Cyclobenzaprine Extended Release (ER) for Fibromyalgia

Study Overview
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Brief Summary
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Amrix (Cyclobenzaprine hydrochloride Extended release capsules) is approved by the FDA as a muscle relaxant, indicated for the treatment of muscle spasm associated with acute, painful musculoskeletal conditions. Cyclobenzaprine ER (Amrix TM) has a distinct pharmacokinetic profile providing early systemic exposure and consistent plasma concentration over several hours. Overall, a single dose of Amrix 30 mg is similar to that of cyclobenzaprine immediate release 10 mg three times daily. This ER formula should improve compliance, with similar efficacy and possibly less side effects as is often the case with slower release formulations. There are clinical studies showing that cyclobenzaprine can alleviate pain secondary to Fibromyalgia induced muscle tone. This multi-layered evidence base suggests that cyclobenzaprine may be able to alleviate pain in fibromyalgia. Theoretically in fibromyalgia, pain is interpreted centrally and possibly occurs due to said muscle spasm . Cyclobenzaprine may relieve this pain, thus allowing patients to function better during the day and sleep better at night. Cyclobenzaprine has tricyclic antidepressant structure which may also allow pain signal dampening in the spinal cord as well, similar to amitriptyline which is used off-label for neuropathic pain as well. Fibromyalgia (FM) is an illness that may involve medical, rheumatologic, autoimmune, sleep, endocrine and psychiatric pathology. It is a syndrome of recurrent pain at trigger points. Greater than 90% of these patients will report fatigue as a key symptom as well. There are several investigation lines into the treatment of FM induced pain. Exercise, behavioral therapy, amitryptiline, duloxetine, tramadol, sodium oxybate, pregabalin all have randomized trials and almost all focus on pain. There are very few studies evaluating cyclobenzaprine and none studying to Cyclobenzaprine ER formulation. None evaluate pain reduction, sleep and fatigue improvement. Cyclobenzaprine is a drug with minimal adverse effects (dry mouth, dizziness, fatigue, constipation, somnolence, nausea, and dyspepsia). It may have a safer tolerability profile than some of the FM medications noted above. As cyclobenzaprine is often studied and often added as an augmentation agent to patients' regimens who suffer from acute painful musculoskeletal conditions, the authors feel that cyclobenzaprine would also be effective in this population. The authors wish to conduct a study to determine if cyclobenzaprine ER is safe and tolerable in the treatment of FM induced pain, and secondary fatigue and insomnia. This initial study may allow for continued regulatory studies with this product in FM subjects. The authors propose a double-blind placebo controlled study to determine if cyclobenzaprine ER is safe and effective in reversing FM induced pain, and secondary fatigue and insomnia.

Official Title
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An Eight Week, Double-Blind Efficacy Study of Cyclobenzaprine ER (Amrix TM) Augmentation to Alleviate Fibromyalgia Fatigue and Muscle Pain

Conditions
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Fibromyalgia, Pain, Sleep, Fatigue

Intervention / Treatment
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* Drug: cyclobenzaprine ER (AMRIX)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: If possible, 60 subjects will be included in this study. All males/females of any race are eligible if aged between 18 and 65 and Subjects must speak English and have capacity to receive and utilize informed consent Agree to use barrier method contraception or are infertile x 2 years due to medical condition or surgery Have been formally diagnosed by a Board Certified Rheumatologist using the ACR 1990 research criteria for fibromyalgia Report that pain is a key distressing symptom of their FM Have a score of > 4 on the Visual Analogue Pain Scale (VAPS) Exclusion Criteria: Subjects cannot Be pregnant or be attempting to conceive at present (urine bHCG must be negative) Have an active substance abuse problem with last use within the past 90 days (outside of nicotine) Use cardiac QTc prolonging medications i.e., tricyclic antidepressants Use p4502D6 major inhibiting medications as cyclobenzaprine levels may increase Have a known medical condition outside of FM that causes pain, i.e., diabetic neuropathy Have a known medical condition or other medication use that relatively contraindicates cyclobenzaprine use (i.e., hypersensitivity concomitant use of monoamine oxidase (MAO) inhibitors, seizures, known cardiac abnormalities, recent MI. hepatitis, stroke, or psychosis Has a prior history of cyclobenzaprine use and failure (failure due to side effects may be allowed at P.I. discretion) Be receiving daytime/nighttime sedating medication with clear chronological impact on fatigue UNLESS fatigue predates sedating medication or said medication has been steadily dosed > 4 weeks Other medications known to alleviate pain (i.e., Gabapentin, Pregabalin, Amitryptiline, Duloxetine,Venlafaxine, Carbamazepine, Tramadol, etc) unless they have been at steady dose more than 6 weeks

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cyclobenzaprine ER<br> | Drug: cyclobenzaprine ER (AMRIX)<br>* active drug<br>* Other names: AMRIX;|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* matching placebo for AMRIX<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analogue Pain Scale at 8 Weeks Post Treatment | Change in baseline subjective pain based on a 10 point scale (1= no pain, 10 = severe pain) from baseline (T=Zero, prior to drug/placebo treatment) to week 8 | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Fatigue Inventory at 8 Weeks Post Treatment | Change in baseline subjective fatigue based on this scale (1= no fatigue, 10 = severe fatigue) from baseline (T=Zero, prior to drug/placebo treatment) to week 8 | baseline to 8 weeks | 
| Fibromyalgia Impact Questionnaire Scores at 8 Weeks Post Treatment | Change in baseline subjective fibromyalgia symptoms based on a 100 point scale (0 = no fibromyalgia or minimum score, 100 = severe fibromyalgia and maximal score) from baseline (T=Zero, prior to drug/placebo treatment) to week 8 | from baseline to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibromyalgia, Pain, Sleep, Fatigue