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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Spasticity Due to Cerebral Palsy	Drug: Zanaflex Capsules	Phase 1

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
Allocation:	Non-Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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
Study Start Date :	May 2011
Actual Primary Completion Date :	March 2012
Actual Study Completion Date :	March 2012

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: Dose Level 1	Drug: Zanaflex Capsules; 0.025 mg/kg; Other Name: tizanidine HCI (hydrochloride)
Experimental: Dose Level 2	Drug: Zanaflex Capsules; 0.05 mg/kg; Other Name: tizanidine HCI (hydrochloride)
Experimental: Dose Level 3	Drug: Zanaflex Capsules; 0.075 mg/kg; Other Name: tizanidine HCI (hydrochloride)
Experimental: Dose Level 4	Drug: Zanaflex Capsules; 0.1 mg/kg; Other Name: tizanidine HCI (hydrochloride)

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

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. [ Time Frame: 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 Outcome Measures :

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. [ Time Frame: 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).

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	2 Years to 16 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Kentucky
University of Louisville Department of Neurology dba Kentucky Neuroscience Research Health Care Outpatient Center (HCOC)
Louisville, Kentucky, United States, 40202

Sponsors and Collaborators

Acorda Therapeutics

INC Research

Investigators

Study Director:	Herbert Henney, PharmD	Acorda Therapeutics

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Acorda Therapeutics
ClinicalTrials.gov Identifier:	NCT01405950 History of Changes
Other Study ID Numbers:	AT10-ZC-08
First Posted:	July 29, 2011
Results First Posted:	May 13, 2013
Last Update Posted:	June 17, 2013
Last Verified:	June 2013

Additional relevant MeSH terms:

Paralysis; Cerebral Palsy; Brain Damage, Chronic; Brain Diseases; Muscle Spasticity; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Central Nervous System Diseases; Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Tizanidine; Clonidine	Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Muscle Relaxants, Central; Neuromuscular Agents; Parasympatholytics; Autonomic Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action