Safety and Preliminary Effectiveness of AV650 in Patients With Spasticity Associated With Multiple Sclerosis

Study Overview
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Brief Summary
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A drug called AV650 (tolperisone HCl) will be given to patients who have spasticity associated with multiple sclerosis. This study has three purposes: To determine whether AV650 is safe for patients with multiple sclerosis; To gather some early evidence as to whether AV650 is effective in treating spasticity in patients with multiple sclerosis; and, To assess what the body does with AV650 once it is ingested (Germany and Czech Republic sites only).

Official Title
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AV650-018: A Two-Part (Double-Blind Followed by Open-Label), Placebo Controlled, Randomized Trial to Assess the Safety, Tolerability, and Preliminary Efficacy of AV650 (Tolperisone HCl) in Subjects With Spasticity Associated With Multiple Sclerosis

Conditions
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Muscle Spasticity

Intervention / Treatment
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* Drug: tolperisone HCl
* Drug: tolperisone HCl
* Drug: tolperisone HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects between 18 and 70 years of age (inclusive) Signed and dated informed consent Definite MS as per Poser or MacDonald Criteria (either relapsing remitting or secondary progressive course) Expanded Disability Status Score (EDSS) from 3.0 to 6.5 (inclusive) at Screening Stable MS for at least 30 days before screening Female of child bearing potential and male subjects whose partner is of child bearing potential who are willing to ensure that they or their partner use effective double-barrier contraception during the study and for 90 days thereafter If female, be neither pregnant nor nursing (Confirmation that the subject is not pregnant must be established by a negative serum hCG pregnancy test at baseline.) Significant spasticity in at least two muscle groups defined as a score of 2 or more on the Ashworth scale for each muscle group If a subject is on anti-spastic treatments, the dosage, frequency, and route of administration must be stable for at least 30 days before Screening If a subject is on MS treatments, the dosage, frequency, and route of administration must be stable for at least 30 days before Screening Exclusion Criteria: Subjects who have participated in another research study within 90 days of Screening Significant changes in anti-spasticity medications (dosage, frequency, or route of administration) within 30 days of Screening Known hypersensitivity to tolperisone HCl, its components, or other lidocaine/lidocaine-like products Use of tolperisone HCl within 30 days of screening Significant changes in MS treatments (dosage, frequency, or route of administration) within 30 days of Screening Spasticity due to neurological disorders other than MS Any psychiatric disorder or cognitive impairment that precludes fully informed consent or safe participation in the study Subjects who have suffered an acute relapse of MS or who continue to suffer from an acute relapse of MS within 90 days of Baseline History of alcohol or substance abuse within one year of Screening Concurrent clinically significant immunologic, pulmonary, renal, hepatic, or endocrine disease and/or other unstable or major disease other than MS Clinically significant cardiovascular disorders, such as ischemic heart disease, arrhythmias, poorly controlled hypertension, or acute myocardial infarction QT prolongation greater than 480 msec or greater than 450 msec if accompanied by a partial bundle branch block, or other ECG abnormality in the judgment of the Investigator Diastolic blood pressure <50mmHg or >105mmHg; heart rate <50 beats per minute (bpm) or >110bpm, after 3 minutes in a sitting position; heart rate by ECG <50bpm or >110bpm History of epilepsy (except childhood febrile seizures) Current malignancy or history of malignancy that has not been in remission for more than five years, except basal cell skin carcinoma and cervical cancer (with treatment) Female subject who is pregnant, nursing, or planning pregnancy during the course of the study Scheduled elective surgery or other procedures requiring general anesthesia during the study Subject who is terminally ill in the judgment of the Investigator Subject who is inappropriate for placebo medication in the judgment of the Investigator Systemic corticosteroid therapy within 28 days of randomization, with the exception of inhaled medications for asthma Exacerbation of MS within 30 days of Baseline Regular levo-dopa therapy within 7 days of randomization Subjects taking antiarrhythmic medications Donation of blood during the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AV650 low dose | Drug: tolperisone HCl<br>* Low dose AV650 three times a day orally for 5 weeks; followed by optional continuation on either low dose or high dose AV650, as tolerated, for 24 weeks<br>|
| Experimental: 2<br>AV650 high dose | Drug: tolperisone HCl<br>* High dose AV650 three times a day orally for 5 weeks; followed by optional continuation on either low dose or high dose AV650, as tolerated, for 24 weeks<br>|
| Experimental: 3<br>Placebo | Drug: tolperisone HCl<br>* Placebo three times a day orally for 5 weeks; followed by optional continuation on either low dose or high dose AV650, as tolerated, for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the long-term safety and tolerability of AV650 (tolperisone HCl) in subjects with spasticity associated with MS |  | 38 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine preliminary efficacy of AV650 as compared to placebo in subjects with spasticity associated with MS; and to determine the pharmacokinetic (PK) profile of AV650 at two dose levels |  | 38 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis