Trial Outcomes & Findings for A Phase I Multiple Dose Pharmacokinetic Study of Nevirapine Extended Release (XR) in HIV-1 Infected Children. (NCT NCT00905489)
NCT ID: NCT00905489
Last Updated: 2016-01-07
Results Overview
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.
COMPLETED
PHASE1
85 participants
Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XR
2016-01-07
Participant Flow
Multicenter Phase I study in Botswana, Germany, South Africa and the United States.
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).
Participant milestones
| Measure |
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).
|
|---|---|
|
Pharmaco-kinetic (PK) Phase
STARTED
|
85
|
|
Pharmaco-kinetic (PK) Phase
COMPLETED
|
80
|
|
Pharmaco-kinetic (PK) Phase
NOT COMPLETED
|
5
|
|
Optional Extension Phase (OEP)
STARTED
|
40
|
|
Optional Extension Phase (OEP)
COMPLETED
|
39
|
|
Optional Extension Phase (OEP)
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
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).
|
|---|---|
|
Pharmaco-kinetic (PK) Phase
Protocol Violation
|
2
|
|
Pharmaco-kinetic (PK) Phase
Other reason not defined above
|
3
|
|
Optional Extension Phase (OEP)
Adverse Event
|
1
|
Baseline Characteristics
A Phase I Multiple Dose Pharmacokinetic Study of Nevirapine Extended Release (XR) in HIV-1 Infected Children.
Baseline characteristics by cohort
| Measure |
Total.
n=85 Participants
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).
|
|---|---|
|
Age, Continuous
|
9.3 years
STANDARD_DEVIATION 4.6 • n=39 Participants
|
|
Sex: Female, Male
Female
|
47 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XRPopulation: 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.
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.
Outcome measures
| Measure |
NVP XR
n=74 Participants
Nevirapine XR (extended release)
|
NVP IR
n=78 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
Trough Cpre,N.
|
15.47 (ng/mL/mg)
Geometric Coefficient of Variation 64.34
|
16.66 (ng/mL/mg)
Geometric Coefficient of Variation 75.03
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XRPopulation: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
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.
Outcome measures
| Measure |
NVP XR
n=45 Participants
Nevirapine XR (extended release)
|
NVP IR
n=49 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
AUCt,ss
400mg NVP XR QD (≥350 mg IR/day), n=11/15
|
108000 ng*h/ml
Geometric Coefficient of Variation 60.7
|
73400 ng*h/ml
Geometric Coefficient of Variation 39.8
|
—
|
—
|
|
AUCt,ss
200mg NVP XR QD (175-249 mg IR/day), n=23/22
|
99300 ng*h/ml
Geometric Coefficient of Variation 37.7
|
57900 ng*h/ml
Geometric Coefficient of Variation 45.7
|
—
|
—
|
|
AUCt,ss
300mg NVP XR QD (250-349 mg IR/day), n=11/12
|
144000 ng*h/ml
Geometric Coefficient of Variation 50.1
|
58100 ng*h/ml
Geometric Coefficient of Variation 35.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XRPopulation: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
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.
Outcome measures
| Measure |
NVP XR
n=45 Participants
Nevirapine XR (extended release)
|
NVP IR
n=49 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
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
|
3280 ng/mL
Geometric Coefficient of Variation 57.6
|
—
|
—
|
|
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
|
3620 ng/mL
Geometric Coefficient of Variation 34.7
|
—
|
—
|
|
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 63.0
|
4960 ng/mL
Geometric Coefficient of Variation 39.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XRPopulation: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
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.
Outcome measures
| Measure |
NVP XR
n=45 Participants
Nevirapine XR (extended release)
|
NVP IR
n=49 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
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
|
6850 ng/mL
Geometric Coefficient of Variation 52.6
|
—
|
—
|
|
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
|
6580 ng/mL
Geometric Coefficient of Variation 31.4
|
—
|
—
|
|
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
|
7790 ng/mL
Geometric Coefficient of Variation 43.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XRPopulation: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
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.
