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

Study Overview
=================
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.

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.

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

Conditions
-----------------
Neck Pain, Back Pain, Spasm

Intervention / Treatment
-----------------
* Drug: Cyclobenzaprine HCl
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 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. Is male or female and aged 18 to 50 years, inclusive. 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. Female participants of child-bearing potential must have a negative urine human chorionic gonadotropin (hCG) test result for pregnancy at study entry. 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: 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. Has received any investigational compound within 30 days prior to Screening. 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. 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). Has mild, moderate, severe liver impairment. 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. 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. Takes or took within last 14 days medications, such as: selective serotonin reuptake inhibitors (SSRIs); serotonin norepinephrine reuptake inhibitors (SNRIs); tricyclic antidepressants (TCAs); monoamine oxidase (MAO) inhibitors; tramadol; bupropion; meperidine; verapamil; non-steroid anti-inflammatory drugs (NSAIDs); topical anti-inflammatory medications Has a history or clinical manifestations of significant medical condition, such as: hyperthyroidism; acute recovery phase of myocardial infarction; arrhythmias, heart block or conduction disturbances; congestive heart failure; angle-closure glaucoma; urinary retention; increased intraocular pressure. 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. Has any known condition or disorder that might have affected absorption of the study drug. Has a history of hypersensitivity or allergies to cyclobenzaprine and/or tricyclic antidepressants or any of their components. Has a history of hypersensitivity to any NSAIDs including salicylate sensitivity. Has a history of thrombocytopenia. Has a history of gastro-intestinal bleeding, cerebrovascular bleeding or other bleeding disorders. Had active or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding) Has a history of severe renal impairment Had a major surgery during the 6 months preceding study entry. Has a language barrier or any other problems precluding good communication or cooperation. Has any reason to believe that he/she would not be able to complete the evaluations needed in this study. Has a known history of positive screen for hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV) antibody. Drug abuse in anamnesis.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyclobenzaprine HCl 15 mg<br>Cyclobenzaprine Hydrochloride (HCl) extended-release, 15 mg capsules, orally, once daily for 14 days. | Drug: Cyclobenzaprine HCl<br>* Cyclobenzaprine HCl extended-release capsules<br>* Other names: AMRIX®;|
| Placebo Comparator: Placebo<br>Cyclobenzaprine HCl extended release placebo-matching capsules, orally, once daily for 14 days. | Drug: Placebo<br>* Cyclobenzaprine HCl extended release placebo-matching capsules<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Subject's Rating of Medication Helpfulness Impression on Day 3 of Treatment | 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. | Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Subject's Rating of Medication Helpfulness Impression on Days 7 and 14 of Treatment | 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. | Days 7 and 14 | 
| Percentage of Participants With Physician's Clinical Global Assessment on Day 3 of Treatment | 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. | Day 3 | 
| Percentage of Participants With Physician's Clinical Global Assessment on Days 7 and 15 of Treatment | 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. | Days 7 and 15 | 
| Percentage of Participants With Subject-Rated Global Impression on Days 3, 7, and 14 of Treatment | 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. | Days 3, 7, and 14 | 
| Percentage of Responders on Days 3, 7, and 14 of Treatment | 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. | Days 3, 7, and 14 | 
| Percentage of Participants With Physician Rated Assessment of Presence of Muscle Spasm on Days 3, 7, and 15 of Treatment | 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. | Days 3, 7, and 15 | 
| Percentage of Participants With Physician Rated Assessment of Presence of Local Pain on Days 3, 7, and 15 of Treatment | 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. | Days 3, 7, and 15 | 
| Percentage of Participants With Physician Rated Assessment of Limitation of Range of Motion on Days 3, 7, and 15 of Treatment | 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. | Days 3, 7, and 15 | 
| Percentage of Participants With Physician Rated Assessment of Limitation of Activities of Daily Living on Days 3, 7, and 15 of Treatment | 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. | Days 3, 7, and 15 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Drug therapy