Cyclobenzaprine Extended Release (ER) for Fibromyalgia

NCT01041495 | Terminated Phase 4 Results

• 1 other identifier: amrixfm001
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Fibromyalgia; Pain; Sleep; Fatigue

Keywords

fibromyalgia; Pain; Sleep; Fatigue

Outcome Measures

Primary Outcomes (1)

• Visual Analogue Pain Scale at 8 Weeks Post Treatment

  Visual Analogue Pain Scale -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. Higher scores are worse

  8 weeks

Secondary Outcomes (2)

• Brief Fatigue Inventory at 8 Weeks Post Treatment

  baseline to 8 weeks

• Fibromyalgia Impact Questionnaire Scores at 8 Weeks Post Treatment

  from baseline to 8 weeks

Study Arms (2)

cyclobenzaprine ER

EXPERIMENTAL

active drug

Drug: cyclobenzaprine ER (AMRIX)

placebo

PLACEBO COMPARATOR

placebo

Drug: placebo

Interventions

cyclobenzaprine ER (AMRIX) DRUG

active drug

Also known as: AMRIX

cyclobenzaprine ER

placebo DRUG

matching placebo for cyclobenzaprine ER (AMRIX)

Also known as: matching placebo for cyclobenzaprine ER (AMRIX)

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• State University of New York - Upstate Medical University: lead
• Cephalon, Inc.: collaborator

Study Sites (1)

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

MeSH Terms

Conditions

Fibromyalgia; Pain; Fatigue

Interventions

cyclobenzaprine

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Recruitment was halted as advertisements failed to bring in enough subjects.There were 37 enrollees: some screen failed, never started protocol,lost to follow up, some data not analyzable affording 28 subjects to be included

Results Point of Contact

• Title: thomas schwartz
• Organization: SUNY Upstate MEdical Univ

schwartt@upstate.edu

3154643166

Study Officials

• thomas l schwartz, md

  SUNY Upstate

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc Professor

Study Record Dates

• First Submitted: June 29, 2009
• First Posted: December 31, 2009
• Study Start: June 1, 2009
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: November 27, 2024
• Results First Posted: October 6, 2021

Record last verified: 2024-11

Locations

US (1)