Safety and Preliminary Effectiveness of AV650 in Patients With Spasticity Due to Spinal Cord Injury

Study Overview
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Brief Summary
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A drug called AV650 (tolperisone HCl) will be given to patients who have spasticity following a spinal cord injury. This study has three purposes: To determine whether AV650 is safe for patients with spinal cord injury; To assess what the body does with AV650 once it is ingested; and, To gather some early evidence as to whether AV650 is effective in treating spasticity in patients with spinal cord injury.

Official Title
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AV650-014: A Four Week, Prospective, Randomized, Double Blind, Placebo-Controlled Trial to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AV650 in Patients With Spasticity Due to Spinal Cord Injury

Conditions
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Muscle Spasticity

Intervention / Treatment
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* Drug: tolperisone HCl (AV650)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who provide written informed consent. Male or female subjects aged 18 to 70 years. In the judgment of the Principal Investigator, able to comply with protocol requirements. Subjects willing and able to withdraw from other anti-spasmodic/muscle relaxant drugs for at least two weeks before randomization (including but not limited to baclofen, benzodiazepines, clonazepam, clonidine, dantrolene, diazepam, gabapentin, and tizanidine). Neurological level between C-4 and T-12 spinal cord levels. SCI duration of 6 or more months. Muscle tone sufficient to score at least two (2) on the Ashworth Scale for at least one of the following lower muscle groups: ankle plantar flexors (gastrocnemius), knee extensors (quadriceps), knee flexors (hamstrings) and/or hip adductors (adductors) and seven (7) for the most spastic limb. ASIA Impairment Scale Exam score of B, C or D. Female subjects of childbearing potential must be either surgically sterile or using an effective method of contraception. Female subjects of childbearing potential must have a negative urine pregnancy test at baseline (Study Day 0). Exclusion Criteria: Subjects with a known hypersensitivity to lidocaine or non-steroidal analgesics. Subjects with clinically significant cardiovascular, pulmonary, endocrine, hepatic, renal, neurological, metabolic, or psychiatric disease. Any recent history of mental illness, drug addiction, recreational drug use, or alcoholism and/or any similar condition that the investigator feels should prohibit study participation. Any significant illness during the four weeks preceding Study Day 1. History of cancer or inflammatory arthritis of large joints. History of gastric or duodenal ulcer. Concurrent symptomatic urinary tract infections with fever. Severe physical injury, direct impact trauma, or neurological trauma within the last 6 months not including Spinal Cord Injury. ASIA Impairment Scale score of A or E. Uncontrolled hypertension or hypotension. Percussive tenderness of vertebral body or spinous process. Subjects with corrective surgery to or contracture of the measurable hip, knee, or ankle joints. Subjects known to be Hepatitis B or HIV positive. Female subjects who are pregnant or nursing. Subjects who have received an investigational drug within 30 days before Screening visit. Subjects with any documented episodes of seizures. Subjects requiring use of clinically relevant 2C19 or 2D6 inhibitors, or concomitant use of lidocaine. Use of rescue medication(s) within 48 hours of baseline procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: tolperisone HCl (AV650)<br>* One tablet orally three times a day for 28 days<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* One tablet orally three times a day for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety, tolerability and PK profile of AV650 in subjects with spasticity due to spinal cord injury. |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine preliminary efficacy in subjects with spasticity due to SCI |  | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal cord injury