Acquired Immune Deficiency Syndrome (AIDS), HIV Infections
Conditions
Keywords
Pediatrics, Adolescents, HIV, HIV-1, Treatment-experienced
Brief summary
The primary objectives of this study are to evaluate the safety, tolerability and steady-state PK and confirm the dose of EVG/r in HIV-1 infected, antiretroviral treatment-experienced children 4 weeks to \<18 years of age. The study consists of 2 parts: Part A and Part B. Part A will enroll participants with suppressed viremia (HIV-1 RNA \< 50 copies/mL) or failing a current antiretroviral (ARV) regimen (HIV-1 RNA \> 1,000 copies/mL only for participants in Cohort 2, Part A) to evaluate the steady state PK and confirm the dose of EVG. Part B will enroll participants who are failing a current ARV regimen (HIV-1 RNA \> 1,000 copies/mL) to evaluate the safety, tolerability, and antiviral activity of EVG. The study consists of 4 age cohorts with each cohort including 2 parts (Part A and Part B) with the exception of the adolescent age cohort (Cohort 1: 12 to \< 18 years old) containing Part B only.
Interventions
DRUGEVG
Tablet (s) or tablet (s) for oral suspension (if unable to swallow) will be administered orally once daily
Background regimen may consist of the following ritonavir (RTV)-boosted PIs (PI/r): lopinavir/r (Kaletra), atazanavir/r, darunavir/r, tipranavir/r, or fosamprenavir/r. For participants \< 2 months old, only lopinavir/r is allowed. Use of additional antiretrovirals in background therapy may be allowed.
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Weeks to 17 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Individuals must meet all of the following inclusion criteria to be eligible for participation in this study. Individuals with screening results that do not meet eligibility criteria will not be allowed to rescreen. * HIV-1 infected male and female individuals 4 weeks (gestational age of at least 44 weeks) to less than 18 years of age at Baseline. * Individuals are able to provide written assent if they have the ability to read and write. * Parent or legal guardian able to provide written informed consent prior to any screening evaluations and willing to comply with study requirements. * Body weight at screening greater than 5kg, 10.6kg, or 15kg dependent upon age cohort * Adequate renal function * Adequate hematologic function * Hepatic transaminases (AST and ALT) less than or equal to 5 x upper limit of normal (ULN) * Total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin * Negative serum pregnancy test * Individuals with evidence of suppressed viremia * Individuals failing a current antiretroviral regimen at study entry * Male and female individuals of childbearing potential must agree to utilize highly effective contraception methods while on study treatment or agree to abstain from heterosexual intercourse of reproductive potential throughout the study period and for 30 days following the last dose of study drug * Must be willing and able to comply with all study requirements. Key
Exclusion criteria
Participants who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter: AUCtau of EVG | Predose and up to 12 hours postdose on Day 10 | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
| Pharmacokinetic (PK) Parameter: Cmax of EVG at Day 10 | Predose and up to 12 hours postdose on Day 10 | Cmax is defined as the maximum concentration of drug. |
| Percentage of Participants Experiencing Treatment-emergent Adverse Events | Baseline up to the last dose date plus 30 days (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years Screening HIV-1 RNA < 50 copies/mL) | — |
| Percentage of Participants Experiencing Laboratory Abnormalities | Baseline up to the last dose date plus 30 days (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years Screening HIV-1 RNA < 50 copies/mL) | Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each subject. The criteria used to grade laboratory results were as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (life-threatening). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm | Week 48 | The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. |
| Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm | Week 24 | The percentage of participants achieving HIV-1 RNA \< 400 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. |
| Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm | Week 48 | The percentage of participants achieving HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. |
| Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 24 | Baseline to Week 24 | — |
| Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 48 | Baseline to Week 48 | — |
| Change From Baseline in CD4 Cell Count at Week 24 | Baseline to Week 24 | — |
| Change From Baseline in CD4 Cell Count at Week 48 | Baseline to Week 48 | — |
| Pharmacokinetic (PK) Parameter: Ctau of EVG | Predose and up to 12 hours postdose on Day 10 | Ctau is defined as the observed drug concentration at the end of the dosing interval. |
| Change From Baseline in CD4 Percentage at Week 48 | Baseline to Week 48 | — |
| Tanner Stage Evaluation by Sex at Week 24 | Week 24 | Tanner Stage (pubic hair and breasts for females; pubic hair and genitalia for males) at Week 24 visit was summarized using frequency count and percentage. Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). |
| Tanner Stage Evaluation by Sex at Week 48 | Week 48 | Tanner Stage (pubic hair and breasts for females; pubic hair and genitalia for males) at Week 48 visit was summarized using frequency count and percentage. Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics). |
| Age of First Menses | Baseline through end of study (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years with Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years with Screening HIV-1 RNA < 50 copies/mL) | Age of first menses for female participants. |
| Palatability of Oral Suspension Formulation of EVG in Appropriate Age Group | Up to Week 48 | — |
| Adherence to EVG | Baseline up to the last dose date (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years Screening HIV-1 RNA < 50 copies/mL) | Adherence was calculated as the number of pills taken divided by number of pills prescribed multiplied by 100. |
| Change From Baseline in CD4 Percentage at Week 24 | Baseline to Week 24 | — |
| Pharmacokinetic (PK) Parameter: CL/F of EVG | Predose and up to 12 hours postdose on Day 10 | CL/F is defined as the apparent oral clearance following administration of the drug. |
| Pharmacokinetic (PK) Parameter: Vz/F of EVG | Predose and up to 12 hours postdose on Day 10 | Vz/F is defined as the apparent volume of distribution of the drug. |
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm | Week 24 | The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. |
Countries
Italy, South Africa, Spain, Thailand, Uganda, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in North America, Europe, Asia, and Africa. The first participant was screened on 26 August 2013. The last study visit occurred on 03 November 2017.
Pre-assignment details
48 participants were screened. The study was discontinued after enrollment of only Cohort 1, Part B and Cohort 2, Part A. The study close-out was triggered by the voluntary withdrawal of single-agent Vitekta® sale based solely on low utilization of the product, and was not a result of any ongoing or new safety issue.
Participants by arm
| Arm | Count |
|---|---|
| Age 6 to < 18 Years With Screening HIV-1 RNA > 1000 Copies/mL EVG 50 mg, or 85 mg, or 150 mg tablet administered QD for at least 48 weeks with the option to continue receiving EVG after Week 48 in the extension phase, based on body weight and dependent on the coadministered background regimen. (Background regimen may consist of the following PI/r: LPV/r, ATV/r, DRV/r, TPV/r, or FPV/r. Use of additional antiretrovirals in background therapy was allowed.). After Week 48, participants were given the opportunity to continue receiving EVG in an extension phase, during which they attended study visits every 12 weeks, until they reached 18 years of age and EVG was commercially available for use in adults in the country in which they were enrolled; the age-appropriate EVG formulation became commercially available in the country in which they were enrolled; or Gilead elected to terminate the development of EVG. | 17 |
