Cyclobenzaprine HCl Extended Release 15 mg Versus Placebo in Treatment of Cervical and/or Lower Back Pain Due to Muscle Spasms of Local Origin

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02814565
• Collaborator: (none)
• Enrollment: 180
• Locations: 10
• Arms: 2
• Actual Duration (Months): 5
• Patients Per Site: 18
• Patients Per Site Per Month: 3.6

Study Details

Study Description

Brief Summary

The purpose of this study was to assess the effect of cyclobenzaprine hydrochloride (HCl) extended release (CER) 15 mg capsule once daily in participants with muscle spasms associated with acute painful musculoskeletal conditions.

Condition or Disease	Intervention/Treatment	Phase
Neck Pain; Back Pain; Spasm	Drug: Cyclobenzaprine HCl; Drug: Placebo	Phase 3

Detailed Description

The drug being tested in this study was cyclobenzaprine hydrochloride (HCl) extended-release (CER). CER was being tested to treat participants who had muscle spasms associated with acute painful musculoskeletal conditions. This study looked at medication helpfulness, relief from muscle spasms and pain, and improvement in range of motion and daily living activities.

The study enrolled 180 participants. Participants were randomly assigned (by chance, like flipping a coin) to one of the two treatment groups which remained undisclosed to the participant and study doctor during the study:

• CER 15 mg

• Placebo (dummy inactive pill) - this was a capsule that looks like the study drug but had no active ingredient

All participants were asked to take one capsule at the same time each day throughout the study.

This multi-center trial was conducted in the Russian Federation. The overall time to participate in this study was up to 45 days. Participants made multiple visits to the clinic, and were contacted by telephone after the last dose of study drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multicenter Trial to Study the Efficacy and Safety of Cyclobenzaprine HCl Extended Release (CER) 15 mg in Subjects With Acute Cervical and/or Lower Back Pain Due to Muscle Spasms of Local Origin
• Actual Study Start Date: Oct 12, 2016
• Actual Primary Completion Date: Feb 10, 2017
• Actual Study Completion Date: Mar 14, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyclobenzaprine HCl 15 mg Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Drug: Cyclobenzaprine HCl; Cyclobenzaprine HCl extended-release capsules; Other Names: Myorix® AMRIX®
Placebo Comparator: Placebo Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.	Drug: Placebo; Cyclobenzaprine HCl extended release placebo-matching capsules

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Subject's Rating of Medication Helpfulness Impression on Day 3 of Treatment [Day 3]

   Participants assessed the study medication helpfulness on a daily basis (in the daily diary), using the following 5-point rating scale: "How would you rate this study medication in improving your condition?" "0 = poor", "1 = fair", "2 = good", "3 = very good", "4 = excellent".

Secondary Outcome Measures

1. Percentage of Participants With Subject's Rating of Medication Helpfulness Impression on Days 7 and 14 of Treatment [Days 7 and 14]

   Participants assessed the study medication helpfulness on a daily basis (in the daily diary), using the following 5-point rating scale: "How would you rate this study medication in improving your condition?" "0 = poor", "1 = fair", "2 = good", "3 = very good", "4 = excellent".

2. Percentage of Participants With Physician's Clinical Global Assessment on Day 3 of Treatment [Day 3]

   The investigator assessed their clinical global impression of change compared to Baseline, based on physical examination, degree of muscle spasm (presence of muscle spasm assessment), reaction to palpation (presence of local pain assessment), limitation of range of motion, and evaluation of the patient's reported functional assessment (limitation of activities of daily living assessment). The following 5-point rating scale was used: "1 = worse", "2 = no change", "3 = slight improvement", "4 = moderate improvement", "5 = marked improvement".

3. Percentage of Participants With Physician's Clinical Global Assessment on Days 7 and 15 of Treatment [Days 7 and 15]

   The investigator assessed their clinical global impression of change compared to Baseline, based on physical examination, degree of muscle spasm (presence of muscle spasm assessment), reaction to palpation (presence of local pain assessment), limitation of range of motion, and evaluation of the patient's reported functional assessment (limitation of activities of daily living assessment). The following 5-point rating scale was used: "1 = worse", "2 = no change", "3 = slight improvement", "4 = moderate improvement", "5 = marked improvement".