Outcome measures
| Measure |
NVP XR
n=45 Participants
Nevirapine XR (extended release)
|
NVP IR
n=49 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
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
|
2.09 Ratio
Geometric Coefficient of Variation 32.3
|
—
|
—
|
|
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
|
1.82 Ratio
Geometric Coefficient of Variation 17.8
|
—
|
—
|
|
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
|
1.57 Ratio
Geometric Coefficient of Variation 21.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XRPopulation: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
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.
Outcome measures
| Measure |
NVP XR
n=45 Participants
Nevirapine XR (extended release)
|
NVP IR
n=49 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
%PTF
200 mg XR QD (175-249 mg IR/day), n=23,22
|
49.7 percentage fluctuation
Geometric Coefficient of Variation 47.3
|
67.9 percentage fluctuation
Geometric Coefficient of Variation 49.8
|
—
|
—
|
|
%PTF
300 mg XR QD (250-349 mg IR/day), n=11,12
|
54.6 percentage fluctuation
Geometric Coefficient of Variation 61.1
|
59.1 percentage fluctuation
Geometric Coefficient of Variation 29.4
|
—
|
—
|
|
%PTF
400 mg XR QD (≥350 mg IR/day), n=11,15
|
51.0 percentage fluctuation
Geometric Coefficient of Variation 47.6
|
41.5 percentage fluctuation
Geometric Coefficient of Variation 55.7
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XRPopulation: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
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.
Outcome measures
| Measure |
NVP XR
n=45 Participants
Nevirapine XR (extended release)
|
NVP IR
n=49 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
Tmax,ss
400 mg XR QD (≥350 mg IR/day), n=11,15
|
5.73 hours
Standard Deviation 129 • Interval 0.0 to 24.0
|
4.41 hours
Standard Deviation 94.2 • Interval 0.0 to 12.0
|
—
|
—
|
|
Tmax,ss
200 mg XR QD (175-249 mg IR/day), n=23,22
|
6.34 hours
Standard Deviation 104 • Interval 1.8 to 24.0
|
2.46 hours
Standard Deviation 57.9 • Interval 0.0 to 7.4
|
—
|
—
|
|
Tmax,ss
300 mg XR QD (250-349 mg IR/day), n=11,12
|
7.28 hours
Standard Deviation 121 • Interval 0.0 to 24.0
|
2.49 hours
Standard Deviation 50.4 • Interval 0.0 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XRPopulation: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
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.
Outcome measures
| Measure |
NVP XR
n=45 Participants
Nevirapine XR (extended release)
|
NVP IR
n=49 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
CL/F,ss
200 mg XR QD (175-249 mg IR/day), n=23,22
|
2010 mL/h
Geometric Coefficient of Variation 37.7
|
1780 mL/h
Geometric Coefficient of Variation 44.3
|
—
|
—
|
|
CL/F,ss
300 mg XR QD (250-349 mg IR/day), n=11,12
|
2080 mL/h
Geometric Coefficient of Variation 50.1
|
2240 mL/h
Geometric Coefficient of Variation 32.9
|
—
|
—
|
|
CL/F,ss
400 mg XR QD (≥350 mg IR/day), n=11,15
|
3700 mL/h
Geometric Coefficient of Variation 60.7
|
2640 mL/h
Geometric Coefficient of Variation 39.3
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 11 prior to the next scheduled dose of Nevirapine IR and day 22 prior to the next scheduled dose of Nevirapine XRPopulation: Intensive PK analysis set (IPK): This patient set includes all patients in the PK set that underwent intensive PK sampling.
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.
