STAR: Tolperisone in Acute Muscle Spasm of the Back

• Sponsor: Neurana Pharmaceuticals, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03802565
• Collaborator: (none)
• Enrollment: 415
• Locations: 43
• Arms: 5
• Actual Duration (Months): 5.3
• Patients Per Site: 9.7
• Patients Per Site Per Month: 1.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Back Pain; Acute Pain; Back Spasm Upper Back; Back Strain; Muscle Cramp; Muscle Spasm; Low Back Pain	Drug: Tolperisone; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 415 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Dose Ranging Study of Tolperisone in Acute Muscle Spasm of the Back
• Actual Study Start Date: Feb 1, 2019
• Actual Primary Completion Date: Jun 28, 2019
• Actual Study Completion Date: Jul 12, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tolperisone 50 mg TID (150 mg/day)	Drug: Tolperisone; TID
Experimental: Tolperisone 100 mg TID (300 mg/day)	Drug: Tolperisone; TID
Experimental: Tolperisone 150 mg TID (450 mg/day)	Drug: Tolperisone; TID
Experimental: Tolperisone 200 mg TID (600 mg/day)	Drug: Tolperisone; TID
Placebo Comparator: Placebo TID	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. 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."

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tennessee Valley Pain Consultants	Huntsville	Alabama	United States	35801
2	Fiel Family and Sports Medicine	Tempe	Arizona	United States	85283
3	Center of Applied Research	Little Rock	Arkansas	United States	72212
4	Research Center of Fresno	Fresno	California	United States	93702
5	Long Beach Clinical Trials Services, Inc.	Long Beach	California	United States	90806
6	Northern California Research	Sacramento	California	United States	95628
7	Pacific Research Network, LLC	San Diego	California	United States	92103
8	San Diego Sports Medicine	San Diego	California	United States	92120
9	CITrials	Santa Ana	California	United States	92705
10	Riverside Clinical Research	Edgewater	Florida	United States	32132
11	Empirical Research Group	Gainesville	Florida	United States	32653
12	Savin Medical Group	Miami Lakes	Florida	United States	33014
13	LLC Medical Research	Miami	Florida	United States	33126
14	Avail Clinical Research	Orange City	Florida	United States	32763
15	Private Practice	Plantation	Florida	United States	33313
16	NeuroTrials Research, Inc.	Atlanta	Georgia	United States	30342
17	Georgia Institute for Clinical Research	Marietta	Georgia	United States	30060
18	Georgia Clinical Research	Snellville	Georgia	United States	30078
19	MediSphere Medical Research Center	Evansville	Indiana	United States	47714
20	Otrimed Clinical Research	Edgewood	Kentucky	United States	41017
21	Centex Studies, Inc.	Lake Charles	Louisiana	United States	70601
22	Center for Rheumatology and Bone	Wheaton	Maryland	United States	20902
23	Michigan Head Pain and Neurological	Ann Arbor	Michigan	United States	48104
24	Sundance Clinical Research	Saint Louis	Missouri	United States	63141
25	Jubilee Clinical Research	Las Vegas	Nevada	United States	89106
26	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico	United States	87102
27	Upstate Clinical Research Associates	Williamsville	New York	United States	14221
28	Clinical Trials of America	Winston-Salem	North Carolina	United States	27103
29	Sterling Research Group- Springdale	Cincinnati	Ohio	United States	45246
30	Cleveland Clinic	Cleveland	Ohio	United States	44195
31	Center for Providence Health Partners	Dayton	Ohio	United States	45439
32	IPS Research	Oklahoma City	Oklahoma	United States	73103
33	Williamette Valley Clinical Studies	Eugene	Oregon	United States	97404
34	Frontier Clinical Research, Inc.	Smithfield	Pennsylvania	United States	15478
35	Omega Medical Research	Warwick	Rhode Island	United States	02886
36	Health Concepts	Rapid City	South Dakota	United States	57702
37	Inquest Clinical Research	Baytown	Texas	United States	77521
38	DiscoveResearch, Inc.	Bryan	Texas	United States	77802
39	HD Research Corp	Houston	Texas	United States	77004
40	Centex Studies, Inc.	McAllen	Texas	United States	78504
41	ClinRX Research Joseph, Inc.	Plano	Texas	United States	75007
42	Highland Clinical Research	Salt Lake City	Utah	United States	84124
43	Health Research of Hampton Roads, Inc.	Newport News	Virginia	United States	23606

Sponsors and Collaborators

• Neurana Pharmaceuticals, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 2, 2019
• Statistical Analysis Plan - Aug 6, 2019

More Information

Publications

None provided.

