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).

Study Overview

• Status: Terminated
• Conditions: Muscle Spasticity
• Intervention / Treatment: Drug: tolperisone HCl; Drug: tolperisone HCl; Drug: tolperisone HCl

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Brno, Czech Republic, 65691
    • Annes University Hospital
  • Hradec Kralove, Czech Republic, 50005
    • University Hospital Hradec Kralove
  • Plzen, Czech Republic, 30460
    • University Hospital Plzen
  • Praha, Czech Republic, 15006
    • University Hospital Motol
• Germany
  • Bad Saarow, Germany, 15526
    • Facharzt fur Neurologie
  • Berlin, Germany, 12555
    • Facharztin fur Neurologie und Psychiatrie
  • Berlin, Germany, 13053
    • Facharzt fur Neurologie und Psychiatrie
  • Berlin, Germany, D-13156
    • Private Practice
  • Bochum, Germany, 44805
    • Neurological practice
  • Dusseldorf, Germany, 40212
    • Neuro-Consil Gmbh
  • Graefelfing, Germany, 82166
    • X-pert-med GmbH
  • Hamburg, Germany, D022417
    • Asklepios Klinik Nord-Heidberg
  • Koln, Germany, 50767
    • Neurological practice
• Russian Federation
  • Nizhniy Novgorod, Russian Federation, 603076
    • City Hospital #33
  • Nizhniy Novgorod, Russian Federation, 603126
    • Regional Clinical Hospital named Semashko
  • St. Petersburg, Russian Federation, 194291
    • Institute of Human Brain
  • St. Petersburg, Russian Federation, 197376
    • Leningrad Regional Clinical Hospital
  • St. Petersburg, Russian Federation, 198510
    • Nikolaevskaya Hospital, Complex Rehabilitation Department
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia Institute of Neurology
  • Nis, Serbia, 18000
    • Clinical Center Nis Clinic of Neurology
• Ukraine
  • Ivano-Frankivsk, Ukraine, 76008
    • Ivano-Frankivsk Regional Clinical Hospital
  • Kharkiv, Ukraine, 61018
    • Central Clinical Hospital Ukrzalinznytsi (Dept. Neur. No. 1)
  • Kharkiv, Ukraine, 61018
    • Central Clinical Hospital Ukrzalinznytsi (Dept. Neur. No. 3)
  • Kharkiv, Ukraine, 61068
    • Institute of Neurology, Psychiatry and Narcology of AMS of Ukraine
  • Kyiv, Ukraine, 03115
    • Institute of Clinical Radiology of the Scientific Centre of Radiation Medicine of the AMS of Ukraine
  • Odesa, Ukraine, 65014
    • Odesa Regional Psychoneurological Dispensary
  • Simferopol, Ukraine, 95017
    • M.O.Semashko Republican Clinical Hospital
  • Uzhorod, Ukraine, 88018
    • Uzhgorod Regional Centre of Neurosurgery and Neurology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; AV650 low dose	Drug: tolperisone HCl; 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; Drug: tolperisone HCl; 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; Drug: tolperisone HCl; 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
Experimental: 2; AV650 high dose	Drug: tolperisone HCl; 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; Drug: tolperisone HCl; 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; Drug: tolperisone HCl; 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
Experimental: 3; Placebo	Drug: tolperisone HCl; 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; Drug: tolperisone HCl; 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; Drug: tolperisone HCl; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Avigen
• Investigators: Study Director: Glenn Morrison, MSc, PhD, Avigen, Inc.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: September 18, 2007
• First Submitted That Met QC Criteria: September 18, 2007
• First Posted (Estimate): September 20, 2007

Study Record Updates

• Last Update Posted (Estimate): November 4, 2008
• Last Update Submitted That Met QC Criteria: November 3, 2008
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: Multiple sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Multiple Sclerosis; Sclerosis; Muscle Spasticity; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Muscle Relaxants, Central; Tolperisone
• Other Study ID Numbers: AV650-018