Outcome measures
| Measure |
NVP XR
n=45 Participants
Nevirapine XR (extended release)
|
NVP IR
n=49 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
Cavg
400 mg XR QD (≥350 mg IR/day), n=11,15
|
4510 ng/mL
Geometric Coefficient of Variation 60.7
|
6120 ng/mL
Geometric Coefficient of Variation 39.8
|
—
|
—
|
|
Cavg
200 mg XR QD (175-249 mg IR/day), n=23,22
|
4140 ng/mL
Geometric Coefficient of Variation 37.7
|
4820 ng/mL
Geometric Coefficient of Variation 45.7
|
—
|
—
|
|
Cavg
300 mg XR QD (250-349 mg IR/day), n=11,12
|
6010 ng/mL
Geometric Coefficient of Variation 50.1
|
4840 ng/mL
Geometric Coefficient of Variation 35.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 22Population: Full analysis set including patients with available viral load data at day 22
Patients maintaining a viral load \< 50 copies/mL at Day 22.
Outcome measures
| Measure |
NVP XR
n=25 Participants
Nevirapine XR (extended release)
|
NVP IR
n=23 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
n=31 Participants
Patients 12 to \< 18 years old.
|
Total.
n=79 Participants
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).
|
|---|---|---|---|---|
|
Efficacy: Patients Maintaining a VL < 50 Copies/mL
|
96.0 percentage of patients
|
100.0 percentage of patients
|
100.0 percentage of patients
|
98.7 percentage of patients
|
SECONDARY outcome
Timeframe: Day 22Population: Full analysis set including patients with available viral load data at day 22
Patients maintaining a viral load \< 400 copies/mL at Day 22
Outcome measures
| Measure |
NVP XR
n=25 Participants
Nevirapine XR (extended release)
|
NVP IR
n=23 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
n=31 Participants
Patients 12 to \< 18 years old.
|
Total.
n=79 Participants
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).
|
|---|---|---|---|---|
|
Efficacy: Patients Maintaining a VL < 400 Copies/mL
|
100.0 percentage of patients
|
100.0 percentage of patients
|
100.0 percentage of patients
|
100.0 percentage of patients
|
SECONDARY outcome
Timeframe: Baseline, Day 22 and week 24Population: 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.
Change in mean CD4+ count (absolute) from baseline to Day 22 and from baseline to Week 24.
Outcome measures
| Measure |
NVP XR
n=24 Participants
Nevirapine XR (extended release)
|
NVP IR
n=24 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
n=31 Participants
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
Change From Baseline in Mean CD4+ Count (Absolute)
Day 22
|
-115.6 cells/mm^3
Standard Deviation 320.5
|
24.2 cells/mm^3
Standard Deviation 184.8
|
60.3 cells/mm^3
Standard Deviation 171.2
|
—
|
|
Change From Baseline in Mean CD4+ Count (Absolute)
Week 24 (n=8;10;9)
|
-214.5 cells/mm^3
Standard Deviation 397.5
|
-51.2 cells/mm^3
Standard Deviation 179.4
|
31.1 cells/mm^3
Standard Deviation 66.4
|
—
|
SECONDARY outcome
Timeframe: Baseline to day 22 and baseline to week 24Population: 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.
((Day 22 value-Baseline value)/Baseline value)\*100. ((Week 24 value-Baseline value)/Baseline value)\*100.
Outcome measures
| Measure |
NVP XR
n=24 Participants
Nevirapine XR (extended release)
|
NVP IR
n=24 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
n=31 Participants
Patients 12 to \< 18 years old.
|
Total.
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).
|
|---|---|---|---|---|
|
Percentage Change From Baseline in Mean CD4+ Count
Week 24 (n=8, 10, 9)
|
-2.1 percentage change
Standard Deviation 4.0
|
-2.1 percentage change
Standard Deviation 3.4
|
-1.0 percentage change
Standard Deviation 2.9
|
—
|
|
Percentage Change From Baseline in Mean CD4+ Count
Day 22
|
-2.1 percentage change
Standard Deviation 6.7
|
-0.0 percentage change
Standard Deviation 2.5
|
0.5 percentage change
Standard Deviation 3.6
|
—
|
SECONDARY outcome
Timeframe: week 24Population: Full analysis set including patients with available viral load data at week 24
Patients maintaining a viral load \< 50 copies/mL at week 24 (approximately 168 days) of Optional Extension Phase (OEP).
