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

• Sponsor: Acorda Therapeutics (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01405950
• Collaborator: Syneos Health (Other)
• Enrollment: 10
• Location: 1
• Arms: 4
• Duration (Months): 10
• Patients Per Site Per Month: 1

Study Details

Study Description

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; Drug: Zanaflex Capsules; Drug: Zanaflex Capsules; 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

• Study Type: Interventional
• 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 1, 2011
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

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

Outcome Measures

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. [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. [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

Criteria

• Ages Eligible for Study: 2 Years to 16 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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
• Syneos Health

Investigators

• Study Director: Herbert Henney, PharmD, Acorda Therapeutics

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acorda Therapeutics
• ClinicalTrials.gov Identifier: NCT01405950
• Other Study ID Numbers: AT10-ZC-08
• First Posted: Jul 29, 2011
• Last Update Posted: Jun 17, 2013
• Last Verified: Jun 1, 2013

• Additional relevant MeSH terms: Muscle Spasticity; Cerebral Palsy; Clonidine; Tizanidine

Study Results

Participant Flow

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4
Arm/Group Description	Zanaflex Capsules : 0.025 mg/kg	Zanaflex Capsules : 0.05 mg/kg	Zanaflex Capsules : 0.075 mg/kg	Zanaflex Capsules : 0.1 mg/kg
Period Title: Overall Study
STARTED	8	2	0	0
COMPLETED	7	2	0	0
NOT COMPLETED	1	0	0	0

Baseline Characteristics

Arm/Group Title	Dose Level 1	Dose Level 2	Total
Arm/Group Description	Zanaflex Capsules : 0.025 mg/kg	Zanaflex Capsules : 0.05 mg/kg	Total of all reporting groups
Overall Participants	8	2	10
Age, Customized (participants) [Number]
2-3 years	3 37.5%	0 0%	3 30%
4-5 years	1 12.5%	0 0%	1 10%
6-12 years	3 37.5%	2 100%	5 50%
13-16 years	1 12.5%	0 0%	1 10%
Sex: Female, Male (Count of Participants)
Female	5 62.5%	1 50%	6 60%
Male	3 37.5%	1 50%	4 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	8 100%	2 100%	10 100%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetics Population

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4
Arm/Group Description	Zanaflex Capsules : 0.025 mg/kg	Zanaflex Capsules : 0.05 mg/kg	Zanaflex Capsules: 0.075 mg/kg	Zanaflex Capsules: 0.1 mg/kg
Measure Participants	7	2	0	0
Mean (Standard Error) [hour*nanogram/mililiter]	5.60 (1.79)	6.11 (1.29)

2. Secondary Outcome

Title	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.
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetics Population

Arm/Group Title	Dose Level 1	Dose Level 2	Dose Level 3	Dose Level 4
Arm/Group Description	Zanaflex Capsules : 0.025 mg/kg	Zanaflex Capsules : 0.05 mg/kg	Zanaflex Capsules: 0.075 mg/kg	Zanaflex Capsules: 0.1 mg/kg
Measure Participants	7	2	0	0
Mean (Standard Error) [nanogram/mililiter]	1.87 (0.60)	5.29 (0.05)

Adverse Events

Time Frame	Up to 30 days.
Adverse Event Reporting Description	Treatment-emergent adverse events (TEAE) were defined as AEs with date/time of onset (or worsening) on or after the start-date/time of administration of study drug and no more than 1 day after the last dose of study drug.
Arm/Group Title	Dose Level 1		Dose Level 2
Arm/Group Description	Zanaflex Capsules : 0.025 mg/kg		Zanaflex Capsules : 0.05 mg/kg
All Cause Mortality
	Dose Level 1		Dose Level 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Dose Level 1		Dose Level 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Dose Level 1		Dose Level 2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)		2/2 (100%)
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness	0/8 (0%)	0	1/2 (50%)	1
Nervous system disorders
Somnolence	1/8 (12.5%)	1	2/2 (100%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor (Acorda) has right to review and comment on proposed publications within a specified time frame, up to 60 days; multi-center trials require joint publication unless specifically permitted otherwise.