| Age 6 to < 12 Years With Screening HIV-1 RNA < 50 Copies/mL EVG 50 mg, or 85 mg tablet administered QD for 10 days, based on body weight and dependent on the coadministered background regimen. (Background regimen may consist of the following PI/r: LPV/r, ATV/r, DRV/r, TPV/r, or FPV/r. Use of additional antiretrovirals in background therapy was allowed.) | 14 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator's Discretion | 1 | 0 |
| Overall Study | Non-Compliance with Study Drug | 2 | 1 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Study Terminated by Sponsor | 12 | 0 |
| Overall Study | Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Age 6 to < 18 Years With Screening HIV-1 RNA > 1000 Copies/mL | Age 6 to < 12 Years With Screening HIV-1 RNA < 50 Copies/mL |
|---|---|---|---|
| Age, Continuous | 12 years STANDARD_DEVIATION 3.8 | 14 years STANDARD_DEVIATION 2.9 | 9 years STANDARD_DEVIATION 2.2 |
| Age, Customized Age 12 to < 18 Years | 15 Participants | 15 Participants | 0 Participants |
| Age, Customized Age 6 to < 12 Years | 16 Participants | 2 Participants | 14 Participants |
| Cluster of differentiation (CD4) Cell Count | 561.7 cells/uL STANDARD_DEVIATION 354.74 | 356.6 cells/uL STANDARD_DEVIATION 249.45 | 810.8 cells/uL STANDARD_DEVIATION 303.29 |
| Cluster of differentiation (CD4) Cell Count Category ≥ 200 to < 350 cells/uL | 3 Participants | 3 Participants | 0 Participants |
| Cluster of differentiation (CD4) Cell Count Category ≥ 350 to < 500 cells/uL | 4 Participants | 4 Participants | 0 Participants |
| Cluster of differentiation (CD4) Cell Count Category ≥ 500 cells/uL | 17 Participants | 4 Participants | 13 Participants |
| Cluster of differentiation (CD4) Cell Count Category < 50 cells/uL | 0 Participants | 0 Participants | 0 Participants |
| Cluster of differentiation (CD4) Cell Count Category ≥ 50 to < 200 cells/uL | 7 Participants | 6 Participants | 1 Participants |
| Cluster of differentiation (CD4) Percentage | 25.8 percentage (%) STANDARD_DEVIATION 12.85 | 17.8 percentage (%) STANDARD_DEVIATION 9.6 | 35.5 percentage (%) STANDARD_DEVIATION 9.11 |
| HIV-1 RNA | 2.91 log10 copies/mL STANDARD_DEVIATION 1.576 | 4.21 log10 copies/mL STANDARD_DEVIATION 0.802 | 1.33 log10 copies/mL STANDARD_DEVIATION 0.204 |
| HIV-1 RNA Category > 100000 copies/mL | 1 Participants | 1 Participants | 0 Participants |
| HIV-1 RNA Category > 1000 to ≤ 100000 copies/mL | 13 Participants | 13 Participants | 0 Participants |
| HIV-1 RNA Category < 50 copies/mL | 13 Participants | 0 Participants | 13 Participants |
| HIV-1 RNA Category ≥ 50 to ≤ 1000 copies/mL | 4 Participants | 3 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 7 Participants | 5 Participants | 2 Participants |
| Race/Ethnicity, Customized Black | 21 Participants | 11 Participants | 10 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 30 Participants | 17 Participants | 13 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Italy | 1 Participants | 1 Participants | 0 Participants |
| Region of Enrollment South Africa | 7 Participants | 7 Participants | 0 Participants |
| Region of Enrollment Spain | 2 Participants | 0 Participants | 2 Participants |
| Region of Enrollment Thailand | 7 Participants | 5 Participants | 2 Participants |
| Region of Enrollment Uganda | 6 Participants | 3 Participants | 3 Participants |
| Region of Enrollment United States | 8 Participants | 1 Participants | 7 Participants |
| Sex: Female, Male Female | 17 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Male | 14 Participants | 6 Participants | 8 Participants |
| Type of PI in Background Regimen (Excluding Ritonavir) atazanavir | 9 Participants | 8 Participants | 1 Participants |
| Type of PI in Background Regimen (Excluding Ritonavir) darunavir | 3 Participants | 3 Participants | 0 Participants |
| Type of PI in Background Regimen (Excluding Ritonavir) lopinavir | 19 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 14 |
| other Total, other adverse events | 17 / 17 | 5 / 14 |
| serious Total, serious adverse events | 2 / 17 | 1 / 14 |
Outcome results
Primary
Percentage of Participants Experiencing Laboratory Abnormalities
Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. The most severe graded abnormality from all tests was counted for each subject. The criteria used to grade laboratory results were as follows: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (life-threatening).
