Phase 1b Study of Tizanidine in Pediatric Patients With Cerebral Palsy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Single-Dose, Phase 1b Study to Assess Pharmacokinetics, Safety and Tolerability, and Pharmacodynamics of Tizanidine at 4 Different Oral Dose Levels in Pediatric Subjects With Mild to Moderate Spasticity Due to Cerebral Palsy

Conditions
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Spasticity Due to Cerebral Palsy

Intervention / Treatment
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* Drug: Zanaflex Capsules
* Drug: Zanaflex Capsules
* Drug: Zanaflex Capsules
* Drug: Zanaflex Capsules


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1<br> | Drug: Zanaflex Capsules<br>* 0.025 mg/kg<br>* Other names: tizanidine HCI (hydrochloride);|
| Experimental: Dose Level 2<br> | Drug: Zanaflex Capsules<br>* 0.05 mg/kg<br>* Other names: tizanidine HCI (hydrochloride);|
| Experimental: Dose Level 3<br> | Drug: Zanaflex Capsules<br>* 0.075 mg/kg<br>* Other names: tizanidine HCI (hydrochloride);|
| Experimental: Dose Level 4<br> | Drug: Zanaflex Capsules<br>* 0.1 mg/kg<br>* Other names: tizanidine HCI (hydrochloride);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | Baseline and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours |