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

Sponsor

Avigen (Industry)

Overall Status

Terminated

CT.gov ID

NCT00532532

Collaborator

(none)

150

Enrollment

Locations

Arms

Duration (Months)

5.4

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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:

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

Condition or Disease	Intervention/Treatment	Phase
Muscle Spasticity	Drug: tolperisone HCl Drug: tolperisone HCl Drug: tolperisone HCl	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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

Study Start Date :

Sep 1, 2007

Actual Primary Completion Date :

Sep 1, 2008

Actual Study Completion Date :

Nov 1, 2008

Arms and Interventions

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
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

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

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

Outcome Measures

Primary Outcome Measures

To determine the long-term safety and tolerability of AV650 (tolperisone HCl) in subjects with spasticity associated with MS [38 weeks]

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 [38 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

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