HIV
Conditions
Brief summary
The purpose of this study is to evaluate the steady state pharmacokinetics (PK) of rilpivirine (RPV) and determine the appropriate dose of RPV in combination with other antiretrovirals (ARVs) in participants aged greater than or equal to 2 to less than 12 years and to evaluate the safety and tolerability of RPV in combination with other ARVs in participants of same age group over a 48-week treatment period with primary endpoint at Week 24.
Detailed description
Participants infected with human immunodeficiency virus type 1 (HIV-1) are routinely treated with combinations of multiple drugs which reduces HIV-1 ribonucleic acid (RNA) to undetectable levels in a substantial proportion of participants and counteracts the risk of viral resistance development. RPV is a potent non-nucleoside reverse transcriptase inhibitor (NNRTI) with in vitro activity against wild type (WT) HIV-1 and against NNRTI-resistant HIV-1 mutants. A medical need still exists for the development of age/weight appropriate formulations in children less than (\<) 12 years of age. In this study, participants will switch to RPV plus other ARVs. The primary analysis will be performed at Week 24. A participant will be considered to have completed the study if he or she has completed assessments at Week 48 of the study intervention phase. The total study duration for each participant, including screening and study intervention phases, will be approximately 54 weeks. Key efficacy assessments include determination of plasma HIV-1 RNA viral load and measurement of CD4+ cell count. Key safety assessments will include the monitoring of (serious) adverse events (\[S\]AEs) and HIV-related events, clinical laboratory tests, cardiovascular safety monitoring (vital signs and 12 lead electrocardiogram \[ECGs\]), and physical examination (including growth).
Interventions
DRUGRilpivirine
Rilpivirine 25 mg tablets for the 25 mg daily dose, or tablets for or a weight-adjusted dose. Administered orally once daily.
DRUGARV Background Regimen
The investigator-selected ARVs, including but not limited to N(t)RTIs (example, azidothymidine \[AZT\], abacavir \[ABC\], tenofovir alafenamide \[TAF\], or tenofovir disoproxil fumarate \[TDF\] in combination with emtricitabine \[FTC\] or lamivudine \[3TC\]), whichever are approved and marketed or considered local standard of care for children aged between 2 and \< 12 years in a particular country are to be administered. Integrase inhibitors (for example, dolutegravir \[DTG\] or raltegravir) can also be administered in combination with RPV, as appropriate.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Weighing at least 10 kilogram (kg) at screening * Have documented chronic Human Immunodeficiency Virus (HIV-1) infection * On a stable antiretroviral (ARV) regimen for at least 6 months prior to screening and virologically suppressed with documented evidence of at least 2 plasma viral loads less than (\<) 50 HIV-1 ribonucleic acid (RNA) copies/milliliter (mL): one within 2-12 months prior to screening and one at screening * Can switch from any ARV class * Never been treated with a therapeutic HIV vaccine * Historical HIV-1 genotyping result at screening for children aged \>=2 to \<6 years (and for children aged \>=6 to \<12 years if a historical HIV-1 genotyping result is available at screening) must demonstrate sensitivity to RPV and to the selected background ARVs
Exclusion criteria
* Have previously documented HIV-2 infection * Have known or suspected acute (primary) HIV-1 infection * Taken any disallowed concomitant therapies within 4 weeks before the planned first dose of study intervention * Any current or history of adrenal disorder * A history of virologic failure to ARVs with or without availability of an HIV-1 genotype result at the time of failure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 12.5 mg (for <20 kg Group) | Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4) | AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing \<20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the \<20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
| Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 15 mg (for <20 kg Group) | Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4) | AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
| Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 15 mg (for 20 to <25 mg Group) | Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4) | AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
| Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 25 mg (for >=25 kg Group) | Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4) | AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for <20 kg Group) | Predose at anytime during Day 28 to Day 32 (Week 4) | C(0h) was defined as the predose plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
| Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for 20 to <25 kg Group) | Predose at anytime during Day 28 to Day 32 (Week 4) | C(0h) was defined as the predose plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
