Cyclobenzaprine Extended Release (ER) for Fibromyalgia

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2012 by State University of New York - Upstate Medical University
Sponsor:
Collaborator:
Cephalon
Information provided by (Responsible Party):
Thomas L. Schwartz, M.D., State University of New York - Upstate Medical University
ClinicalTrials.gov Identifier:
NCT01041495
First received: June 29, 2009
Last updated: September 6, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Fibromyalgia
Pain
Sleep
Fatigue
Drug: cyclobenzaprine ER (AMRIX)
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: An Eight Week, Double-Blind Efficacy Study of Cyclobenzaprine ER (Amrix TM) Augmentation to Alleviate Fibromyalgia Fatigue and Muscle Pain

Resource links provided by NLM:


Further study details as provided by State University of New York - Upstate Medical University:

Primary Outcome Measures:
  • Visual Analogue Pain Scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Brief Fatigue Inventory [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Analogue sleep/wakefulness scale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Fibromyalgia Impact Questionnaire [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Sheehan Disability SCale [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Quick Inventory of Depression [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
  • Reported Adverse Effects [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: June 2009
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cyclobenzaprine ER Drug: cyclobenzaprine ER (AMRIX)
active drug
Other Name: AMRIX
Placebo Comparator: placebo Drug: placebo
matching placebo for AMRIX

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01041495

Contacts
Contact: thomas l schwartz, md 3154643166 schwartt@upstate.edu

Locations
United States, New York
SUNY Upstate Medical University Recruiting
Syracuse, New York, United States, 13210
Contact: thomas l schwartz, md    315-464-3166    schwartt@upstate.edu   
Principal Investigator: Thomas L Schwartz, MD         
Sponsors and Collaborators
State University of New York - Upstate Medical University
Cephalon
Investigators
Principal Investigator: thomas l schwartz, md SUNY Upstate
  More Information

No publications provided

Responsible Party: Thomas L. Schwartz, M.D., Assoc Professor, State University of New York - Upstate Medical University
ClinicalTrials.gov Identifier: NCT01041495     History of Changes
Other Study ID Numbers: amrixfm001
Study First Received: June 29, 2009
Last Updated: September 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by State University of New York - Upstate Medical University:
fibromyalgia
Pain
Sleep
Fatigue

Additional relevant MeSH terms:
Fatigue
Fibromyalgia
Myofascial Pain Syndromes
Signs and Symptoms
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Neuromuscular Diseases
Nervous System Diseases
Cyclobenzaprine
Amitriptyline
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Muscle Relaxants, Central
Physiological Effects of Drugs
Neuromuscular Agents
Peripheral Nervous System Agents
Tranquilizing Agents
Central Nervous System Depressants
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Adrenergic Uptake Inhibitors
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014