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

This study has been terminated.
(Please see 'Further study details as provided by Acorda Therapeutics' for explanation of why study stopped.)
Sponsor:
Collaborator:
INC Research
Information provided by (Responsible Party):
Acorda Therapeutics
ClinicalTrials.gov Identifier:
NCT01405950
First received: July 25, 2011
Last updated: June 10, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Spasticity Due to Cerebral Palsy
Drug: Zanaflex Capsules
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Acorda Therapeutics:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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:
  • 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 ] [ Designated as safety issue: No ]

    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).



Enrollment: 10
Study Start Date: May 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

Ages Eligible for Study:   2 Years to 16 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01405950

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

No publications provided

Responsible Party: Acorda Therapeutics
ClinicalTrials.gov Identifier: NCT01405950     History of Changes
Other Study ID Numbers: AT10-ZC-08
Study First Received: July 25, 2011
Results First Received: March 27, 2013
Last Updated: June 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Muscle Spasticity
Cerebral Palsy
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Brain Damage, Chronic
Brain Diseases
Central Nervous System Diseases
Tizanidine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Muscle Relaxants, Central
Neuromuscular Agents
Parasympatholytics
Autonomic Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on September 30, 2014