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

Teva Pharmaceuticals

Status and phase

Completed

Phase 1

Conditions

Traumatic Brain Injury

Treatments

Drug: Sublingual Tizanidine HCl

Study type

Interventional

Funder types

Industry

Identifiers

NCT00287157

Protocol C2/5/TZ-TBI-01

Details and patient eligibility

About

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).

Full 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.

Enrollment

5 patients

Sex

All

Ages

8 to 18 years old

Volunteers

No Healthy Volunteers

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