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

Muscle Spasticity Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00532532
• Other study ID #: AV650-018
• Status: Terminated
• Phase: Phase 2
• First received: September 18, 2007
• Last updated: November 3, 2008
• Start date: September 2007
• Est. completion date: November 2008

Study information

• Verified date: November 2008
• Source: Avigen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesCzech Republic: State Institute for Drug ControlRussia: Ministry of Health of the Russian FederationUkraine: State Pharmacological Center - Ministry of Health
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 150
• Est. completion date: November 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Muscle Spasticity

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Czech Republic	Annes University Hospital	Brno
Czech Republic	University Hospital Hradec Kralove	Hradec Kralove
Czech Republic	University Hospital Plzen	Plzen
Czech Republic	University Hospital Motol	Praha
Germany	Facharzt fur Neurologie	Bad Saarow
Germany	Facharzt fur Neurologie und Psychiatrie	Berlin
Germany	Facharztin fur Neurologie und Psychiatrie	Berlin
Germany	Private practice	Berlin
Germany	Neurological practice	Bochum
Germany	Neuro-Consil GmbH	Dusseldorf
Germany	X-pert-med GmbH	Graefelfing
Germany	Asklepios Klinik Nord-Heidberg	Hamburg
Germany	Neurological practice	Koln
Russian Federation	City Hospital #33	Nizhniy Novgorod
Russian Federation	Regional Clinical Hospital named Semashko	Nizhniy Novgorod
Russian Federation	Institute of Human Brain	St. Petersburg
Russian Federation	Leningrad Regional Clinical Hospital	St. Petersburg
Russian Federation	Nikolaevskaya Hospital, Complex Rehabilitation Department	St. Petersburg
Serbia	Clinical Center of Serbia Institute of Neurology	Belgrade
Serbia	Clinical Center Nis Clinic of Neurology	Nis
Ukraine	Ivano-Frankivsk Regional Clinical Hospital	Ivano-Frankivsk
Ukraine	Central Clinical Hospital Ukrzalinznytsi (Dept. Neur. No. 1)	Kharkiv
Ukraine	Central Clinical Hospital Ukrzalinznytsi (Dept. Neur. No. 3)	Kharkiv
Ukraine	Institute of Neurology, Psychiatry and Narcology of AMS of Ukraine	Kharkiv
Ukraine	Institute of Clinical Radiology of the Scientific Centre of Radiation Medicine of the AMS of Ukraine	Kyiv
Ukraine	Odesa Regional Psychoneurological Dispensary	Odesa
Ukraine	M.O.Semashko Republican Clinical Hospital	Simferopol
Ukraine	Uzhgorod Regional Centre of Neurosurgery and Neurology	Uzhorod

Sponsors (1)

Lead Sponsor	Collaborator
Avigen

Countries where clinical trial is conducted

Czech Republic,  Germany,  Russian Federation,  Serbia,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the long-term safety and tolerability of AV650 (tolperisone HCl) in subjects with spasticity associated with MS		38 weeks	Yes
Secondary	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	No