| Predose Plasma Concentration (C[0h]) of Rilpivirine 25 mg (for >=25 kg Group) | Predose at anytime during Day 28 to Day 32 (Week 4) | C(0h) was defined as the predose plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
| Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 12.5 mg (for <20 kg Group) | Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4) | Cmax was defined as the maximum observed plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing \<20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the \<20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
| Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for <20 kg Group) | Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4) | Cmax was defined as the maximum observed plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
| Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48 | From Day 1 up to Weeks 24 and 48 | Percentage of participants with a HIV-1 RNA less than (\<) 50 copies per mL and greater than or equal to (\>=)50 copies/mL were assessed using Food and Drug Administration (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. HIV-1 RNA level \<50 copies per mL, was considered as virologic success and \>= 50 copies/mL was considered as virological failure as per the snapshot approach. The FDA snapshot analysis at Week 24 and Week 48 was based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48). |
| Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 25 mg (for >=25 kg Group) | Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4) | Cmax was defined as the maximum observed plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
| Percentage of Participants With Viral Genotype at the Time of Virologic Failure at Weeks 24 and 48 | Weeks 24 and 48 | Percentage of participants with viral genotype at the time of virologic failure (that is, HIV 1 RNA \>=50 copies/mL and \>=400 copies/mL) per FDA snapshot approach were reported. Confirmed virologic failure was defined as 2 consecutive HIV-1 RNA plasma viral load measurements \>=200 copies/mL and suspected virologic failure was defined as HIV-1 RNA \>=200 copies/mL. No participant achieved virologic failure hence this outcome measure could not be evaluated. |
| Percentage of Participants With Treatment Adherence >95% Based on Tablet Count up to Weeks 24 and 48 | From Day 1 up to Weeks 24 and 48 | Percentage of participants with treatment adherence greater than (\>) 95 percent (%) as assessed by tablet count (study intervention accountability) up to Weeks 24 and 48 of study treatment were reported. Treatment adherence was defined as having a treatment adherence of \>95% by tablet count. |
| Change From Baseline in Percentage of Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | From baseline (Day 1) up to Weeks 24 and 48 | The immunologic change was determined by changes in CD4+ cell count using non-completer = failure imputation, that was, missing values after discontinuation were imputed with the baseline value, thus resulting in a 0 change. For intermittent missing data, last observation carried forward (LOCF) approach was applied. |
| Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for 20 to <25 mg Group) | Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4) | Cmax was defined as the maximum observed plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
| Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48 | From Day 1 up to Weeks 24 and 48 | Percentage of participants with viral load (plasma HIV-1 RNA levels) \<400 copies/mL and \>=400 copies/mL were assessed by the 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. HIV-1 RNA level \<400 copies per mL, was considered as virologic success and \>=400 copies/mL was considered as virological failure as per the snapshot approach. The FDA snapshot analysis at Week 24 and Week 48 was based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48). |
| Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | From baseline (Day 1) up to Weeks 24 and 48 | The immunologic change was determined by changes in CD4+ cell count using non-completer = failure imputation, that was, missing values after discontinuation were imputed with the baseline value, thus resulting in a 0 change. For intermittent missing data, last observation carried forward (LOCF) approach was applied. |
| Predose Plasma Concentration (C[0h]) of Rilpivirine 12.5 mg (for <20 kg Group) | Predose at anytime during Day 28 to Day 32 (Week 4) | C(0h) was defined as the predose plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing \<20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the \<20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen. |
Countries
Italy, Portugal, South Africa, Spain, Thailand, Uganda
Participant flow
Pre-assignment details
Participant flow is based on the initial administered dose, irrespective of subsequent dose-alterations. Out of the 2 participants weighing \<20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the \<20 kg rilpivirine 15 mg group in the Participant flow section, whereas it was counted in the \<20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments reported in the outcome measure section.
