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

NCT00532532 | Terminated Phase 2

• 1 other identifier: AV650-018
• Study Type: interventional
• Target: 150
• Locations: 5 countries
• Sites: 28

Brief Summary

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

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

Conditions

Muscle Spasticity

Keywords

Multiple sclerosis

Outcome Measures

Primary Outcomes (1)

• To determine the long-term safety and tolerability of AV650 (tolperisone HCl) in subjects with spasticity associated with MS

  38 weeks

Secondary Outcomes (1)

• 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

Study Arms (3)

1

EXPERIMENTAL

AV650 low dose

Drug: tolperisone HCl

2

EXPERIMENTAL

AV650 high dose

Drug: tolperisone HCl

3

EXPERIMENTAL

Placebo

Drug: tolperisone HCl

Interventions

tolperisone HCl DRUG

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

1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Avigen: lead

Study Sites (28)

Annes University Hospital

Brno, 65691, Czechia

Location

University Hospital Hradec Kralove

Hradec Králové, 50005, Czechia

Location

University Hospital Plzen

Pilsen, 30460, Czechia

Location

University Hospital Motol

Prague, 15006, Czechia

Location

Facharzt fur Neurologie

Bad Saarow, 15526, Germany

Location

Facharztin fur Neurologie und Psychiatrie

Berlin, 12555, Germany

Location

Facharzt fur Neurologie und Psychiatrie

Berlin, 13053, Germany

Location

Private practice

Berlin, D-13156, Germany

Location

Neurological practice

Bochum, 44805, Germany

Location

Neurological practice

Cologne, 50767, Germany

Location

Neuro-Consil GmbH

Düsseldorf, 40212, Germany

Location

X-pert-med GmbH

Gräfelfing, 82166, Germany

Location

Asklepios Klinik Nord-Heidberg

Hamburg, D022417, Germany

Location

City Hospital #33

Nizhny Novgorod, 603076, Russia

Location

Regional Clinical Hospital named Semashko

Nizhny Novgorod, 603126, Russia

Location

Institute of Human Brain

Saint Petersburg, 194291, Russia

Location

Leningrad Regional Clinical Hospital

Saint Petersburg, 197376, Russia

Location

Nikolaevskaya Hospital, Complex Rehabilitation Department

Saint Petersburg, 198510, Russia

Location

Clinical Center of Serbia Institute of Neurology

Belgrade, 11000, Serbia

Location

Clinical Center Nis Clinic of Neurology

Niš, 18000, Serbia

Location

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, 76008, Ukraine

Location

Central Clinical Hospital Ukrzalinznytsi (Dept. Neur. No. 1)

Kharkiv, 61018, Ukraine

Location

Central Clinical Hospital Ukrzalinznytsi (Dept. Neur. No. 3)

Kharkiv, 61018, Ukraine

Location

Institute of Neurology, Psychiatry and Narcology of AMS of Ukraine

Kharkiv, 61068, Ukraine

Location

Institute of Clinical Radiology of the Scientific Centre of Radiation Medicine of the AMS of Ukraine

Kyiv, 03115, Ukraine

Location

Odesa Regional Psychoneurological Dispensary

Odesa, 65014, Ukraine

Location

M.O.Semashko Republican Clinical Hospital

Simferopol, 95017, Ukraine

Location

Uzhgorod Regional Centre of Neurosurgery and Neurology

Uzhhorod, 88018, Ukraine

Location

MeSH Terms

Conditions

Muscle Spasticity; Multiple Sclerosis

Interventions

Tolperisone

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Propiophenones; Ketones; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Glenn Morrison, MSc, PhD

  Avigen, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: September 18, 2007
• First Posted: September 20, 2007
• Study Start: September 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: November 1, 2008
• Last Updated: November 4, 2008

Record last verified: 2008-11

Locations

CZ (4); DE (9); SE (2); UA (8); RU (5)