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

Primary Purpose

Spasticity, Multiple Sclerosis

Status

Terminated

Phase

Phase 1

Locations

Israel

Study Type

Interventional

Intervention

sublingual tizanidine 12 mg

About this trial

This is an interventional treatment trial for Spasticity focused on measuring Fatigue, Spasticity, Sublingual Tizanidine, Epworth Sleepiness Scale, Fatigue Severity Scale

Eligibility Criteria

20 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

Tel Aviv Sourasky Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sublingual tizanidine

Arm Description

Once nightly dosing of 12 mg sublingual tizanidine tablet

Outcomes

Primary Outcome Measures

Clinical Efficacy- reduction in next-day spasticity (Ashworth scores)

Safety- No increase in next-day somnolence/fatigue, measured via Epworth Sleepiness Scale (ESS) and Fatigue Severity Scale (FSS) questionnaires

Secondary Outcome Measures

Additional Safety Measures: Clinical Laboratories (hematology and clinical chemistry, with special emphasis on liver function tests); Blood pressure monitoring (standard vital signs: BP and pulse at every monthly visit, + 24 hour Holter ambulatory Blood

Full Information

NCT ID

NCT00464958

First Posted

April 22, 2007

Last Updated

February 17, 2009

Sponsor

Teva GTC

1. Study Identification

Unique Protocol Identification Number

NCT00464958

Brief Title

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

Official Title

Long Term Clinical Efficacy and Safety of Novel Sublingual Tizanidine HCl (12 mg) for the Treatment of Spasticity in Patients With Multiple Sclerosis - Open Label Extension Study

Study Type

Interventional

2. Study Status

Record Verification Date

January 2009

Overall Recruitment Status

Terminated

Why Stopped

Study was stopped as the sponsor is no longer funding this project

Study Start Date

January 2008 (undefined)

Primary Completion Date

December 2008 (Actual)

Study Completion Date

December 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Teva GTC

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Spasticity, Multiple Sclerosis

Keywords

Fatigue, Spasticity, Sublingual Tizanidine, Epworth Sleepiness Scale, Fatigue Severity Scale

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sublingual tizanidine

Arm Type

Experimental

Arm Description

Once nightly dosing of 12 mg sublingual tizanidine tablet

Intervention Type

Drug

Intervention Name(s)

sublingual tizanidine 12 mg

Intervention Description

Single sublingual tizanidine 12 mg tablet, to be administered once nightly, via sublingual administration for 12 months

Primary Outcome Measure Information:

Title

Clinical Efficacy- reduction in next-day spasticity (Ashworth scores)

Time Frame

12 months

Title

Safety- No increase in next-day somnolence/fatigue, measured via Epworth Sleepiness Scale (ESS) and Fatigue Severity Scale (FSS) questionnaires

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Arnon Karni, MD

Organizational Affiliation

Tel-Aviv Sourasky Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Tel Aviv Sourasky Medical Center

City

Tel Aviv

ZIP/Postal Code

64239

Country

Israel

12. IPD Sharing Statement

Links:

URL

http://www.clinicaltrials.gov/ct2/results?term=NCT00358293

Description

ClinicalTrials.gov Identifier: NCT00358293

Learn more about this trial

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

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