• Responsible Party: Neurana Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT03802565
• Other Study ID Numbers: 201
• First Posted: Jan 14, 2019
• Last Update Posted: Feb 1, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Muscle Cramp; Spasm; Hyperkinesis; Back Pain; Low Back Pain; Acute Pain; Tolperisone

Study Results

Participant Flow

Arm/Group Title	Tolperisone 50 mg	Tolperisone 100 mg	Tolperisone 150 mg	Tolperisone 200 mg	Placebo
Arm/Group Description	TID (150 mg/day) Tolperisone: TID	TID (300 mg/day) Tolperisone: TID	TID (450 mg/day) Tolperisone: TID	TID (600 mg/day) Tolperisone: TID	TID Placebo: Placebo
Period Title: Overall Study
STARTED	82	87	83	85	78
COMPLETED	77	83	74	77	72
NOT COMPLETED	5	4	9	8	6

Baseline Characteristics

Arm/Group Title	Tolperisone 50 mg	Tolperisone 100 mg	Tolperisone 150 mg	Tolperisone 200 mg	Placebo	Total
Arm/Group Description	TID (150 mg/day) Tolperisone: TID	TID (300 mg/day) Tolperisone: TID	TID (450 mg/day) Tolperisone: TID	TID (600 mg/day) Tolperisone: TID	TID Placebo: Placebo	Total of all reporting groups
Overall Participants	82	87	83	85	78	415
Age, Customized (years) [Mean (Full Range) ]
Mean (Full Range) [years]	43.5	44.4	44.3	42.0	41.6	43.6
Sex: Female, Male (Count of Participants)
Female	45 54.9%	57 65.5%	41 49.4%	41 48.2%	49 62.8%	233 56.1%
Male	37 45.1%	30 34.5%	42 50.6%	44 51.8%	29 37.2%	182 43.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 15.9%	18 20.7%	22 26.5%	20 23.5%	16 20.5%	89 21.4%
Not Hispanic or Latino	69 84.1%	69 79.3%	61 73.5%	65 76.5%	62 79.5%	326 78.6%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.2%	0 0%	1 1.2%	0 0%	1 1.3%	3 0.7%
Asian	1 1.2%	4 4.6%	2 2.4%	4 4.7%	3 3.8%	14 3.4%
Native Hawaiian or Other Pacific Islander	1 1.2%	1 1.1%	1 1.2%	0 0%	0 0%	3 0.7%
Black or African American	29 35.4%	32 36.8%	29 34.9%	35 41.2%	29 37.2%	154 37.1%
White	50 61%	50 57.5%	49 59%	45 52.9%	42 53.8%	236 56.9%
More than one race	0 0%	0 0%	1 1.2%	0 0%	3 3.8%	4 1%
Unknown or Not Reported	0 0%	0 0%	0 0%	1 1.2%	0 0%	1 0.2%
Body Mass Index (kilogram/meter^2) [Mean (Full Range) ]
Mean (Full Range) [kilogram/meter^2]	28.23	28.48	28.34	28.45	28.53	28.38

Outcome Measures

1. Primary Outcome

Title	Mean Effect Size in Subjected-Rated Pain
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Tolperisone 50 mg	Tolperisone 100 mg	Tolperisone 150 mg	Tolperisone 200 mg	Placebo
Arm/Group Description	TID (150 mg/day) Tolperisone: TID	TID (300 mg/day) Tolperisone: TID	TID (450 mg/day) Tolperisone: TID	TID (600 mg/day) Tolperisone: TID	TID Placebo: Placebo
Measure Participants	82	87	83	85	78
Mean (95% Confidence Interval) [score on a scale]	-4.2	-4.0	-3.7	-4.4	-3.5

Adverse Events

Time Frame	First Dose, Day 1 to Follow-up, Day 28
Arm/Group Title	Tolperisone 50 mg		Tolperisone 100 mg		Tolperisone 150 mg		Tolperisone 200 mg		Placebo
Arm/Group Description	TID (150 mg/day) Tolperisone: TID		TID (300 mg/day) Tolperisone: TID		TID (450 mg/day) Tolperisone: TID		TID (600 mg/day) Tolperisone: TID		TID Placebo: Placebo
All Cause Mortality
	Tolperisone 50 mg		Tolperisone 100 mg		Tolperisone 150 mg		Tolperisone 200 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		0/87 (0%)		0/83 (0%)		0/85 (0%)		0/78 (0%)
Serious Adverse Events
	Tolperisone 50 mg		Tolperisone 100 mg		Tolperisone 150 mg		Tolperisone 200 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/82 (0%)		0/87 (0%)		0/83 (0%)		0/85 (0%)		0/78 (0%)
Other (Not Including Serious) Adverse Events
	Tolperisone 50 mg		Tolperisone 100 mg		Tolperisone 150 mg		Tolperisone 200 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/82 (8.5%)		13/87 (14.9%)		12/83 (14.5%)		14/85 (16.5%)		5/78 (6.4%)
Gastrointestinal disorders
Diarrhoea	2/82 (2.4%)		2/87 (2.3%)		3/83 (3.6%)		1/85 (1.2%)		0/78 (0%)
Nausea	1/82 (1.2%)		1/87 (1.1%)		1/83 (1.2%)		2/85 (2.4%)		0/78 (0%)
Nervous system disorders
Headache	3/82 (3.7%)		5/87 (5.7%)		8/83 (9.6%)		8/85 (9.4%)		3/78 (3.8%)
Dizziness	1/82 (1.2%)		2/87 (2.3%)		0/83 (0%)		2/85 (2.4%)		0/78 (0%)
Somnolence	0/82 (0%)		3/87 (3.4%)		0/83 (0%)		1/85 (1.2%)		2/78 (2.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.