Time frame: Baseline up to the last dose date plus 30 days (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years Screening HIV-1 RNA < 50 copies/mL)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Age 6 to < 12 Years | Percentage of Participants Experiencing Laboratory Abnormalities | Grade 1 | 11.8 percentage of participants |
| Age 6 to < 12 Years | Percentage of Participants Experiencing Laboratory Abnormalities | Grade 2 | 35.3 percentage of participants |
| Age 6 to < 12 Years | Percentage of Participants Experiencing Laboratory Abnormalities | Grade 3 | 35.3 percentage of participants |
| Age 6 to < 12 Years | Percentage of Participants Experiencing Laboratory Abnormalities | Grade 4 | 17.6 percentage of participants |
| Age 6 to < 12 Years With Screening HIV-1 RNA < 50 Copies/mL | Percentage of Participants Experiencing Laboratory Abnormalities | Grade 4 | 0 percentage of participants |
| Age 6 to < 12 Years With Screening HIV-1 RNA < 50 Copies/mL | Percentage of Participants Experiencing Laboratory Abnormalities | Grade 1 | 50.0 percentage of participants |
| Age 6 to < 12 Years With Screening HIV-1 RNA < 50 Copies/mL | Percentage of Participants Experiencing Laboratory Abnormalities | Grade 3 | 7.1 percentage of participants |
| Age 6 to < 12 Years With Screening HIV-1 RNA < 50 Copies/mL | Percentage of Participants Experiencing Laboratory Abnormalities | Grade 2 | 21.4 percentage of participants |
Primary
Percentage of Participants Experiencing Treatment-emergent Adverse Events
Time frame: Baseline up to the last dose date plus 30 days (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years Screening HIV-1 RNA < 50 copies/mL)
Population: Safety Analysis Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Age 6 to < 12 Years | Percentage of Participants Experiencing Treatment-emergent Adverse Events | 100.0 percentage of participants |
| Age 6 to < 12 Years With Screening HIV-1 RNA < 50 Copies/mL | Percentage of Participants Experiencing Treatment-emergent Adverse Events | 35.7 percentage of participants |
Primary
Pharmacokinetic (PK) Parameter: AUCtau of EVG
AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).
Time frame: Predose and up to 12 hours postdose on Day 10
Population: Intensive PK Analysis Set(EVG): all enrolled participants who received at least 1 dose of study drug and for whom steady-state pharmacokinetic profiles of the analyte of interest at the Intensive PK(Day 10) visit were evaluable.Includes 12 participants with screening HIV-1 RNA\<50 copies/mL and 2 participants with screening HIV-1 RNA\>1000 copies/mL.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Pharmacokinetic (PK) Parameter: AUCtau of EVG | 24028.3 h*ng/mL | Standard Deviation 7302.44 |
Comparison: To determine whether the proposed EVG dose in children achieved similar systemic exposure to adults, statistical comparisons were performed with PK data from the current study (test) and adult data from population PK modeling in study GS-US-183-0145 (NCT00708162) (reference).90% CI: [116.24, 158.49]
Primary
Pharmacokinetic (PK) Parameter: Cmax of EVG at Day 10
Cmax is defined as the maximum concentration of drug.
Time frame: Predose and up to 12 hours postdose on Day 10
Population: Intensive PK Analysis Set (EVG)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Pharmacokinetic (PK) Parameter: Cmax of EVG at Day 10 | 2022.1 ng/mL | Standard Deviation 599.94 |
Comparison: To determine whether the proposed EVG dose in children achieves similar systemic exposure to adults, statistical comparisons were performed with PK data from the current study (test) and adult data from population PK modeling in study GS-US-183-0145 (NCT00708162) (reference).90% CI: [127.35, 168.94]
Secondary
Adherence to EVG
Adherence was calculated as the number of pills taken divided by number of pills prescribed multiplied by 100.
Time frame: Baseline up to the last dose date (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years Screening HIV-1 RNA < 50 copies/mL)
Population: Safety Analysis Set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Adherence to EVG | 91.1 percentage of pills | Standard Deviation 8.94 |
| Age 6 to < 12 Years With Screening HIV-1 RNA < 50 Copies/mL | Adherence to EVG | 100.0 percentage of pills | Standard Deviation 0 |
Secondary
Age of First Menses
Age of first menses for female participants.
