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

This study has been terminated.
Sponsor:
Information provided by:
Avigen
ClinicalTrials.gov Identifier:
NCT00532532
First received: September 18, 2007
Last updated: November 3, 2008
Last verified: November 2008
  Purpose

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).

Condition Intervention Phase
Muscle Spasticity
Drug: tolperisone HCl
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Avigen:

Primary Outcome Measures:
  • To determine the long-term safety and tolerability of AV650 (tolperisone HCl) in subjects with spasticity associated with MS [ Time Frame: 38 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 38 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: September 2007
Study Completion Date: November 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Experimental: 2
AV650 high dose
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
Experimental: 3
Placebo
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00532532

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

No publications provided

Responsible Party: Glenn Morrison, Ph.D., Avigen, Inc.
ClinicalTrials.gov Identifier: NCT00532532     History of Changes
Other Study ID Numbers: AV650-018
Study First Received: September 18, 2007
Last Updated: November 3, 2008
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Czech Republic: State Institute for Drug Control
Russia: Ministry of Health of the Russian Federation
Ukraine: State Pharmacological Center - Ministry of Health

Keywords provided by Avigen:
Multiple sclerosis

Additional relevant MeSH terms:
Muscle Spasticity
Multiple Sclerosis
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Muscle Hypertonia
Muscular Diseases
Musculoskeletal Diseases
Nervous System Diseases
Neurologic Manifestations
Neuromuscular Manifestations
Pathologic Processes
Signs and Symptoms
Tolperisone
Central Nervous System Agents
Muscle Relaxants, Central
Neuromuscular Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014