Participants by arm
| Arm | Count |
|---|---|
| Rilpivirine Participants weighing less than (\<) 20 kilograms (kg) received rilpivirine 12.5 milligrams (mg) or 15 mg; 20 to \<25 kg received rilpivirine 15 mg; greater than equal to (\>=) 25 kg received rilpivirine 25 mg orally once daily in combination with investigator-selected antiretrovirals (ARVs), including but not limited to nucleoside/nucleotide reverse transcriptase inhibitor (N\[t\]RTIs) (example, azidothymidine \[AZT\], abacavir \[ABC\], tenofovir alafenamide \[TAF\], or tenofovir disoproxil fumarate \[TDF\] in combination with emtricitabine \[FTC\] or lamivudine \[3TC\]), whichever were approved and marketed or considered local standard of care for children aged between \>=2 and \<12 years in a particular country. Integrase inhibitors (for example, dolutegravir \[DTG\] or raltegravir) were administered in combination with rilpivirine as appropriate. The overall treatment duration of the study was 52 weeks. | 26 |
| Total | 26 |
Baseline characteristics
| Characteristic | Rilpivirine |
|---|---|
| Age, Continuous | 9.5 years STANDARD_DEVIATION 1.83 |
| Age, Customized 85 years and over | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 0 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants |
| Age, Customized Children (2-12 years) | 26 Participants |
| Age, Customized From 65 to 84 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment Italy | 5 Participants |
| Region of Enrollment Portugal | 1 Participants |
| Region of Enrollment South Africa | 8 Participants |
| Region of Enrollment Spain | 3 Participants |
| Region of Enrollment Thailand | 7 Participants |
| Region of Enrollment Uganda | 2 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 26 |
| other Total, other adverse events | 11 / 26 |
| serious Total, serious adverse events | 0 / 26 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 12.5 mg (for <20 kg Group)
AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing \<20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the \<20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Population: Full analysis set (FAS): who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 12.5 mg (for <20 kg Group) | Participant 1 | 4116 nanograms*hour/milliliter (ng*h/mL) |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 12.5 mg (for <20 kg Group) | Participant 2 | 4646 nanograms*hour/milliliter (ng*h/mL) |
Primary
Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 15 mg (for <20 kg Group)
AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 15 mg (for <20 kg Group) | 3494 ng*h/mL |
Primary
Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 15 mg (for 20 to <25 mg Group)
AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 15 mg (for 20 to <25 mg Group) | 3506 ng*h/mL | Standard Deviation 946 |
Primary
Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 25 mg (for >=25 kg Group)
AUC(0-24h) was defined the area under the plasma concentration-time curve from time of administration up to 24 hours postdose of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 25 mg (for >=25 kg Group) | Participant 1 | 4514 ng*h/mL |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Area Under the Plasma Concentration-time Curve From Time of Administration up to 24 Hours Postdose (AUC[0-24h]) of Rilpivirine 25 mg (for >=25 kg Group) | Participant 2 | 5644 ng*h/mL |
Secondary
Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48
The immunologic change was determined by changes in CD4+ cell count using non-completer = failure imputation, that was, missing values after discontinuation were imputed with the baseline value, thus resulting in a 0 change. For intermittent missing data, last observation carried forward (LOCF) approach was applied.
Time frame: From baseline (Day 1) up to Weeks 24 and 48
Population: FAS included all participants who had taken at least 1 dose of rilpivirine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | Week 24 | 313.0 Cells/cubic millimeter | — |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | Week 48 | 279.0 Cells/cubic millimeter | — |
| Rilpivirine: >=6 to <12 Years | Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | Week 24 | 26.3 Cells/cubic millimeter | Standard Error 32.1 |
| Rilpivirine: >=6 to <12 Years | Change From Baseline in Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | Week 48 | -19.9 Cells/cubic millimeter | Standard Error 28.52 |
Secondary
Change From Baseline in Percentage of Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48
The immunologic change was determined by changes in CD4+ cell count using non-completer = failure imputation, that was, missing values after discontinuation were imputed with the baseline value, thus resulting in a 0 change. For intermittent missing data, last observation carried forward (LOCF) approach was applied.
Time frame: From baseline (Day 1) up to Weeks 24 and 48
Population: FAS included all participants who had taken at least 1 dose of rilpivirine.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Change From Baseline in Percentage of Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | Week 24 | 5.3 Percentage of lymphocytes | — |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Change From Baseline in Percentage of Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | Week 48 | 6.4 Percentage of lymphocytes | — |
| Rilpivirine: >=6 to <12 Years | Change From Baseline in Percentage of Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | Week 24 | 1.2 Percentage of lymphocytes | Standard Error 1.04 |
| Rilpivirine: >=6 to <12 Years | Change From Baseline in Percentage of Cluster of Differentiation 4 (CD4+) Cell Count up to Week 24 and Week 48 | Week 48 | 0.7 Percentage of lymphocytes | Standard Error 1.14 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 12.5 mg (for <20 kg Group)
Cmax was defined as the maximum observed plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing \<20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the \<20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 12.5 mg (for <20 kg Group) | Participant 1 | 273 ng/mL |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 12.5 mg (for <20 kg Group) | Participant 2 | 318 ng/mL |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for <20 kg Group)
Cmax was defined as the maximum observed plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for <20 kg Group) | 214 ng/mL |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for 20 to <25 mg Group)
Cmax was defined as the maximum observed plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 15 mg (for 20 to <25 mg Group) | 217 ng/mL | Standard Deviation 43.1 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 25 mg (for >=25 kg Group)
Cmax was defined as the maximum observed plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose up to 24 hour post-dose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 25 mg (for >=25 kg Group) | Participant 1 | 309 ng/mL |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Maximum Observed Plasma Concentration (Cmax) of Rilpivirine 25 mg (for >=25 kg Group) | Participant 2 | 418 ng/mL |
Secondary
Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48
Percentage of participants with viral load (plasma HIV-1 RNA levels) \<400 copies/mL and \>=400 copies/mL were assessed by the 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. HIV-1 RNA level \<400 copies per mL, was considered as virologic success and \>=400 copies/mL was considered as virological failure as per the snapshot approach. The FDA snapshot analysis at Week 24 and Week 48 was based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48).
Time frame: From Day 1 up to Weeks 24 and 48
Population: FAS included all participants who had taken at least 1 dose of rilpivirine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48 | Week 24: <400 copies/mL | 100.0 Percentage of participants |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48 | Week 48: >=400 copies/mL | 0.0 Percentage of participants |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48 | Week 24: >=400 copies/mL | 0.0 Percentage of participants |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48 | Week 48: <400 copies/mL | 100.0 Percentage of participants |
| Rilpivirine: >=6 to <12 Years | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48 | Week 24: <400 copies/mL | 100.0 Percentage of participants |
| Rilpivirine: >=6 to <12 Years | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48 | Week 48: <400 copies/mL | 100.0 Percentage of participants |
| Rilpivirine: >=6 to <12 Years | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48 | Week 48: >=400 copies/mL | 0.0 Percentage of participants |
| Rilpivirine: >=6 to <12 Years | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <400 and >=400 Copies/mL Through Weeks 24 and 48 | Week 24: >=400 copies/mL | 0.0 Percentage of participants |
Secondary
Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48
Percentage of participants with a HIV-1 RNA less than (\<) 50 copies per mL and greater than or equal to (\>=)50 copies/mL were assessed using Food and Drug Administration (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. HIV-1 RNA level \<50 copies per mL, was considered as virologic success and \>= 50 copies/mL was considered as virological failure as per the snapshot approach. The FDA snapshot analysis at Week 24 and Week 48 was based on the last observed plasma viral load data within the visit window (that is, Weeks 24 and 48).
Time frame: From Day 1 up to Weeks 24 and 48
Population: FAS included all participants who had taken at least 1 dose of rilpivirine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48 | Week 24: <50 copies/mL | 100.0 Percentage of participants |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48 | Week 24: >=50 copies/mL | 0.0 Percentage of participants |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48 | Week 48: <50 copies/mL | 100.0 Percentage of participants |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48 | Week 48: >=50 copies/mL | 0.0 Percentage of participants |
| Rilpivirine: >=6 to <12 Years | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48 | Week 48: >=50 copies/mL | 0.0 Percentage of participants |
| Rilpivirine: >=6 to <12 Years | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48 | Week 24: <50 copies/mL | 100.0 Percentage of participants |
| Rilpivirine: >=6 to <12 Years | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48 | Week 48: <50 copies/mL | 100.0 Percentage of participants |
| Rilpivirine: >=6 to <12 Years | Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 and >=50 Copies/mL Through Weeks 24 and 48 | Week 24: >=50 copies/mL | 0.0 Percentage of participants |
Secondary
Percentage of Participants With Treatment Adherence >95% Based on Tablet Count up to Weeks 24 and 48
Percentage of participants with treatment adherence greater than (\>) 95 percent (%) as assessed by tablet count (study intervention accountability) up to Weeks 24 and 48 of study treatment were reported. Treatment adherence was defined as having a treatment adherence of \>95% by tablet count.
