Acute Pain, Back Pain, Back Spasm Upper Back, Back Strain, Low Back Pain, Muscle Cramp, Muscle Spasm
Conditions
Brief summary
This is a double-blind, randomized, placebo-controlled, parallel group study of the efficacy and safety of tolperisone (a non-opioid) or placebo administered as multiple doses three times a day (TID) in approximately 400 male and female subjects experiencing back pain due to or associated with muscle spasm.
Interventions
DRUGTolperisone
TID
DRUGPlacebo
Placebo
Sponsors
Neurana Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Ambulatory * Current acute back pain and/or stiffness due to acute and painful muscle spasm starting within 7 days prior to study entry and more than 8 weeks after the last episode of acute back pain. * Pain of 4 or more on the subject right now rating of pain intensity Numeric Rating Scale (NRS) scale of 0-10. * Willing to discontinue all medication used for the treatment of pain or muscle spasm on study entry. * Pain localized below the neck and above the inferior gluteal folds. * Body mass index ranging between 18 and 35 kg/m².
Exclusion criteria
* Unwillingness to stop taking pain or antispasmodic medication other than the study medication (specifically opioid use \[e.g., Vicodin\], barbiturates, and cannabis). * Chronic pain for the previous 3 months or longer, on more days than not. * Radicular pain in the lower extremity (i.e. pain radiating below the knee), sciatica pain down the leg, or pain below the knee (indicating a lumber radiculopathy); radicular pain in the upper extremity, radiating into the forearm or hand (indicating a cervical radiculopathy). * Concomitant severe pain in a region other than the back. * Spinal surgery within 1 year of study entry. * Back pain due to major trauma (e.g., motor vehicle accident, fracture of bone) unless resolved for more than 1 year. * Treatment of back pain ongoing with non-pharmacological therapy (e.g., acupuncture, chiropractic adjustment, massage, Transcutaneous Electrical Nerve Stimulation \[TENS\], physiotherapy). * Subjects who test positive for alcohol by breathalyzer test. * Unwilling to stop taking moderate to potent inhibitors of cytochrome P450 (CYP) isozymes CYP2D6 and CYP2C19, which are likely to cause drug interactions with tolperisone HCl (e.g., medications such as paroxetine and fluvoxamine).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Effect Size in Subjected-Rated Pain | Day 1 to Day 14 | Mean effect size between Tolperisone and Placebo of subject-rated pain due to acute back spasm using a Numerical Rating Scale (NRS; 0-10 scale, from no pain to worst possible pain) on Day 14 right now. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Tolperisone 50 mg TID (150 mg/day)
Tolperisone: TID | 82 |
| Tolperisone 100 mg TID (300 mg/day)
Tolperisone: TID | 87 |
| Tolperisone 150 mg TID (450 mg/day)
Tolperisone: TID | 83 |
| Tolperisone 200 mg TID (600 mg/day)
Tolperisone: TID | 85 |
| Placebo TID
Placebo: Placebo | 78 |
| Total | 415 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 | 1 | 1 |
| Overall Study | Elevated Enzymes | 0 | 0 | 0 | 0 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 2 | 1 | 4 | 5 | 1 |
| Overall Study | Subjects Related to Each Other | 1 | 0 | 0 | 2 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 2 | 0 | 1 |
Baseline characteristics
| Characteristic | Tolperisone 50 mg | Tolperisone 100 mg | Tolperisone 150 mg | Tolperisone 200 mg | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Customized | 43.5 years | 44.4 years | 44.3 years | 42.0 years | 41.6 years | 43.6 years |
| Body Mass Index | 28.23 kilogram/meter^2 | 28.48 kilogram/meter^2 | 28.34 kilogram/meter^2 | 28.45 kilogram/meter^2 | 28.53 kilogram/meter^2 | 28.38 kilogram/meter^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 18 Participants | 22 Participants | 20 Participants | 16 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants | 69 Participants | 61 Participants | 65 Participants | 62 Participants | 326 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 2 Participants | 4 Participants | 3 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 32 Participants | 29 Participants | 35 Participants | 29 Participants | 154 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 50 Participants | 50 Participants | 49 Participants | 45 Participants | 42 Participants | 236 Participants |
| Sex: Female, Male Female | 45 Participants | 57 Participants | 41 Participants | 41 Participants | 49 Participants | 233 Participants |
| Sex: Female, Male Male | 37 Participants | 30 Participants | 42 Participants | 44 Participants | 29 Participants | 182 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 82 | 0 / 87 | 0 / 83 | 0 / 85 | 0 / 78 |
| other Total, other adverse events | 7 / 82 | 13 / 87 | 12 / 83 | 14 / 85 | 5 / 78 |
| serious Total, serious adverse events | 0 / 82 | 0 / 87 | 0 / 83 | 0 / 85 | 0 / 78 |
Outcome results
Primary
Mean Effect Size in Subjected-Rated Pain
Mean effect size between Tolperisone and Placebo of subject-rated pain due to acute back spasm using a Numerical Rating Scale (NRS; 0-10 scale, from no pain to worst possible pain) on Day 14 right now.
Time frame: Day 1 to Day 14
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Tolperisone 50 mg | Mean Effect Size in Subjected-Rated Pain | -4.2 score on a scale |
| Tolperisone 100 mg | Mean Effect Size in Subjected-Rated Pain | -4.0 score on a scale |
| Tolperisone 150 mg | Mean Effect Size in Subjected-Rated Pain | -3.7 score on a scale |
| Tolperisone 200 mg | Mean Effect Size in Subjected-Rated Pain | -4.4 score on a scale |
| Placebo | Mean Effect Size in Subjected-Rated Pain | -3.5 score on a scale |