One Year Extension Study To Protocol C2/5/TZ:MS-05

Teva Pharmaceuticals

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Spasticity

Multiple Sclerosis

Treatments

Drug: sublingual tizanidine 12 mg

Study type

Interventional

Funder types

Industry

Identifiers

NCT00464958

Protocol C2/5/TZ:MS-05 EXT

Details and patient eligibility

About

Open label, one year extension study to evaluate the clinical efficacy and safety of 12 mg sublingual tizanidine administered once nightly in MS patients who successfully completed Phase I/II protocol C2/5/TZ:MS-05 at the Tel Aviv Sourasky Medical Center, Department of Neurology, Dr. Arnon Karni, PI.

Full description

The previous study, Protocol C2/5/TZ-MS-05, using 12 mg sublingual tizanidine, confirmed that administration of once nightly sublingual tizanidine before sleep results in a statistically and clinically significant reduction in next-day spasticity, as compared to placebo. The clinical effect following 12 mg sublingual tizanidine was larger (4-5 units on the Ashworth scale) and more sustained (up to 18-20 hours post-dose) than was seen for 8 mg tizanidine (earlier study, Protocol C2/5/TZ:MS-03z). This study also reconfirmed that the increased improvement in next-day reduction of spasticity following overnight sublingual tizanidine dosing is not accompanied by a concomitant increase in next-day somnolence.

This study, a 12 month open label extension, will allow those patients who successfully completed Protocol C2/5/TZ-MS-05 and who found tizanidine to be beneficial, to continue treatment under close medical supervision. The study will provide long-term (12 months) clinical efficacy and safety data re: the use of once daily sublingual tizanidine, administered at night, just before bedtime.

Enrollment

10 patients

Sex

All

Ages

20 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Successful completion of previous protocol, Study C2/5/TZ:MS-05
Have a definitive diagnosis of Multiple Sclerosis
Patients may be allowed to take other anti-spasticity medication during the study (other than Baclofen pump)as per their individual daily dosing regimen, with the following qualification: (1) No dose after 18:00 on any study day (2) No dose at all on a clinic evaluation day
Females must agree to use a medically accepted form of birth control, be surgically sterile, or be two years post-menopausal. Oral contraception in NOT acceptable as it is contraindicated for tizanidine use.
Patients must meet criteria for stable 24 hour BP values based on the screening ABPM monitorings (with and without tizanidine challenge) as determined by the study's BP consultant

Exclusion criteria

Use of CYP1A2 inhibitors [e.g. ciprofloxacin or fluvoxamine as well as zileuton, other fluroquinolones (norfloxacin), antiarrythmics (amiodarone, mexiletine, propafenone), cimetidine, famotidine, oral contraceptives, acyclovir, and ticlopidine] from baseline and for the duration of the study
Taking medications from baseline and for the duration of the study that would potentially interfere with the actions of the study medication or outcome variables as determined by the PI
Previous history of dementia, unstable psychiatric disease or current signs and symptoms of significant medical disorders such as severe, progressive or uncontrolled renal, hepatic hematological, endocrine, pulmonary, cardiac, neurological or cerebral disease
Significant abnormalities in screening laboratory parameters as described below:
ALT > 2xULN
AST > 2xULN
Creatinine > 2.0 mg/dL
Bilirubin > 2xULN
WBC < 2,300/mm3
Platelets < 80,000/mm3
History of allergy to tizanidine or any inactive component (including lactose intolerance) of the sublingual tizanidine tablet
History of substance abuse within past 12 months
Patients who are non-cooperative or unwilling to sign consent form