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

• Safety and Tolerability [ Time Frame: Up to 30 days: screening, treatment, follow-up ] [ Designated as safety issue: No ]

  Screening period: less then or equal to 28 days

  Treatment period: 1 day (single dose of tizanidine)

  Follow-up period: 1 day (telephone contact the day after administration of tizanidine)

  Assessments performed both before and after administration of tizanidine include vital sign measurements, physical examination, clinical laboratory tests of blood and urine, and electrocardiograms (ECGs).

• Pharmacodynamics [ Time Frame: screening, baseline, after dosing ] [ Designated as safety issue: No ]

  Pharmacodynamic measurement will be performed by using the Modified Ashworth Scale

  screening; completed for all applicable major muscle groups

  baseline; before the standardized meal (before administration of tizanidine)on the dosing day

  after dosing; 1,2,3,4,6 and 8 hours after administration of tizanidine

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.

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.

• Drug: Zanaflex Capsules
  0.025 mg/kg
  Other Name: tizanidine HCI (hydrochloride)
• Drug: Zanaflex Capsules
  0.05 mg/kg
  Other Name: tizanidine HCI (hydrochloride)
• Drug: Zanaflex Capsules
  0.075 mg/kg
  Other Name: tizanidine HCI (hydrochloride)
• Drug: Zanaflex Capsules
  0.1 mg/kg
  Other Name: tizanidine HCI (hydrochloride)

• Experimental: Dose Level 1
  Intervention: Drug: Zanaflex Capsules
• Experimental: Dose Level 2
  Intervention: Drug: Zanaflex Capsules
• Experimental: Dose Level 3
  Intervention: Drug: Zanaflex Capsules
• Experimental: Dose Level 4
  Intervention: Drug: Zanaflex Capsules

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