Pilot, Proof-of-Concept Study of Sublingual Tizanidine in Children With Chronic Traumatic Brain Injury (TBI)

Condition(s) targeted: Traumatic Brain Injury

Intervention: Sublingual Tizanidine HCl (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Teva R&D Initiative

Official(s) and/or principal investigator(s):
Ido Yatsiv, MD, Principal Investigator, Affiliation: Hadassah Medical Center, Ein Kerem, Jerusalem

Nightly administration of a unique, sublingual (under the tongue) formulation of tizanidine, a known anti-spasticity medication, has been shown in a previous study to improve sleep and next-day functioning in CP (cerebral palsy) patients. It is hypothesized that this improvement in sleep efficiency (i. e.,fewer wake episodes, longer time asleep, etc.) with resulting improvement in quality-of-life (i. e.,improvements in next-day functioning, cognition and movement) may also be seen in a similar patient population, i. e., children with traumatic brain injury (TBI).

Official title: A Double-Blind, Randomized, Two-Way Crossover, Comparative Study to Evaluate the Clinical Efficacy and Safety of Novel Sublingual Tizanidine HCl Versus Placebo in Children With Chronic Traumatic Brain Injury

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study

Primary outcome: Improvement in Spasticity, Cognition and Daily Function

Secondary outcome: Improvement in nighttime actigraphy sleep parameters

Detailed description: Sublingual tizanidine, a novel test formulation of the known effective antispasticity agent, has been shown to have a unique pharmacokinetic profile [(i. e., nearly twice the bioavailability/AUC), but with little or no increase in peak plasma levels (Cmax), as compared to oral tizanidine (Zanaflex)]. When administered nightly to CP (Cerebral Palsy) patients to more effectively reduce the muscle spasms that disrupt sleep, it was shown to improve sleep efficiency, decrease sleep fragmentation and improve the sleep cycle. This improvement in night-time sleep was translated into a potential improvement in next-day functioning (improvement in next-day measures of spasticity and movement).

It is hypothesized that a similar type of improvement in sleep with consequent positive impact on next day improvement in spasticity, cognition and function, may also be manifest in a similar patient population, children with traumatic brain injury.

Minimum age: 8 Years. Maximum age: 18 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Males/Females 8-18 years of age with documented history of TBI

- Documented Loss of Consciousness(LOC) for more than 24 H, or initial GCS (Glasgow Coma

Score) lower than 8

- Current Spasticity that interferes with task performance

- Patient is able to cooperate and understand general explanations

Exclusion Criteria:

- History of allergy to tizanidine or any inactive component (including lactose

intolerance)

- Use of other hypnotic medication within 3 days of baseline visit and during the study

- Botox therapy within 6 weeks of baseline, or use of Baclofen pump during the trial

- Use of CYP1A2 inhibitors (ex. ciprofloxacin or fluvoxamine) for the duration of the

study

- Female patients on oral contraceptives

- Significant abnormalities in clinical screening laboratory parameters (ALT, AST,

Bilirubin>2 x uln; Creatinine>2 mg/dl;WBC <2300/mm3, platelets<80,000/mm3)

- Taking of other medications that may adversely interfere with the actions of the study

medication or outcome variables within 2 weeks of 5 half-lives of the baseline visit

Alyn Hospital Pediatric and Adolescent Rehabilitation Center, Jerusalem 01090, Israel

Starting date: December 2006
Ending date: May 2007
Last updated: September 10, 2007