HIV Infections
Conditions
Brief summary
The primary objective is to establish the pharmacokinetic (PK) profile at steady state of nevirapine XR in HIV infected children from \>=3 to \<18 years of age. This phase I trial is an open-label, multiple dose, non-randomized and cross-over study. Patients who have completed the last visit of the PK trial (visit 7) can enter into an Optional Extension Phase (OEP) until the Investigational New Drug (IND) is withdrawn; until nevirapine XR becomes approved and is available by prescription in a given country; or, the patient enrolls in a compassionate use program. During this OEP, nevirapine XR safety and efficacy information will be collected.
Interventions
DRUGNevirapine Immediate Release (IR)
200 mg Tablet or 50 mg / 5 ml oral suspension
DRUGNevirapine Extended Release (XR)
200 mg, 300 mg or 400 mg Tablet formulation
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Signed and dated written informed consent of a parent or legal guardian prior to admission. Active assent must be given by the patient if the child and/or adolescent is capable of understanding the provided study information. 2. HIV-1 infected males or females \>= 3 and \< 18 years old. 3. BSA \>= 0.58 m2 for patients using BSA to calculate nevirapine IR dose; or BW \>= 12.5 kg for patients using BW to calculate nevirapine IR dose at screening visit. 4. Treated with a nevirapine IR based regimen for at least 18 weeks prior to screening visit (Visit 1); no modifications in the ARV background therapy within the last 2 weeks prior to screening. 5. An HIV VL of \<50 copies/mL while receiving nevirapine IR at the last measure of VL documented in the medical record obtained within a period of 5 months prior to screening visit. 6. An HIV VL of \<50 copies/mL at screening visit. 7. A stable or not decreasing CD4+ cell count according to the investigator's opinion. 8. Acceptable screening laboratory values that indicate adequate baseline organ function according to the opinion of investigator. 9. ALT and AST \<= 2.5 X ULN (DAIDS Grade 1). 10. Serum creatinine levels \<= 1.3 X ULN (DAIDS Grade 1). 11. Patients able to swallow tablets.
Exclusion criteria
1. Any AIDS-related or AIDS defining illness that is unresolved or not stable on treatment at least 8 weeks prior to screening visit. 2. Diseases other than HIV infection or conditions that, in the investigator's opinion, would interfere with the study. 3. Patients who have been diagnosed with malignant disease and who are receiving systemic chemotherapy or are anticipated to receive any therapy during their participation in this trial. 4. Use of investigational medications or vaccines within 28 days prior to Visit 1 or during the trial. 5. Use of immunomodulatory drugs within 28 days before Visit 1 or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2). 6. Concomitant protease inhibitor (PI) treatment. 7. Unwillingness to abstain from ingesting substances during the study which may alter plasma drug concentrations by interaction with the cytochrome P450 system (Appendix 10.2). 8. Female patients of childbearing potential who: * have a positive serum pregnancy test at screening, * are breast feeding, * are planning on becoming pregnant, * are not willing to use double-barrier methods
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Cpre,N. | Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR | Trough Nevirapine concentration immediately prior to the next scheduled dose. Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22. The measure of dispersion presented is the coefficient of variation (%) rather than the geometric coefficient of variation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUCt,ss | Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR | Area under the concentration-time curve of the Nevirapine (NVP) in plasma at steady state over the time dosing interval τ. All patients received nevirapine IR for 10 days prior to collection of 12-hour Area Under the Curve (AUC) data. Then, all patients were switched to nevirapine XR for 9 days prior to collection of 24-hour AUC data. The treatments of IR and XR are summarized separately using geometric means and geometric coefficients of variation. For NVP IR AUC measured over hours: 0,1,2,3,4,8 and 12, For NVP XR AUC measured over hours: 0,1,2,3,4,8,10,12 and 24. |
| Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR | Minimum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ by nevirapine XR dose group Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 21. |
| Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR | Maximum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22. |
| Ratio Cmax,ss/Cmin,ss | Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR | Ratio of (maximum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ)/(minimum measured concentration of the analyte in plasma at steady state over the time dosing interval τ) Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22. |
| %PTF | Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR | Percentage peak-trough Nevirapine fluctuation, % fluctuation (degree of peak to trough fluctuation) Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22. |
| Tmax,ss | Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR | Time from dosing to the maximum concentration of the Nevirapine in plasma at steady state over the time dosing interval τ Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22. The standard deviation is actually the coefficient of variation. |
| CL/F,ss | Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR | Apparent clearance of the Nevirapine in the plasma after extravascular administration at steady-state Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22. |
| Efficacy: Patients Maintaining a VL < 50 Copies/mL | Day 22 | Patients maintaining a viral load \< 50 copies/mL at Day 22. |
| Efficacy: Patients Maintaining a VL < 400 Copies/mL | Day 22 | Patients maintaining a viral load \< 400 copies/mL at Day 22 |
| Change From Baseline in Mean CD4+ Count (Absolute) | Baseline, Day 22 and week 24 | Change in mean CD4+ count (absolute) from baseline to Day 22 and from baseline to Week 24. |
| Percentage Change From Baseline in Mean CD4+ Count | Baseline to day 22 and baseline to week 24 | ((Day 22 value-Baseline value)/Baseline value)\*100. ((Week 24 value-Baseline value)/Baseline value)\*100. |
| Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase | week 24 | Patients maintaining a viral load \< 50 copies/mL at week 24 (approximately 168 days) of Optional Extension Phase (OEP). |
| Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase | week 24 | Patients maintaining a viral load \< 400 copies/mL at week 24 of the Optional Extension Phase (OEP) |
| Cavg | Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR | Average measured concentration of the Nevirapine in plasma at steady state Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Patients Maintaining a VL < 50 Copies/mL at Last Available Visit | Last available visit, up to 155 weeks | Patients maintaining a viral load \< 50 copies/mL at the last available visit |
Countries
Botswana, Germany, South Africa, United States
Participant flow
Recruitment details
Multicenter Phase I study in Botswana, Germany, South Africa and the United States.
Pre-assignment details
There was only one treatment group and no randomization process. Overall, 90 pediatric patients were enrolled. Five patients were not entered and 85 patients entered the study. Patients were stratified to the following three age groups: (26 in the 3 - \<6 year age group, 26 in the 6 - \< 12 year age group and 33 in the 12 - \< 18 year age group).
Participants by arm
| Arm | Count |
|---|---|
| Total. All patients enrolled in study.
All patients initially receive nevirapine immediate release (IR) and then all patients are switched to nevirapine extended release (XR) 100mg or 400mg tablets for a once daily dosing of 200 mg, 300 mg or 400 mg QD. After completing the PK phase patients had the option of continuing treatment with nevirapine XR in the Optional Extension Phase (OEP). | 85 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Optional Extension Phase (OEP) | Adverse Event | 1 |
| Pharmaco-kinetic (PK) Phase | Other reason not defined above | 3 |
| Pharmaco-kinetic (PK) Phase | Protocol Violation | 2 |
Baseline characteristics
| Characteristic | Total. |
|---|---|
| Age, Continuous | 9.3 years STANDARD_DEVIATION 4.6 |
| Sex: Female, Male Female | 47 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 56 / 85 |
| serious Total, serious adverse events | 3 / 85 |
Outcome results
Primary
Trough Cpre,N.
Trough Nevirapine concentration immediately prior to the next scheduled dose. Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22. The measure of dispersion presented is the coefficient of variation (%) rather than the geometric coefficient of variation.
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Population: PK analysis set (PKS): This patient set includes all patients in the Full Analysis Set (FAS) set that have no protocol violations excluding them from PK analyses.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| NVP XR | Trough Cpre,N. | 15.47 (ng/mL/mg) | Geometric Coefficient of Variation 64.34 |
| NVP IR | Trough Cpre,N. | 16.66 (ng/mL/mg) | Geometric Coefficient of Variation 75.03 |
p-value: 0.00890% CI: [83.47, 99.64]Mixed Models Analysis
Secondary
AUCt,ss
Area under the concentration-time curve of the Nevirapine (NVP) in plasma at steady state over the time dosing interval τ. All patients received nevirapine IR for 10 days prior to collection of 12-hour Area Under the Curve (AUC) data. Then, all patients were switched to nevirapine XR for 9 days prior to collection of 24-hour AUC data. The treatments of IR and XR are summarized separately using geometric means and geometric coefficients of variation. For NVP IR AUC measured over hours: 0,1,2,3,4,8 and 12, For NVP XR AUC measured over hours: 0,1,2,3,4,8,10,12 and 24.
