Clinical trial NCT00532532: Safety and Preliminary Effectiveness of AV650 in Patients With Spasticity Associated With Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Muscle Spasticity
Keywords: Multiple sclerosis
Lead sponsor: Avigen
Sponsor class: INDUSTRY
First posted: 2007-09-20
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. 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).


Eligibility 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

Primary outcomes:
measure: To determine the long-term safety and tolerability of AV650 (tolperisone HCl) in subjects with spasticity associated with MS
timeFrame: 38 weeks
Secondary outcomes:
measure: 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
timeFrame: 38 weeks
Other outcomes:
Locations:
city: Brno
country: Czech Republic
facility: Annes University Hospital
city: Hradec Kralove
country: Czech Republic
facility: University Hospital Hradec Kralove
city: Plzen
country: Czech Republic
facility: University Hospital Plzen
city: Praha
country: Czech Republic
facility: University Hospital Motol
city: Bad Saarow
country: Germany
facility: Facharzt fur Neurologie
city: Berlin
country: Germany
facility: Facharztin fur Neurologie und Psychiatrie
city: Berlin
country: Germany
facility: Facharzt fur Neurologie und Psychiatrie
city: Berlin
country: Germany
facility: Private practice
city: Bochum
country: Germany
facility: Neurological practice
city: Dusseldorf
country: Germany
facility: Neuro-Consil GmbH
city: Graefelfing
country: Germany
facility: X-pert-med GmbH
city: Hamburg
country: Germany
facility: Asklepios Klinik Nord-Heidberg
city: Koln
country: Germany
facility: Neurological practice
city: Nizhniy Novgorod
country: Russian Federation
facility: City Hospital #33
city: Nizhniy Novgorod
country: Russian Federation
facility: Regional Clinical Hospital named Semashko
city: St. Petersburg
country: Russian Federation
facility: Institute of Human Brain
city: St. Petersburg
country: Russian Federation
facility: Leningrad Regional Clinical Hospital
city: St. Petersburg
country: Russian Federation
facility: Nikolaevskaya Hospital, Complex Rehabilitation Department
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia Institute of Neurology
city: Nis
country: Serbia
facility: Clinical Center Nis Clinic of Neurology
city: Ivano-Frankivsk
country: Ukraine
facility: Ivano-Frankivsk Regional Clinical Hospital
city: Kharkiv
country: Ukraine
facility: Central Clinical Hospital Ukrzalinznytsi (Dept. Neur. No. 1)
city: Kharkiv
country: Ukraine
facility: Central Clinical Hospital Ukrzalinznytsi (Dept. Neur. No. 3)
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology of AMS of Ukraine
city: Kyiv
country: Ukraine
facility: Institute of Clinical Radiology of the Scientific Centre of Radiation Medicine of the AMS of Ukraine
city: Odesa
country: Ukraine
facility: Odesa Regional Psychoneurological Dispensary
city: Simferopol
country: Ukraine
facility: M.O.Semashko Republican Clinical Hospital
city: Uzhorod
country: Ukraine
facility: Uzhgorod Regional Centre of Neurosurgery and Neurology
Study officials:
affiliation: Avigen, Inc.
name: Glenn Morrison, MSc, PhD
role: STUDY_DIRECTOR
References: