Cyclobenzaprine Extended Release (ER) for Fibromyalgia

Sponsor
State University of New York - Upstate Medical University (Other)
Overall Status
Terminated
CT.gov ID
NCT01041495
Collaborator
Cephalon (Industry)
37
1
2
45
0.8

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: cyclobenzaprine ER (AMRIX)
  • Drug: placebo
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
37 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, 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
Study Start Date :
Jun 1, 2009
Actual Primary Completion Date :
Mar 1, 2013
Actual Study Completion Date :
Mar 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: cyclobenzaprine ER

Drug: cyclobenzaprine ER (AMRIX)
active drug
Other Names:
  • AMRIX
  • Placebo Comparator: placebo

    Drug: placebo
    matching placebo for AMRIX

    Outcome Measures

    Primary Outcome Measures

    1. Visual Analogue Pain Scale at 8 Weeks Post Treatment [8 weeks]

      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

    Secondary Outcome Measures

    1. Brief Fatigue Inventory at 8 Weeks Post Treatment [baseline to 8 weeks]

      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

    2. Fibromyalgia Impact Questionnaire Scores at 8 Weeks Post Treatment [from baseline to 8 weeks]

      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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    Site City State Country Postal Code
    1 SUNY Upstate Medical University Syracuse New York United States 13210

    Sponsors and Collaborators

    • State University of New York - Upstate Medical University
    • Cephalon

    Investigators

    • Principal Investigator: thomas l schwartz, md, SUNY Upstate

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Thomas L. Schwartz, M.D., Assoc Professor, State University of New York - Upstate Medical University
    ClinicalTrials.gov Identifier:
    NCT01041495
    Other Study ID Numbers:
    • amrixfm001
    First Posted:
    Dec 31, 2009
    Last Update Posted:
    Oct 6, 2021
    Last Verified:
    Oct 1, 2021
    Keywords provided by Thomas L. Schwartz, M.D., Assoc Professor, State University of New York - Upstate Medical University
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details radio and billboard ads were used to recruit subjects who were then screened a a psychiatric based practice
    Pre-assignment Detail subjects had to meet eligibility criteria
    Arm/Group Title Cyclobenzaprine ER Placebo
    Arm/Group Description active muscle relaxant medication matching placebo
    Period Title: Overall Study
    STARTED 16 12
    COMPLETED 12 5
    NOT COMPLETED 4 7

    Baseline Characteristics

    Arm/Group Title Cyclobenzaprine ER Placebo Total
    Arm/Group Description Total of all reporting groups
    Overall Participants 16 12 28
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    16
    100%
    12
    100%
    28
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    15
    93.8%
    10
    83.3%
    25
    89.3%
    Male
    1
    6.3%
    2
    16.7%
    3
    10.7%
    Region of Enrollment (participants) [Number]
    United States
    16
    100%
    12
    100%
    28
    100%

    Outcome Measures

    1. Primary Outcome
    Title Visual Analogue Pain Scale at 8 Weeks Post Treatment
    Description 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
    Time Frame 8 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cyclobenzaprine ER Placebo
    Arm/Group Description cyclobenzaprine ER (AMRIX): active drug placebo: matching placebo for AMRIX
    Measure Participants 16 12
    Mean (Full Range) [units on a scale]
    4.8
    5.7
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cyclobenzaprine ER, Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value .869
    Comments P values below 0.05 were considered statistically significant
    Method t-test, 2 sided
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value .869
    Confidence Interval (2-Sided) 95%
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Brief Fatigue Inventory at 8 Weeks Post Treatment
    Description 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
    Time Frame baseline to 8 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cyclobenzaprine ER Placebo
    Arm/Group Description cyclobenzaprine ER (AMRIX): active drug placebo: matching placebo for AMRIX
    Measure Participants 16 12
    Mean (Full Range) [score on a scale]
    4.7
    4.8
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cyclobenzaprine ER, Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value .486
    Comments
    Method t-test, 2 sided
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cyclobenzaprine ER, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value .486
    Comments
    Method t-test, 1 sided
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Fibromyalgia Impact Questionnaire Scores at 8 Weeks Post Treatment
    Description 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
    Time Frame from baseline to 8 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Cyclobenzaprine ER Placebo
    Arm/Group Description cyclobenzaprine ER (AMRIX): active drug placebo: matching placebo for AMRIX
    Measure Participants 16 12
    Mean (Full Range) [units on a scale]
    59
    51
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Cyclobenzaprine ER, Placebo
    Comments
    Type of Statistical Test Superiority or Other (legacy)
    Comments
    Statistical Test of Hypothesis p-Value .869
    Comments
    Method t-test, 2 sided
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 17
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Cyclobenzaprine ER, Placebo
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value .275
    Comments
    Method t-test, 1 sided
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 17
    Confidence Interval (2-Sided) %
    to
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame During acute study (8 Weeks)
    Adverse Event Reporting Description
    Arm/Group Title Cyclobenzaprine ER Placebo
    Arm/Group Description active drug inactive placebo matching
    All Cause Mortality
    Cyclobenzaprine ER Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Cyclobenzaprine ER Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/16 (0%) 0/12 (0%)
    Other (Not Including Serious) Adverse Events
    Cyclobenzaprine ER Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/16 (12.5%) 1/12 (8.3%)
    Endocrine disorders
    glucosemia 0/16 (0%) 1/12 (8.3%)
    General disorders
    Fatigue 1/16 (6.3%) 0/12 (0%)
    dizziness 1/16 (6.3%) 0/12 (0%)

    Limitations/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

    More Information

    Certain Agreements

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

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title thomas schwartz
    Organization SUNY Upstate MEdical Univ
    Phone 3154643166
    Email schwartt@upstate.edu
    Responsible Party:
    Thomas L. Schwartz, M.D., Assoc Professor, State University of New York - Upstate Medical University
    ClinicalTrials.gov Identifier:
    NCT01041495
    Other Study ID Numbers:
    • amrixfm001
    First Posted:
    Dec 31, 2009
    Last Update Posted:
    Oct 6, 2021
    Last Verified:
    Oct 1, 2021