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Population: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NVP XR | AUCt,ss | 200mg NVP XR QD (175-249 mg IR/day), n=23/22 | 99300 ng*h/ml | Geometric Coefficient of Variation 37.7 |
| NVP XR | AUCt,ss | 300mg NVP XR QD (250-349 mg IR/day), n=11/12 | 144000 ng*h/ml | Geometric Coefficient of Variation 50.1 |
| NVP XR | AUCt,ss | 400mg NVP XR QD (≥350 mg IR/day), n=11/15 | 108000 ng*h/ml | Geometric Coefficient of Variation 60.7 |
| NVP IR | AUCt,ss | 200mg NVP XR QD (175-249 mg IR/day), n=23/22 | 57900 ng*h/ml | Geometric Coefficient of Variation 45.7 |
| NVP IR | AUCt,ss | 300mg NVP XR QD (250-349 mg IR/day), n=11/12 | 58100 ng*h/ml | Geometric Coefficient of Variation 35 |
| NVP IR | AUCt,ss | 400mg NVP XR QD (≥350 mg IR/day), n=11/15 | 73400 ng*h/ml | Geometric Coefficient of Variation 39.8 |
Secondary
Cavg
Average measured concentration of the Nevirapine in plasma at steady state Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Population: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NVP XR | Cavg | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 4140 ng/mL | Geometric Coefficient of Variation 37.7 |
| NVP XR | Cavg | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 6010 ng/mL | Geometric Coefficient of Variation 50.1 |
| NVP XR | Cavg | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 4510 ng/mL | Geometric Coefficient of Variation 60.7 |
| NVP IR | Cavg | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 4820 ng/mL | Geometric Coefficient of Variation 45.7 |
| NVP IR | Cavg | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 4840 ng/mL | Geometric Coefficient of Variation 35 |
| NVP IR | Cavg | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 6120 ng/mL | Geometric Coefficient of Variation 39.8 |
Secondary
Change From Baseline in Mean CD4+ Count (Absolute)
Change in mean CD4+ count (absolute) from baseline to Day 22 and from baseline to Week 24.
Time frame: Baseline, Day 22 and week 24
Population: PK Analysis set: This patient set includes all patients in the Full Analysis Set (FAS) that have no protocol violations excluding them from PK analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NVP XR | Change From Baseline in Mean CD4+ Count (Absolute) | Day 22 | -115.6 cells/mm^3 | Standard Deviation 320.5 |
| NVP XR | Change From Baseline in Mean CD4+ Count (Absolute) | Week 24 (n=8;10;9) | -214.5 cells/mm^3 | Standard Deviation 397.5 |
| NVP IR | Change From Baseline in Mean CD4+ Count (Absolute) | Day 22 | 24.2 cells/mm^3 | Standard Deviation 184.8 |
| NVP IR | Change From Baseline in Mean CD4+ Count (Absolute) | Week 24 (n=8;10;9) | -51.2 cells/mm^3 | Standard Deviation 179.4 |
| 12-<18 yr | Change From Baseline in Mean CD4+ Count (Absolute) | Day 22 | 60.3 cells/mm^3 | Standard Deviation 171.2 |
| 12-<18 yr | Change From Baseline in Mean CD4+ Count (Absolute) | Week 24 (n=8;10;9) | 31.1 cells/mm^3 | Standard Deviation 66.4 |
Secondary
CL/F,ss
Apparent clearance of the Nevirapine in the plasma after extravascular administration at steady-state Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Population: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NVP XR | CL/F,ss | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 2010 mL/h | Geometric Coefficient of Variation 37.7 |
| NVP XR | CL/F,ss | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 2080 mL/h | Geometric Coefficient of Variation 50.1 |
| NVP XR | CL/F,ss | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 3700 mL/h | Geometric Coefficient of Variation 60.7 |
| NVP IR | CL/F,ss | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 1780 mL/h | Geometric Coefficient of Variation 44.3 |
| NVP IR | CL/F,ss | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 2240 mL/h | Geometric Coefficient of Variation 32.9 |
| NVP IR | CL/F,ss | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 2640 mL/h | Geometric Coefficient of Variation 39.3 |
Secondary
Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group)
Maximum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Population: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NVP XR | Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 5350 ng/mL | Geometric Coefficient of Variation 43.1 |
| NVP XR | Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 7970 ng/mL | Geometric Coefficient of Variation 53.5 |
| NVP XR | Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 5890 ng/mL | Geometric Coefficient of Variation 50.5 |
| NVP IR | Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 6850 ng/mL | Geometric Coefficient of Variation 52.6 |
| NVP IR | Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 6580 ng/mL | Geometric Coefficient of Variation 31.4 |
| NVP IR | Cmax,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 7790 ng/mL | Geometric Coefficient of Variation 43.2 |
Secondary
Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group)
Minimum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ by nevirapine XR dose group Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 21.