4. Percentage of Participants With Subject-Rated Global Impression on Days 3, 7, and 14 of Treatment [Days 3, 7, and 14]

   Participants assessed their clinical global impression based on relief from local pain, restriction in activities of daily living, restriction of movement and intensity of local pain on a daily basis. The following 5-point rating scale was used: "1 = worse", "2 = no change", "3 = slight improvement", "4 = moderate improvement", "5 = marked improvement".

5. Percentage of Responders on Days 3, 7, and 14 of Treatment [Days 3, 7, and 14]

   A responder was defined as a participant who had both a rating of either "very good" or "excellent" for the participant's rating of medication helpfulness.

6. Percentage of Participants With Physician Rated Assessment of Presence of Muscle Spasm on Days 3, 7, and 15 of Treatment [Days 3, 7, and 15]

   The investigator assessment based on physical examination, presence of muscle spasm (presence of muscle spasm assessment). The following 5-point rating scale was used: "1 = none", "2 = mild", "3 = moderate", "4 = moderately severe", "5 = severe".

7. Percentage of Participants With Physician Rated Assessment of Presence of Local Pain on Days 3, 7, and 15 of Treatment [Days 3, 7, and 15]

   The investigator assessed local pain based on physical examination, reaction to palpation (presence of local pain assessment). The following 5-point rating scale was used: "1 = none", "2 = mild", "3 = moderate", "4 = moderately severe", "5 = severe".

8. Percentage of Participants With Physician Rated Assessment of Limitation of Range of Motion on Days 3, 7, and 15 of Treatment [Days 3, 7, and 15]

   The investigator assessed limitation of range of motion. The following 5-point rating scale was used: "1 = none", "2 = mild", "3 = moderate", "4 = moderately severe", "5 = severe".

9. Percentage of Participants With Physician Rated Assessment of Limitation of Activities of Daily Living on Days 3, 7, and 15 of Treatment [Days 3, 7, and 15]

   The investigator assessed limitation of activities based on evaluation of the patient's reported functional assessment. The following 5-point rating scale was used: "1 = none", "2 = mild", "3 = moderate", "4 = moderately severe", "5 = severe".

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.

3. Is experiencing for no more than 14 days cervical or lower back pain (as assessed by the participant) due to muscle spasms (confirmed by the physician) associated with acute, painful musculoskeletal conditions.

4. Is male or female and aged 18 to 50 years, inclusive.

5. Female participants require to be either 2 years postmenopausal or surgically sterile by bilateral tubal ligation, hysterectomy, or bilateral oophorectomy, or, if premenopausal, had to be using an approved contraceptive method.

6. Female participants of child-bearing potential must have a negative urine human chorionic gonadotropin (hCG) test result for pregnancy at study entry.

7. After signing the informed consent form, the participant agrees not to make changes to dietary, exercise, or smoking habits and not to enter a weight loss program during his/her participation in the study.

Exclusion Criteria:

1. Has muscular pain secondary to acute trauma or fractures (e.g., due to osteoporosis). Such conditions could have been ruled out based on medical history, x-ray, or physical examination.

2. Has received any investigational compound within 30 days prior to Screening.

3. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 1 month after participating in this study; or intending to donate ova during such time period.

4. Has a history of drug abuse or recent (within the last 12 months) history of excessive alcohol consumption defined as >2 drinks/day (>90 ml of 80 proof alcohol or equivalent).

5. Has mild, moderate, severe liver impairment.

6. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.

7. Takes any concomitant medication including over-the-counter and herbal products for muscle spasms. If a participant is taking such medications, the medications has to be discontinued before starting the study.

