Cyclobenzaprine Extended Release (ER) for Fibromyalgia
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 |
---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: cyclobenzaprine ER
|
Drug: cyclobenzaprine ER (AMRIX)
active drug
Other Names:
|
Placebo Comparator: placebo
|
Drug: placebo
matching placebo for AMRIX
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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
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
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Report that pain is a key distressing symptom of their FM
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Have a score of > 4 on the Visual Analogue Pain Scale (VAPS)
Exclusion Criteria: Subjects cannot
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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)
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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
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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)
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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.- amrixfm001
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
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 |
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 |
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
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 |
schwartt@upstate.edu |
- amrixfm001