Outcome measures
| Measure |
NVP XR
n=8 Participants
Nevirapine XR (extended release)
|
NVP IR
n=10 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
n=9 Participants
Patients 12 to \< 18 years old.
|
Total.
n=27 Participants
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).
|
|---|---|---|---|---|
|
Efficacy: Patients Maintaining a VL < 50 Copies/mL at Week 24 of Optional Extension Phase
|
100.0 percentage of patients
|
100.0 percentage of patients
|
100.0 percentage of patients
|
100.0 percentage of patients
|
SECONDARY outcome
Timeframe: week 24Population: Full analysis set including patients with available viral load data at week 24
Patients maintaining a viral load \< 400 copies/mL at week 24 of the Optional Extension Phase (OEP)
Outcome measures
| Measure |
NVP XR
n=8 Participants
Nevirapine XR (extended release)
|
NVP IR
n=10 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
n=9 Participants
Patients 12 to \< 18 years old.
|
Total.
n=27 Participants
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).
|
|---|---|---|---|---|
|
Efficacy: Patients Maintaining a VL < 400 Copies/mL in Optional Extension Phase
|
100.0 percentage of patients
|
100.0 percentage of patients
|
100.0 percentage of patients
|
100.0 percentage of patients
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Last available visit, up to 155 weeksPopulation: Optional Extension Phase Treated Set (OEP TS), all patients that complete PK phase and enroll in Extension phase with VL data available
Patients maintaining a viral load \< 50 copies/mL at the last available visit
Outcome measures
| Measure |
NVP XR
n=12 Participants
Nevirapine XR (extended release)
|
NVP IR
n=16 Participants
Nevirapine IR (immediate release)
|
12-<18 yr
n=12 Participants
Patients 12 to \< 18 years old.
|
Total.
n=40 Participants
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).
|
|---|---|---|---|---|
|
Efficacy: Patients Maintaining a VL < 50 Copies/mL at Last Available Visit
|
100.0 percentage of patients
|
100.0 percentage of patients
|
100.0 percentage of patients
|
100.0 percentage of patients
|
Adverse Events
Total.
Serious adverse events
| Measure |
Total.
n=85 participants at risk
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).
|
|---|---|
|
Infections and infestations
Coxsackie viral infection
|
1.2%
1/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Infections and infestations
Pneumonia
|
1.2%
1/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Injury, poisoning and procedural complications
Concussion
|
1.2%
1/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
1.2%
1/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
1.2%
1/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Surgical and medical procedures
Tonsillectomy
|
1.2%
1/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
Other adverse events
| Measure |
Total.
n=85 participants at risk
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).
|
|---|---|
|
Eye disorders
Conjunctivitis
|
12.9%
11/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
5.9%
5/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Gastrointestinal disorders
Vomiting
|
8.2%
7/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
General disorders
Pyrexia
|
9.4%
8/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Infections and infestations
Body tinea
|
5.9%
5/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Infections and infestations
Bronchitis
|
5.9%
5/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Infections and infestations
Nasopharyngitis
|
5.9%
5/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Infections and infestations
Respiratory tract infection
|
7.1%
6/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Infections and infestations
Rhinitis
|
9.4%
8/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Infections and infestations
Tinea capitis
|
8.2%
7/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Infections and infestations
Upper respiratory tract infection
|
38.8%
33/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Infections and infestations
Viral upper respiratory tract infection
|
10.6%
9/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Nervous system disorders
Headache
|
16.5%
14/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
32.9%
28/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
23.5%
20/85 • From the first drug administration until 14 days after the last drug administration, up to 157 weeks
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER