 Percentage of participants |
| Cohort 1 Adolescents: Rilpivirine 25 mg | Cohorts 1 and 2: Percentage of Participants With Treatment Adherence >95% Based on Drug Accountability | Up to 48 weeks | 80.6 Percentage of participants |
| Cohort 2 Children (>=25 kg): Rilpivirine 25 mg | Cohorts 1 and 2: Percentage of Participants With Treatment Adherence >95% Based on Drug Accountability | Up to 48 weeks | 77.8 Percentage of participants |