8. Takes or took within last 14 days medications, such as:

9. selective serotonin reuptake inhibitors (SSRIs);

10. serotonin norepinephrine reuptake inhibitors (SNRIs);

11. tricyclic antidepressants (TCAs);

12. monoamine oxidase (MAO) inhibitors;

13. tramadol;

14. bupropion;

15. meperidine;

16. verapamil;

17. non-steroid anti-inflammatory drugs (NSAIDs);

18. topical anti-inflammatory medications

19. Has a history or clinical manifestations of significant medical condition, such as:

20. hyperthyroidism;

21. acute recovery phase of myocardial infarction;

22. arrhythmias, heart block or conduction disturbances;

23. congestive heart failure;

24. angle-closure glaucoma;

25. urinary retention;

26. increased intraocular pressure.

27. Has abnormal physical findings or a medical condition that might have placed the participant at risk or interfered with the participant's ability to participate in the study.

28. Has any known condition or disorder that might have affected absorption of the study drug.

29. Has a history of hypersensitivity or allergies to cyclobenzaprine and/or tricyclic antidepressants or any of their components.

30. Has a history of hypersensitivity to any NSAIDs including salicylate sensitivity.

31. Has a history of thrombocytopenia.

32. Has a history of gastro-intestinal bleeding, cerebrovascular bleeding or other bleeding disorders.

33. Had active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding)

34. Has a history of severe renal impairment

35. Had a major surgery during the 6 months preceding study entry.

36. Has a language barrier or any other problems precluding good communication or cooperation.

37. Has any reason to believe that he/she would not be able to complete the evaluations needed in this study.

38. Has a known history of positive screen for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) antibody.

39. Drug abuse in anamnesis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Lipetsk	Lipetsk Region	Russian Federation
2		Saransk	Republic Of Mordovia	Russian Federation
3		Kazan	Republic Of Tatarstan	Russian Federation
4		Ekaterinburg	Sverdlovsk Region	Russian Federation
5		Moscow		Russian Federation
6		Nizhny Novgorod		Russian Federation
7		Novosibirsk		Russian Federation
8		Saint-Petersburg		Russian Federation
9		Tver		Russian Federation
10		Yaroslavl		Russian Federation

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

• Statistical Analysis Plan - May 24, 2017
• Study Protocol - Aug 16, 2016

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02814565
• Other Study ID Numbers: CYC-RR-001; U1111-1162-4846
• First Posted: Jun 27, 2016
• Last Update Posted: Apr 8, 2019
• Last Verified: Jan 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug therapy
• Additional relevant MeSH terms: Spasm; Back Pain; Neck Pain; Low Back Pain; Cyclobenzaprine

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 10 investigative sites in the Russian Federation from 12 October 2016 to 14 March 2017.
Pre-assignment Detail	Participants with a diagnosis of acute cervical and/or lower back pain due to muscle spasms of local origin were enrolled equally in one of two treatment groups: Cyclobenzaprine HCl 15 mg or placebo.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Period Title: Overall Study
STARTED	90	90
COMPLETED	89	88
NOT COMPLETED	1	2

Baseline Characteristics

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo	Total
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.	Total of all reporting groups
Overall Participants	90	90	180
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	33.0 (9.0)	31.5 (9.2)	32.3 (9.1)
Sex: Female, Male (Count of Participants)
Female	48 53.3%	62 68.9%	110 61.1%
Male	42 46.7%	28 31.1%	70 38.9%
Race/Ethnicity, Customized (Count of Participants)
European (Caucasian)	90 100%	90 100%	180 100%
Region of Enrollment (Count of Participants)
Russia	90 100%	90 100%	180 100%
Smoking Status (Count of Participants)
Never smoked	78 86.7%	79 87.8%	157 87.2%
Former smoker	1 1.1%	3 3.3%	4 2.2%
Current smoker	11 12.2%	8 8.9%	19 10.6%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	171.8 (8.2)	169.1 (7.6)	170.5 (8.0)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	71.05 (14.53)	66.22 (13.61)	68.64 (14.25)

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Subject's Rating of Medication Helpfulness Impression on Day 3 of Treatment
Description	Participants assessed the study medication helpfulness on a daily basis (in the daily diary), using the following 5-point rating scale: "How would you rate this study medication in improving your condition?" "0 = poor", "1 = fair", "2 = good", "3 = very good", "4 = excellent".
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

