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

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

A drug called AV650 (tolperisone HCl) will be given to patients who have spasticity following a spinal cord injury. This study has three purposes:

1. To determine whether AV650 is safe for patients with spinal cord injury;
2. To assess what the body does with AV650 once it is ingested; and,
3. To gather some early evidence as to whether AV650 is effective in treating spasticity in patients with spinal cord injury.

Study Overview

• Status: Terminated
• Conditions: Muscle Spasticity
• Intervention / Treatment: Drug: tolperisone HCl (AV650); Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Winnipeg, Quebec, Canada, R3A 1M4
      • Rehabilitation Hospital Health Sciences Centre
• United States
  • California
    • Pasadena, California, United States, 91106
      • Southern California Clinical Research, Inc.
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Shepherd Center, Inc.
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Internal Center for Spinal Cord Injury Kennedy Kreiger Institute
    • Baltimore, Maryland, United States, 21207
      • Kernan Orthopaedics & Rehab. Hospital
  • New Jersey
    • West Orange, New Jersey, United States, 07052
      • Kessler Institute for Rehab.
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Rehabilitation
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson Medical College of Thomas Jefferson University
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire Veterans Affairs Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Avigen
• Investigators: Principal Investigator: Ralph J Marino, MD, Thomas Jefferson University

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: September 14, 2007
• First Submitted That Met QC Criteria: September 17, 2007
• First Posted (Estimate): September 18, 2007

Study Record Updates

• Last Update Posted (Estimate): November 4, 2008
• Last Update Submitted That Met QC Criteria: November 3, 2008
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: Spinal cord injury
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Wounds and Injuries; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Trauma, Nervous System; Spinal Cord Diseases; Muscle Hypertonia; Spinal Cord Injuries; Muscle Spasticity; Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Muscle Relaxants, Central; Tolperisone
• Other Study ID Numbers: AV650-014