Spasticity Due to Cerebral Palsy
Conditions
Brief summary
A Single-Dose, Phase 1b, Multicenter, Open-Label Study to Assess the Pharmacokinetics, Safety and Tolerability, and Pharmacodynamics of Tizanidine at 4 Different Oral Dose Levels in Pediatric Subjects 2 to 16 Years Old With Mild to Moderate Spasticity Due to Cerebral Palsy.
Detailed description
Evaluation of the study's progress after the amendment remained challenging with continued pre-screen failures noted in areas of Botox injection inclusion; family participation refusal / disinterest and gastric or jejunostomy tube placement. A third protocol amendment to improve enrollment was discussed with the Investigators who did not believe further amendment would overcome the barriers expressed by parents that would subject their children to an intense study time commitment without direct benefit. The investigative sites were notified that the study was closed to enrollment March 27, 2012.
Interventions
DRUGZanaflex Capsules
0.025 mg/kg
Sponsors
Syneos Health
Acorda Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Have clinically diagnosed spasticity resulting from cerebral palsy * Have a motor disability resulting from a static, nonprogressive brain injury or malformation occurring prenatally or before the age of 2 years * Have mild to moderate spasticity at screening * Have a parent or legally accepted representative able to understand and comply with study requirements who voluntarily provides informed consent and agrees to be primarily responsible for adhering to the requirements of the study
Exclusion criteria
* Have a history of hypersensitivity or allergic reaction to tizanidine or any of the capsule components * Have dietary restrictions or food allergies that conflict with a standardized meal * Have clinically significant psychiatric, gastrointestinal, pulmonary, hematologic, endocrine, cardiovascular, renal, or hepatic disease that requires pharmacologic intervention * Have an ongoing seizure disorder that requires medical therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter AUC0-8 (Area Under the Concentration-time Curve From Time 0 to 8 Hours) of a Single Dose of Tizanidine at 4 Different Dose Levels in Children and Adolescents With Cerebral Palsy and Mild to Moderate Spasticity. | Baseline and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours | Baseline: immediately before the standardized meal (i.e., before administration of tizanidine) on dosing day 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after administration of tizanidine PK parameters will be derived by using WinNonlin Pro (version 5.0.1 or later, Pharsight Corp). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic (PK) Parameter Cmax (Maximum Observed Drug Concentration in Plasma) of a Single Dose of Tizanidine at 4 Different Dose Levels in Children and Adolescents With Cerebral Palsy and Mild to Moderate Spasticity. | Baseline and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours | Baseline: immediately before the standardized meal (i.e., before administration of tizanidine) on dosing day 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after administration of tizanidine PK parameters will be derived by using WinNonlin Pro (version 5.0.1 or later, Pharsight Corp). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1 Zanaflex Capsules : 0.025 mg/kg | 8 |
| Dose Level 2 Zanaflex Capsules : 0.05 mg/kg | 2 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Dose Level 2 | Dose Level 1 |
|---|---|---|---|
| Age, Customized 13-16 years | 1 participants | 0 participants | 1 participants |
| Age, Customized 2-3 years | 3 participants | 0 participants | 3 participants |
| Age, Customized 4-5 years | 1 participants | 0 participants | 1 participants |
| Age, Customized 6-12 years | 5 participants | 2 participants | 3 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 2 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 1 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 8 | 2 / 2 |
| serious Total, serious adverse events | 0 / 8 | 0 / 2 |
Outcome results
Primary
Pharmacokinetic (PK) Parameter AUC0-8 (Area Under the Concentration-time Curve From Time 0 to 8 Hours) of a Single Dose of Tizanidine at 4 Different Dose Levels in Children and Adolescents With Cerebral Palsy and Mild to Moderate Spasticity.
Baseline: immediately before the standardized meal (i.e., before administration of tizanidine) on dosing day 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after administration of tizanidine PK parameters will be derived by using WinNonlin Pro (version 5.0.1 or later, Pharsight Corp).
Time frame: Baseline and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours
Population: Pharmacokinetics Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Level 1 | Pharmacokinetic (PK) Parameter AUC0-8 (Area Under the Concentration-time Curve From Time 0 to 8 Hours) of a Single Dose of Tizanidine at 4 Different Dose Levels in Children and Adolescents With Cerebral Palsy and Mild to Moderate Spasticity. | 5.60 hour*nanogram/mililiter | Standard Error 1.79 |
| Dose Level 2 | Pharmacokinetic (PK) Parameter AUC0-8 (Area Under the Concentration-time Curve From Time 0 to 8 Hours) of a Single Dose of Tizanidine at 4 Different Dose Levels in Children and Adolescents With Cerebral Palsy and Mild to Moderate Spasticity. | 6.11 hour*nanogram/mililiter | Standard Error 1.29 |
Secondary
Pharmacokinetic (PK) Parameter Cmax (Maximum Observed Drug Concentration in Plasma) of a Single Dose of Tizanidine at 4 Different Dose Levels in Children and Adolescents With Cerebral Palsy and Mild to Moderate Spasticity.
Baseline: immediately before the standardized meal (i.e., before administration of tizanidine) on dosing day 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after administration of tizanidine PK parameters will be derived by using WinNonlin Pro (version 5.0.1 or later, Pharsight Corp).
Time frame: Baseline and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours
Population: Pharmacokinetics Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Dose Level 1 | Pharmacokinetic (PK) Parameter Cmax (Maximum Observed Drug Concentration in Plasma) of a Single Dose of Tizanidine at 4 Different Dose Levels in Children and Adolescents With Cerebral Palsy and Mild to Moderate Spasticity. | 1.87 nanogram/mililiter | Standard Error 0.6 |
| Dose Level 2 | Pharmacokinetic (PK) Parameter Cmax (Maximum Observed Drug Concentration in Plasma) of a Single Dose of Tizanidine at 4 Different Dose Levels in Children and Adolescents With Cerebral Palsy and Mild to Moderate Spasticity. | 5.29 nanogram/mililiter | Standard Error 0.05 |