FAS included participants who received at least one dose of investigation product, analyzed according to original treatment assignment.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Measure Participants	90	90
Day 3, 0=poor	20.0 22.2%	28.9 32.1%
Day 3, 1=fair	60.0 66.7%	46.7 51.9%
Day 3, 2=good	16.7 18.6%	22.2 24.7%
Day 3, 3=very good	3.3 3.7%	2.2 2.4%
Day 3, 4=excellent	0.0 0%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	The 2-sample Wilcoxon rank sum test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6179
	Comments
	Method	Wilcoxon Rank Sum test
	Comments

2. Secondary Outcome

Title	Percentage of Participants With Subject's Rating of Medication Helpfulness Impression on Days 7 and 14 of Treatment
Description	Participants assessed the study medication helpfulness on a daily basis (in the daily diary), using the following 5-point rating scale: "How would you rate this study medication in improving your condition?" "0 = poor", "1 = fair", "2 = good", "3 = very good", "4 = excellent".
Time Frame	Days 7 and 14

Outcome Measure Data

Analysis Population Description

FAS included participants who received at least one dose of investigation product, analyzed according to original treatment assignment.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Measure Participants	90	90
Day 7, 0=poor	7.8 8.7%	16.7 18.6%
Day 7, 1=fair	41.1 45.7%	34.4 38.2%
Day 7, 2=good	35.6 39.6%	34.4 38.2%
Day 7, 3=very good	13.3 14.8%	11.1 12.3%
Day 7, 4=excellent	2.2 2.4%	3.3 3.7%
Day 14, 0=poor	8.9 9.9%	14.4 16%
Day 14, 1=fair	25.6 28.4%	25.6 28.4%
Day 14, 2=good	25.6 28.4%	28.9 32.1%
Day 14, 3=very good	22.2 24.7%	20.0 22.2%
Day 14, 4=excellent	17.8 19.8%	11.1 12.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 7. The 2-sample Wilcoxon rank sum test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4338
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 14. The 2-sample Wilcoxon rank sum test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1657
	Comments
	Method	Wilcoxon Rank Sum Test
	Comments

3. Secondary Outcome

Title	Percentage of Participants With Physician's Clinical Global Assessment on Day 3 of Treatment
Description	The investigator assessed their clinical global impression of change compared to Baseline, based on physical examination, degree of muscle spasm (presence of muscle spasm assessment), reaction to palpation (presence of local pain assessment), limitation of range of motion, and evaluation of the patient's reported functional assessment (limitation of activities of daily living assessment). The following 5-point rating scale was used: "1 = worse", "2 = no change", "3 = slight improvement", "4 = moderate improvement", "5 = marked improvement".
Time Frame	Day 3

Outcome Measure Data

Analysis Population Description

FAS included participants who received at least one dose of investigation product, analyzed according to original treatment assignment.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Measure Participants	90	90
Day 3, 1=worse	1.1 1.2%	0.0 0%
Day 3, 2=no change	52.2 58%	68.9 76.6%
Day 3, 3=slight improvement	35.6 39.6%	25.6 28.4%
Day 3, 4=moderate improvement	11.1 12.3%	3.3 3.7%
Day 3, 5=marked improvement	0.0 0%	2.2 2.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0393
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

4. Secondary Outcome

Title	Percentage of Participants With Physician's Clinical Global Assessment on Days 7 and 15 of Treatment
Description	The investigator assessed their clinical global impression of change compared to Baseline, based on physical examination, degree of muscle spasm (presence of muscle spasm assessment), reaction to palpation (presence of local pain assessment), limitation of range of motion, and evaluation of the patient's reported functional assessment (limitation of activities of daily living assessment). The following 5-point rating scale was used: "1 = worse", "2 = no change", "3 = slight improvement", "4 = moderate improvement", "5 = marked improvement".
Time Frame	Days 7 and 15

