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

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

A drug called AV650 (tolperisone HCl) will be given to patients who have spasticity associated with multiple sclerosis. This study has three purposes:

1. To determine whether AV650 is safe for patients with multiple sclerosis;
2. To gather some early evidence as to whether AV650 is effective in treating spasticity in patients with multiple sclerosis; and,
3. To assess what the body does with AV650 once it is ingested (Germany and Czech Republic sites only).

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