Time frame: From Day 1 up to Weeks 24 and 48
Population: FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): participants who were evaluable for this outcome measure. For participants who never returned kits dispensed at baseline, adherence could not be derived.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Percentage of Participants With Treatment Adherence >95% Based on Tablet Count up to Weeks 24 and 48 | Week 48 | 100.0 Percentage of participants |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Percentage of Participants With Treatment Adherence >95% Based on Tablet Count up to Weeks 24 and 48 | Week 24 | 100.0 Percentage of participants |
| Rilpivirine: >=6 to <12 Years | Percentage of Participants With Treatment Adherence >95% Based on Tablet Count up to Weeks 24 and 48 | Week 24 | 86.4 Percentage of participants |
| Rilpivirine: >=6 to <12 Years | Percentage of Participants With Treatment Adherence >95% Based on Tablet Count up to Weeks 24 and 48 | Week 48 | 90.9 Percentage of participants |
Secondary
Percentage of Participants With Viral Genotype at the Time of Virologic Failure at Weeks 24 and 48
Percentage of participants with viral genotype at the time of virologic failure (that is, HIV 1 RNA \>=50 copies/mL and \>=400 copies/mL) per FDA snapshot approach were reported. Confirmed virologic failure was defined as 2 consecutive HIV-1 RNA plasma viral load measurements \>=200 copies/mL and suspected virologic failure was defined as HIV-1 RNA \>=200 copies/mL. No participant achieved virologic failure hence this outcome measure could not be evaluated.
Time frame: Weeks 24 and 48
Population: FAS included all participants who had taken at least 1 dose of rilpivirine.
| Arm | Measure | Group | Value |
|---|---|---|---|
| Unknown | Percentage of Participants With Viral Genotype at the Time of Virologic Failure at Weeks 24 and 48 | Week 24 | — |
| Unknown | Percentage of Participants With Viral Genotype at the Time of Virologic Failure at Weeks 24 and 48 | Week 48 | — |
Secondary
Predose Plasma Concentration (C[0h]) of Rilpivirine 12.5 mg (for <20 kg Group)
C(0h) was defined as the predose plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. Out of the 2 participants weighing \<20 kg who received rilpivirine 15 mg, 1 participant switched to rilpivirine 12.5 mg group after the first 4 weeks. This participant was counted in the \<20 kg rilpivirine 12.5 mg group for the pharmacokinetic assessments, hence the number of participants analyzed for this outcome measure in this arm are exceeding the participants that started this arm. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Predose Plasma Concentration (C[0h]) of Rilpivirine 12.5 mg (for <20 kg Group) | Participant 1 | 116 ng/mL |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Predose Plasma Concentration (C[0h]) of Rilpivirine 12.5 mg (for <20 kg Group) | Participant 2 | 161 ng/mL |
Secondary
Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for <20 kg Group)
C(0h) was defined as the predose plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for <20 kg Group) | 79.3 ng/mL |
Secondary
Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for 20 to <25 kg Group)
C(0h) was defined as the predose plasma concentration of rilpivirine. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Predose Plasma Concentration (C[0h]) of Rilpivirine 15 mg (for 20 to <25 kg Group) | 138 ng/mL | Standard Deviation 58.7 |
Secondary
Predose Plasma Concentration (C[0h]) of Rilpivirine 25 mg (for >=25 kg Group)
C(0h) was defined as the predose plasma concentration of rilpivirine. As planned, data was not summarized for arms where number of participants analyzed was less than 3. Only individual participant data was available and reported in this outcome measure. As per protocol, the intensive PK samples were collected at anytime during Day 28 to Day 32 after first dose at the specified dose regimen.
Time frame: Predose at anytime during Day 28 to Day 32 (Week 4)
Population: FAS included all participants who had taken at least 1 dose of rilpivirine. N (number of participants analyzed): who were evaluable for this outcome measure, intensive PK data was collected from a subset of participants.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Predose Plasma Concentration (C[0h]) of Rilpivirine 25 mg (for >=25 kg Group) | Participant 1 | 146 ng/mL |
| Rilpivirine 12.5 Milligrams (mg) (<20 kg) | Predose Plasma Concentration (C[0h]) of Rilpivirine 25 mg (for >=25 kg Group) | Participant 2 | 342 ng/mL |