Time frame: Baseline through end of study (maximum exposure: 173.6 weeks for participants age 6 to < 18 Years with Screening HIV-1 RNA > 1000 copies/mL and 2.0 weeks for participants age 6 to < 12 Years with Screening HIV-1 RNA < 50 copies/mL)
Population: Participants in the Safety Analysis Set with available data were analyzed. Age of First Menses for participants ages 6 to \< 12 years with screening HIV-1 RNA \< 50 copies/mL was not analyzed because none of the participants reached their first menstruation cycle during or prior to the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Age of First Menses | 13 years | Standard Deviation 1.9 |
Secondary
Change From Baseline in CD4 Cell Count at Week 24
Time frame: Baseline to Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. Week 24 CD4 Cell Count data for participants with screening HIV-1 RNA \< 50 copies/mL was not analyzed due to the short duration of treatment (10 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Change From Baseline in CD4 Cell Count at Week 24 | 77.6 cells/uL | Standard Deviation 138.06 |
Secondary
Change From Baseline in CD4 Cell Count at Week 48
Time frame: Baseline to Week 48
Population: Participants in the Full Analysis Set with available data were analyzed. Week 48 CD4 Cell Count data for participants with screening HIV-1 RNA \< 50 copies/mL was not analyzed due to the short duration of treatment (10 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Change From Baseline in CD4 Cell Count at Week 48 | 131.3 cells/uL | Standard Deviation 195.04 |
Secondary
Change From Baseline in CD4 Percentage at Week 24
Time frame: Baseline to Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. Week 24 CD4 percentage data for participants with screening HIV-1 RNA \< 50 copies/mL group was not analyzed due to the short duration of treatment (10 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Change From Baseline in CD4 Percentage at Week 24 | 3.56 percentage (%) | Standard Deviation 4.109 |
Secondary
Change From Baseline in CD4 Percentage at Week 48
Time frame: Baseline to Week 48
Population: Participants in the Full Analysis Set with available data were analyzed. Week 48 CD4 percentage data for participants with screening HIV-1 RNA \< 50 copies/mL group was not analyzed due to the short duration of treatment (10 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Change From Baseline in CD4 Percentage at Week 48 | 5.31 percentage (%) | Standard Deviation 5.772 |
Secondary
Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 24
Time frame: Baseline to Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. Week 24 Plasma Log₁₀ HIV-1 RNA data for participants with screening HIV-1 RNA \< 50 copies/mL was not analyzed due to the short duration of treatment (10 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 24 | -2.44 Log₁₀ copies/mL | Standard Deviation 1.132 |
Secondary
Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 48
Time frame: Baseline to Week 48
Population: Participants in the Full Analysis Set with available data were analyzed. Week 48 Plasma Log₁₀ HIV-1 RNA data for participants with screening HIV-1 RNA \< 50 copies/mL was not analyzed due to the short duration of treatment (10 days).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Change From Baseline in Plasma Log₁₀ HIV-1 RNA at Week 48 | -2.23 Log₁₀ copies/ mL | Standard Deviation 1.293 |
Secondary
Palatability of Oral Suspension Formulation of EVG in Appropriate Age Group
Time frame: Up to Week 48
Population: Palatability was only to be assessed for participants taking EVG suspension formulation. As no participants were dosed with the EVG oral suspension formulation, no data are available on its palatability.
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time frame: Week 24
Population: Full Analysis Set: all participants who were enrolled in the study and received at least 1 dose of study drug. Participants in the Full Analysis Set with available data were analyzed. Week 24 HIV-1 RNA copies for participants with screening HIV-1 RNA \< 50 copies/mL were not analyzed due to the short duration of treatment (10 days).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Age 6 to < 12 Years | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm | 76.5 percentage of participants |
Secondary
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time frame: Week 48
Population: Participants in the Full Analysis Set with available data were analyzed. Week 48 HIV-1 RNA copies for participants with screening HIV-1 RNA \< 50 copies/mL were not analyzed due to the short duration of treatment (10 days).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Age 6 to < 12 Years | Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm | 58.8 percentage of participants |
Secondary
Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm
The percentage of participants achieving HIV-1 RNA \< 400 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time frame: Week 24
Population: Participants in the Full Analysis Set with available data were analyzed. Week 24 HIV-1 RNA copies for participants with screening HIV-1 RNA \< 50 copies/mL were not analyzed due to the short duration of treatment (10 days).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Age 6 to < 12 Years | Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm | 82.4 percentage of participants |
Secondary
Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm
The percentage of participants achieving HIV-1 RNA \< 400 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
Time frame: Week 48
Population: Participants in the Full Analysis Set with available data were analyzed. Week 48 HIV-1 RNA copies for participants with screening HIV-1 RNA \< 50 copies/mL were not analyzed due to the short duration of treatment (10 days).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Age 6 to < 12 Years | Percentage of Participants With Plasma HIV-1 RNA < 400 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm | 76.5 percentage of participants |
Secondary
Pharmacokinetic (PK) Parameter: CL/F of EVG
CL/F is defined as the apparent oral clearance following administration of the drug.