Outcome Measure Data

Analysis Population Description

FAS included participants who received at least one dose of investigation product, analyzed according to original treatment assignment.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Measure Participants	90	90
Day 7, 1=worse	2.2 2.4%	0.0 0%
Day 7, 2=no change	8.9 9.9%	26.7 29.7%
Day 7, 3=slight improvement	52.2 58%	44.4 49.3%
Day 7, 4=moderate improvement	27.8 30.9%	24.4 27.1%
Day 7, 5=marked improvement	8.9 9.9%	4.4 4.9%
Day 15, 1=worse	1.1 1.2%	1.1 1.2%
Day 15, 2=no change	5.6 6.2%	11.1 12.3%
Day 15, 3=slight improvement	27.8 30.9%	34.4 38.2%
Day 15, 4=moderate improvement	30.0 33.3%	32.2 35.8%
Day 15, 5=marked improvement	35.6 39.6%	21.1 23.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 7. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0330
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 15. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0262
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

5. Secondary Outcome

Title	Percentage of Participants With Subject-Rated Global Impression on Days 3, 7, and 14 of Treatment
Description	Participants assessed their clinical global impression based on relief from local pain, restriction in activities of daily living, restriction of movement and intensity of local pain on a daily basis. The following 5-point rating scale was used: "1 = worse", "2 = no change", "3 = slight improvement", "4 = moderate improvement", "5 = marked improvement".
Time Frame	Days 3, 7, and 14

Outcome Measure Data

Analysis Population Description

FAS included participants who received at least one dose of investigation product, analyzed according to original treatment assignment.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Measure Participants	90	90
Day 3, 1=worse	3.3 3.7%	1.1 1.2%
Day 3, 2=no change	45.6 50.7%	56.7 63%
Day 3, 3=slight improvement	47.8 53.1%	33.3 37%
Day 3, 4=moderate improvement	3.3 3.7%	7.8 8.7%
Day 3, 5=marked improvement	0.0 0%	1.1 1.2%
Day 7, 1=worse	4.4 4.9%	1.1 1.2%
Day 7, 2=no change	13.3 14.8%	25.6 28.4%
Day 7, 3=slight improvement	52.2 58%	43.3 48.1%
Day 7, 4=moderate improvement	22.2 24.7%	25.6 28.4%
Day 7, 5=marked improvement	7.8 8.7%	4.4 4.9%
Day 14, 1=worse	1.1 1.2%	1.1 1.2%
Day 14, 2=no change	14.4 16%	26.7 29.7%
Day 14, 3=slight improvement	24.4 27.1%	20.0 22.2%
Day 14, 4=moderate improvement	27.8 30.9%	28.9 32.1%
Day 14, 5=marked improvement	32.2 35.8%	23.3 25.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 3. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5756
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 7. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4395
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 14. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0905
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

6. Secondary Outcome

Title	Percentage of Responders on Days 3, 7, and 14 of Treatment
Description	A responder was defined as a participant who had both a rating of either "very good" or "excellent" for the participant's rating of medication helpfulness.
Time Frame	Days 3, 7, and 14

Outcome Measure Data

Analysis Population Description

FAS included participants who received at least one dose of investigation product, analyzed according to original treatment assignment.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Measure Participants	90	90
Day 3	3.3 3.7%	2.2 2.4%
Day 7	15.6 17.3%	14.4 16%
Day 14	40.0 44.4%	31.1 34.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 3. A two-tailed Fisher's exact test to compare the number of "responders" between the Placebo and the Cyclobenzaprine HCl 15 mg treatment group to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 7. A two-tailed Fisher's exact test to compare the number of "responders" between the Placebo and the Cyclobenzaprine HCl 15 mg treatment group to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	1.0000
	Comments
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 14. A two-tailed Fisher's exact test to compare the number of "responders" between the Placebo and the Cyclobenzaprine HCl 15 mg treatment group to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2757
	Comments
	Method	Fisher Exact
	Comments

7. Secondary Outcome

Title	Percentage of Participants With Physician Rated Assessment of Presence of Muscle Spasm on Days 3, 7, and 15 of Treatment
Description	The investigator assessment based on physical examination, presence of muscle spasm (presence of muscle spasm assessment). The following 5-point rating scale was used: "1 = none", "2 = mild", "3 = moderate", "4 = moderately severe", "5 = severe".
Time Frame	Days 3, 7, and 15

Outcome Measure Data

Analysis Population Description

FAS included participants who received at least one dose of investigation product, analyzed according to original treatment assignment.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Measure Participants	90	90
Day 3, 1=none	2.2 2.4%	2.2 2.4%
Day 3, 2=mild	27.8 30.9%	21.1 23.4%
Day 3, 3=moderate	62.2 69.1%	66.7 74.1%
Day 3, 4=moderately severe	7.8 8.7%	10.0 11.1%
Day 3, 5=severe	0.0 0%	0.0 0%
Day 7, 1=none	14.4 16%	5.6 6.2%
Day 7, 2=mild	47.8 53.1%	53.3 59.2%
Day 7, 3=moderate	37.8 42%	38.9 43.2%
Day 7, 4=moderately severe	0.0 0%	2.2 2.4%
Day 7, 5=severe	0.0 0%	0.0 0%
Day 15, 1=none	48.9 54.3%	32.2 35.8%
Day 15, 2=mild	37.8 42%	47.8 53.1%
Day 15, 3=moderate	13.3 14.8%	20.0 22.2%
Day 15, 4=moderately severe	0.0 0%	0.0 0%
Day 15, 5=severe	0.0 0%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 3. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3020
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 7. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2367
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 15. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0250
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

8. Secondary Outcome

Title	Percentage of Participants With Physician Rated Assessment of Presence of Local Pain on Days 3, 7, and 15 of Treatment
Description	The investigator assessed local pain based on physical examination, reaction to palpation (presence of local pain assessment). The following 5-point rating scale was used: "1 = none", "2 = mild", "3 = moderate", "4 = moderately severe", "5 = severe".
Time Frame	Days 3, 7, and 15

Outcome Measure Data

Analysis Population Description

FAS included participants who received at least one dose of investigation product, analyzed according to original treatment assignment.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Measure Participants	90	90
Day 3, 1=none	1.1 1.2%	1.1 1.2%
Day 3, 2=mild	24.4 27.1%	21.1 23.4%
Day 3, 3=moderate	66.7 74.1%	66.7 74.1%
Day 3, 4=moderately severe	7.8 8.7%	11.1 12.3%
Day 3, 5=severe	0.0 0%	0.0 0%
Day 7, 1=none	6.7 7.4%	2.2 2.4%
Day 7, 2=mild	55.6 61.8%	50.0 55.6%
Day 7, 3=moderate	36.7 40.8%	46.7 51.9%
Day 7, 4=moderately severe	1.1 1.2%	1.1 1.2%
Day 7, 5=severe	0.0 0%	0.0 0%
Day 15, 1=none	35.6 39.6%	25.6 28.4%
Day 15, 2=mild	51.1 56.8%	50.0 55.6%
Day 15, 3=moderate	12.2 13.6%	24.4 27.1%
Day 15, 4=moderately severe	1.1 1.2%	0.0 0%
Day 15, 5=severe	0.0 0%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 3. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4428
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 7. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1163
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 15. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0489
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

9. Secondary Outcome

Title	Percentage of Participants With Physician Rated Assessment of Limitation of Range of Motion on Days 3, 7, and 15 of Treatment
Description	The investigator assessed limitation of range of motion. The following 5-point rating scale was used: "1 = none", "2 = mild", "3 = moderate", "4 = moderately severe", "5 = severe".
Time Frame	Days 3, 7, and 15

Outcome Measure Data

Analysis Population Description

FAS included participants who received at least one dose of investigation product, analyzed according to original treatment assignment.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Measure Participants	90	90
Day 3, 1=none	6.7 7.4%	4.4 4.9%
Day 3, 2=mild	40.0 44.4%	37.8 42%
Day 3, 3=moderate	47.8 53.1%	52.2 58%
Day 3, 4=moderately severe	5.6 6.2%	5.6 6.2%
Day 3, 5=severe	0.0 0%	0.0 0%
Day 7, 1=none	22.2 24.7%	13.3 14.8%
Day 7, 2=mild	51.1 56.8%	51.1 56.8%
Day 7, 3=moderate	26.7 29.7%	35.6 39.6%
Day 7, 4=moderately severe	0.0 0%	0.0 0%
Day 7, 5=severe	0.0 0%	0.0 0%
Day 15, 1=none	44.4 49.3%	38.9 43.2%
Day 15, 2=mild	48.9 54.3%	47.8 53.1%
Day 15, 3=moderate	6.7 7.4%	13.3 14.8%
Day 15, 4=moderately severe	0.0 0%	0.0 0%
Day 15, 5=severe	0.0 0%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 3. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5275
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 7. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0880
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 15. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2542
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

10. Secondary Outcome

Title	Percentage of Participants With Physician Rated Assessment of Limitation of Activities of Daily Living on Days 3, 7, and 15 of Treatment
Description	The investigator assessed limitation of activities based on evaluation of the patient's reported functional assessment. The following 5-point rating scale was used: "1 = none", "2 = mild", "3 = moderate", "4 = moderately severe", "5 = severe".
Time Frame	Days 3, 7, and 15

Outcome Measure Data

Analysis Population Description

FAS included participants who received at least one dose of investigation product, analyzed according to original treatment assignment.

Arm/Group Title	Cyclobenzaprine HCl 15 mg	Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.	Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
Measure Participants	90	90
Day 3, 1=none	4.4	5.6
Day 3, 2=mild	46.7	50.0
Day 3, 3=moderate	46.7	38.9
Day 3, 4=moderately severe	2.2	5.6
Day 3, 5=severe	0.0	0.0
Day 7, 1=none	18.9	10.0
Day 7, 2=mild	62.2	63.3
Day 7, 3=moderate	17.8	26.7
Day 7, 4=moderately severe	1.1	0.0
Day 7, 5=severe	0.0	0.0
Day 15, 1=none	50.0	41.1
Day 15, 2=mild	45.6	53.3
Day 15, 3=moderate	4.4	5.6
Day 15, 4=moderately severe	0.0	0.0
Day 15, 5=severe	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 3. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6920
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 7. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0749
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Cyclobenzaprine HCl 15 mg, Placebo
	Comments	Day 15. The 2-sample Wilcoxon sum rank test was used to test a null hypothesis of no difference between the treatment groups against a two-sided alternative hypothesis at the 0.05 level of significance.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2371
	Comments
	Method	Wilcoxon Sum Rank Test
	Comments

Adverse Events

Time Frame	First dose of study drug to within 30 days of last dose of study drug (Up to 45 days)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Cyclobenzaprine HCl 15 mg		Placebo
Arm/Group Description	Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days.		Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days.
All Cause Mortality
	Cyclobenzaprine HCl 15 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		0/90 (0%)
Serious Adverse Events
	Cyclobenzaprine HCl 15 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/90 (0%)		0/90 (0%)
Other (Not Including Serious) Adverse Events
	Cyclobenzaprine HCl 15 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/90 (23.3%)		12/90 (13.3%)
Cardiac disorders
Tachycardia	1/90 (1.1%)		0/90 (0%)
Gastrointestinal disorders
Dry mouth	6/90 (6.7%)		1/90 (1.1%)
Flatulence	1/90 (1.1%)		2/90 (2.2%)
Toothache	1/90 (1.1%)		0/90 (0%)
Infections and infestations
Influenza	1/90 (1.1%)		1/90 (1.1%)
Rhinitis	1/90 (1.1%)		0/90 (0%)
Nervous system disorders
Dizziness	1/90 (1.1%)		0/90 (0%)
Dysgeusia	1/90 (1.1%)		0/90 (0%)
Headache	0/90 (0%)		1/90 (1.1%)
Poor quality sleep	1/90 (1.1%)		2/90 (2.2%)
Somnolence	18/90 (20%)		5/90 (5.6%)
Psychiatric disorders
Anxiety	1/90 (1.1%)		0/90 (0%)
Disruptive mood dysregulation disorder	1/90 (1.1%)		0/90 (0%)
Sleep disorder	1/90 (1.1%)		0/90 (0%)
Skin and subcutaneous tissue disorders
Dry skin	0/90 (0%)		1/90 (1.1%)
Rash erythematous	0/90 (0%)		1/90 (1.1%)
Skin exfoliation	0/90 (0%)		1/90 (1.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.