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Population: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NVP XR | Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 3090 ng/mL | Geometric Coefficient of Variation 37.9 |
| NVP XR | Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 4160 ng/mL | Geometric Coefficient of Variation 62.6 |
| NVP XR | Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 3410 ng/mL | Geometric Coefficient of Variation 63 |
| NVP IR | Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 3280 ng/mL | Geometric Coefficient of Variation 57.6 |
| NVP IR | Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 3620 ng/mL | Geometric Coefficient of Variation 34.7 |
| NVP IR | Cmin,ss (for IR and XR Formulations by Nevirapine XR Dose Group) | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 4960 ng/mL | Geometric Coefficient of Variation 39.1 |
Secondary
Efficacy: Patients Maintaining a VL < 400 Copies/mL
Patients maintaining a viral load \< 400 copies/mL at Day 22
Time frame: Day 22
Population: Full analysis set including patients with available viral load data at day 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVP XR | Efficacy: Patients Maintaining a VL < 400 Copies/mL | 100.0 percentage of patients |
| NVP IR | Efficacy: Patients Maintaining a VL < 400 Copies/mL | 100.0 percentage of patients |
| 12-<18 yr | Efficacy: Patients Maintaining a VL < 400 Copies/mL | 100.0 percentage of patients |
| Total. | Efficacy: Patients Maintaining a VL < 400 Copies/mL | 100.0 percentage of patients |
Secondary
Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase
Patients maintaining a viral load \< 400 copies/mL at week 24 of the Optional Extension Phase (OEP)
Time frame: week 24
Population: Full analysis set including patients with available viral load data at week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVP XR | Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase | 100.0 percentage of patients |
| NVP IR | Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase | 100.0 percentage of patients |
| 12-<18 yr | Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase | 100.0 percentage of patients |
| Total. | Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase | 100.0 percentage of patients |
Secondary
Efficacy: Patients Maintaining a VL < 50 Copies/mL
Patients maintaining a viral load \< 50 copies/mL at Day 22.
Time frame: Day 22
Population: Full analysis set including patients with available viral load data at day 22
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVP XR | Efficacy: Patients Maintaining a VL < 50 Copies/mL | 96.0 percentage of patients |
| NVP IR | Efficacy: Patients Maintaining a VL < 50 Copies/mL | 100.0 percentage of patients |
| 12-<18 yr | Efficacy: Patients Maintaining a VL < 50 Copies/mL | 100.0 percentage of patients |
| Total. | Efficacy: Patients Maintaining a VL < 50 Copies/mL | 98.7 percentage of patients |
Secondary
Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase
Patients maintaining a viral load \< 50 copies/mL at week 24 (approximately 168 days) of Optional Extension Phase (OEP).
Time frame: week 24
Population: Full analysis set including patients with available viral load data at week 24
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVP XR | Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase | 100.0 percentage of patients |
| NVP IR | Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase | 100.0 percentage of patients |
| 12-<18 yr | Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase | 100.0 percentage of patients |
| Total. | Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase | 100.0 percentage of patients |
Secondary
Percentage Change From Baseline in Mean CD4+ Count
((Day 22 value-Baseline value)/Baseline value)\*100. ((Week 24 value-Baseline value)/Baseline value)\*100.