Time frame: Predose and up to 12 hours postdose on Day 10
Population: Intensive PK Analysis set (EVG)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Pharmacokinetic (PK) Parameter: CL/F of EVG | 2863.5 mL/h | Standard Deviation 871.07 |
Secondary
Pharmacokinetic (PK) Parameter: Ctau of EVG
Ctau is defined as the observed drug concentration at the end of the dosing interval.
Time frame: Predose and up to 12 hours postdose on Day 10
Population: Intensive PK Analysis Set (EVG)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Pharmacokinetic (PK) Parameter: Ctau of EVG | 494.3 ng/mL | Standard Deviation 261.05 |
Secondary
Pharmacokinetic (PK) Parameter: Vz/F of EVG
Vz/F is defined as the apparent volume of distribution of the drug.
Time frame: Predose and up to 12 hours postdose on Day 10
Population: Participants in the Intensive PK Analysis Set: EVG with available data were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Age 6 to < 12 Years | Pharmacokinetic (PK) Parameter: Vz/F of EVG | 39508.3 mL | Standard Deviation 14071.51 |
Secondary
Tanner Stage Evaluation by Sex at Week 24
Tanner Stage (pubic hair and breasts for females; pubic hair and genitalia for males) at Week 24 visit was summarized using frequency count and percentage. Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics).
Time frame: Week 24
Population: Participants in the Safety Analysis Set with available data were analyzed. Tanner Stage Assessments were not defined for participants with screening HIV-1 RNA \< 50 copies/mL because there were no postbaseline assessments scheduled in the protocol for these participants.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Pubic Hair | Stage 1 | 1 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Pubic Hair | Stage 2 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Pubic Hair | Stage 3 | 4 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Pubic Hair | Stage 4 | 5 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Pubic Hair | Stage 5 | 1 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Pubic Hair | Missing | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Breasts | Stage 1 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Breasts | Stage 2 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Breasts | Stage 3 | 3 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Breasts | Stage 4 | 5 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Breasts | Stage 5 | 3 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Female: Breasts | Missing | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Pubic Hair | Stage 1 | 2 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Pubic Hair | Stage 2 | 2 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Pubic Hair | Stage 3 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Pubic Hair | Stage 4 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Pubic Hair | Stage 5 | 2 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Pubic Hair | Missing | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Genitalia | Stage 1 | 2 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Genitalia | Stage 2 | 2 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Genitalia | Stage 3 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Genitalia | Stage 4 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Genitalia | Stage 5 | 2 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 24 | Male: Genitalia | Missing | 0 Participants |
Secondary
Tanner Stage Evaluation by Sex at Week 48
Tanner Stage (pubic hair and breasts for females; pubic hair and genitalia for males) at Week 48 visit was summarized using frequency count and percentage. Tanner Stages is a scale that defines physical measurements of development based on external primary and secondary sex characteristics. It was used in this study to assess pubertal development with values ranging from Stage 1 (pre-pubertal characteristics) to Stage 5 (adult or mature characteristics).
Time frame: Week 48
Population: Participants in the Safety Analysis Set with available data were analyzed. Tanner Stage Assessments were not defined for participants with screening HIV-1 RNA \< 50 copies/mL because there were no postbaseline assessments scheduled in the protocol for these participants.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Pubic Hair | Stage 1 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Pubic Hair | Stage 2 | 1 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Pubic Hair | Stage 3 | 4 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Pubic Hair | Stage 4 | 4 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Pubic Hair | Stage 5 | 1 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Pubic Hair | Missing | 1 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Breasts | Stage 1 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Breasts | Stage 2 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Breasts | Stage 3 | 2 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Breasts | Stage 4 | 5 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Breasts | Stage 5 | 3 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Female: Breasts | Missing | 1 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Pubic Hair | Stage 1 | 3 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Pubic Hair | Stage 2 | 1 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Pubic Hair | Stage 3 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Pubic Hair | Stage 4 | 1 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Pubic Hair | Stage 5 | 1 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Pubic Hair | Missing | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Genitalia | Stage 1 | 2 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Genitalia | Stage 2 | 2 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Genitalia | Stage 3 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Genitalia | Stage 4 | 0 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Genitalia | Stage 5 | 2 Participants |
| Age 6 to < 12 Years | Tanner Stage Evaluation by Sex at Week 48 | Male: Genitalia | Missing | 0 Participants |