Time frame: Baseline to day 22 and baseline to week 24
Population: Optional Extension Phase Treated Set (OEP TS), all patients that complete PK phase and enroll in Extension phase, and had available data at either day 22 or week 24.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NVP XR | Percentage Change From Baseline in Mean CD4+ Count | Day 22 | -2.1 percentage change | Standard Deviation 6.7 |
| NVP XR | Percentage Change From Baseline in Mean CD4+ Count | Week 24 (n=8, 10, 9) | -2.1 percentage change | Standard Deviation 4 |
| NVP IR | Percentage Change From Baseline in Mean CD4+ Count | Day 22 | -0.0 percentage change | Standard Deviation 2.5 |
| NVP IR | Percentage Change From Baseline in Mean CD4+ Count | Week 24 (n=8, 10, 9) | -2.1 percentage change | Standard Deviation 3.4 |
| 12-<18 yr | Percentage Change From Baseline in Mean CD4+ Count | Day 22 | 0.5 percentage change | Standard Deviation 3.6 |
| 12-<18 yr | Percentage Change From Baseline in Mean CD4+ Count | Week 24 (n=8, 10, 9) | -1.0 percentage change | Standard Deviation 2.9 |
Secondary
%PTF
Percentage peak-trough Nevirapine fluctuation, % fluctuation (degree of peak to trough fluctuation) Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Population: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NVP XR | %PTF | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 49.7 percentage fluctuation | Geometric Coefficient of Variation 47.3 |
| NVP XR | %PTF | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 54.6 percentage fluctuation | Geometric Coefficient of Variation 61.1 |
| NVP XR | %PTF | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 51.0 percentage fluctuation | Geometric Coefficient of Variation 47.6 |
| NVP IR | %PTF | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 67.9 percentage fluctuation | Geometric Coefficient of Variation 49.8 |
| NVP IR | %PTF | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 59.1 percentage fluctuation | Geometric Coefficient of Variation 29.4 |
| NVP IR | %PTF | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 41.5 percentage fluctuation | Geometric Coefficient of Variation 55.7 |
Secondary
Ratio Cmax,ss/Cmin,ss
Ratio of (maximum measured concentration of the Nevirapine in plasma at steady state over the time dosing interval τ)/(minimum measured concentration of the analyte in plasma at steady state over the time dosing interval τ) Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22.
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Population: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| NVP XR | Ratio Cmax,ss/Cmin,ss | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 1.73 Ratio | Geometric Coefficient of Variation 23.7 |
| NVP XR | Ratio Cmax,ss/Cmin,ss | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 1.91 Ratio | Geometric Coefficient of Variation 39.4 |
| NVP XR | Ratio Cmax,ss/Cmin,ss | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 1.73 Ratio | Geometric Coefficient of Variation 21.8 |
| NVP IR | Ratio Cmax,ss/Cmin,ss | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 2.09 Ratio | Geometric Coefficient of Variation 32.3 |
| NVP IR | Ratio Cmax,ss/Cmin,ss | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 1.82 Ratio | Geometric Coefficient of Variation 17.8 |
| NVP IR | Ratio Cmax,ss/Cmin,ss | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 1.57 Ratio | Geometric Coefficient of Variation 21.1 |
Secondary
Tmax,ss
Time from dosing to the maximum concentration of the Nevirapine in plasma at steady state over the time dosing interval τ Patients took Nevirapine (NVP) Immediate Release (IR) up to day 10 and had PK measurements taken on Day 11. This was followed by 9 days (from day 12 to day 20) taking NVP Extended Release (XR) with PK measurements taken on Day 22. The standard deviation is actually the coefficient of variation.
Time frame: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
Population: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NVP XR | Tmax,ss | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 6.34 hours | Standard Deviation 104 |
| NVP XR | Tmax,ss | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 7.28 hours | Standard Deviation 121 |
| NVP XR | Tmax,ss | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 5.73 hours | Standard Deviation 129 |
| NVP IR | Tmax,ss | 200 mg XR QD (175-249 mg IR/day), n=23,22 | 2.46 hours | Standard Deviation 57.9 |
| NVP IR | Tmax,ss | 300 mg XR QD (250-349 mg IR/day), n=11,12 | 2.49 hours | Standard Deviation 50.4 |
| NVP IR | Tmax,ss | 400 mg XR QD (≥350 mg IR/day), n=11,15 | 4.41 hours | Standard Deviation 94.2 |
Other Pre-specified
Efficacy: Patients Maintaining a VL < 50 Copies/mL at Last Available Visit
Patients maintaining a viral load \< 50 copies/mL at the last available visit
Time frame: Last available visit, up to 155 weeks
Population: Optional Extension Phase Treated Set (OEP TS), all patients that complete PK phase and enroll in Extension phase with VL data available
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| NVP XR | Efficacy: Patients Maintaining a VL < 50 Copies/mL at Last Available Visit | 100.0 percentage of patients |
| NVP IR | Efficacy: Patients Maintaining a VL < 50 Copies/mL at Last Available Visit | 100.0 percentage of patients |
| 12-<18 yr | Efficacy: Patients Maintaining a VL < 50 Copies/mL at Last Available Visit | 100.0 percentage of patients |
| Total. | Efficacy: Patients Maintaining a VL < 50 Copies/mL at Last Available Visit | 100.0 percentage of patients |