Fibromyalgia
Conditions
Keywords
side effects, safety, efficacy, Gralise, Fibromyalgia, gabapentin
Brief summary
To determine Gralise in treating fibromyalgia pain: * efficacy * safety
Detailed description
Subject must carry a diagnosis of fibromyalgia based on American College of Rheumatology (ACR) criteria for fibromyalgia * Patient may be gaba-analogue (Pregabalin, trade name: lyrica, or Gabapentin, trade name: Neurontin) naïve, or had been on other gaba analogue before, and discontinued for lack of efficacy. * Patient who had allergic reaction or serious adverse reactions will not be included in this study. * Patient will start with starter pack of Gralise and will reach therapeutic dose of 1800 mg per day by end of 2 weeks. * Drug is to be taken with meal, once a day in the evening; once patient has reached the therapeutic dose of 1800 mg, patient will come in for visit, at which point the PI will evaluate the patient and may increase or decrease the dosage, but patient may not increase or decrease the dose of medication at his /her discretion. * During study, patient will have total of 5 visits, 4 of which will be for duration patient will be on Gralise, and the last visit will be for tapering off the medication. * During study, patient is asked keep a paper diary on which patient will record the numeric pain scale from Fibromyalgia, time the medication was taken, dose of medication, and any side effects.
Interventions
DRUGGabapentin ER
Patient who are on gralise will report efficacy by rating his or her pain rating on a digital pain scale (11 points) from 0 to 10 on each scheduled clinical visits, which will be compared to their pain level at baseline. In addition, patients will also record the doses and any adverse effects that might arise during the trial in a diary provided by the study. All information will be recorded in a paper diary that will be followed by coordinator during each follow up visits.
Sponsors
Depomed
The Center for Clinical Research, Winston-Salem, NC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject must be 18 years and older. * Subject carries Fibromyalgia diagnosis based on American College of Rheumatology criteria. * Fibromyalgia patients who are gamma-aminobutyric acid (GABA)-analogue (gabapentin or pregabalin) naïve, or those who have been on gamma-aminobutyric acid (GABA)-analogue, but discontinued due to side effects or having difficulty maintaining dosing schedule due to multiple doses per day, or those who are currently on immediate release gamma-aminobutyric acid-analogue (GABA). * Able to distinguish pain from fibromyalgia and pain from other sources. (subjects with other rheumatic disease or medical conditions that contributed to the symptoms of fibromyalgia will be excluded) * Subject pain scores \>4 on Numeric pain rating scale (NPRS)
Exclusion criteria
* Creatinine clearance of \< 30mg/ml * Pain from Traumatic injury or structural or regional rheumatic disease * Unstable medical or psychiatric illness * Lifetime history of psychosis, hypomania, or mania. * Epilepsy, or dementia * Substance abuse in the last 6 months * Suicidal tendencies * Pregnant or breastfeeding * Not on contraception for those of childbearing age. (Barrier methods, oral contraception, hormone injections, or surgical sterilization) * Subjects who are, in the opinion of the principle investigator, are treatment refractory * Treatment with investigational drug within 30 days of screening. * Concomitant medication exclusions consisted of medications or herbal agents with Central Nervous System (CNS) effects with exception of episodic use of sedating antihistamines * Subject who are on more than one additional class of concomitant fibromyalgia medications i.e. non-selective serotonin reuptake inhibitor (SSRI) antidepressants, topicals, opioids.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numeric Pain Rating System (NPRS) | 15 weeks | Fibromyalgia pain experienced by study subjects will be captured using NPRS at baseline visit, at each follow visits that are scheduled to occur every 4 weeks over 12 weeks of treatment period, and at the end of treatment visit that will occur 3 weeks after treatment period (12 weeks treatment period + 3 weeks = 15 weeks). Any difference in NPRS scores between baseline and any subsequent visits will indicate the magnitude of pain relief as reflected in digital scale of 0-10 (0=no pain, 10=worst pain imaginable). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Medical Outcome Study (MOS) Sleep Questionnaires | 15 weeks | Medical Outcomes Study (MOS) sleep questionnaires to assess how Fibromyalgia impacts patients' sleep in various areas. Specifically, Data reported below measured number of hours subjects spent per night sleeping. MOS sleep questionnaires were assessed at each follow up visits. (visits 1, 2, 3, 4, and 5). |
| Self Reported Side Effects. | 15 Weeks | Side / adverse effects were assessed at each follow up visits and resulted are as follows. |
| Fibromyalgia Impact Questionnaire (FIQ) | 15 weeks. | The Fibromyalgia Impact Questionnaire (FIQ) is an instrument designed to quantitate the overall impact of fibromyalgia over many dimensions (e.g. function, pain level, fatigue, sleep disturbance, psychological distress etc.). It is scored from 0 to 100 with the latter number being the worst case. The average score for patients seen in tertiary care settings is about 50. The FIQ is widely used to assess change in fibromyalgia status. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Patient Global Impression of Change (PGIC) | 15 Weeks. | Patient Global impression of Change (PGIC) is an outcome commonly used measure of the efficacy of treatments. PGIC is a 7 point scale that requires the subjects to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Gralise (Gabapentin ER) This is an open label trial to evaluate the efficacy of Gralise against fibromyalgia pain. If subject is taking gabapentinoids at the time of enrollment, subjects will be required to wash off the medication; otherwise they can start the starter pack for Gralise, and will eventually up titrated to treatment dose of 1800mg with evening meals per day.
Subjects will be followed every 4 weeks for total of 12 weeks. At the end of 12 weeks, subjects will be wash off the Gralise over 2 weeks, and will have a final end of treatment visit at week 15.
Subjects will be asked to rate their pain on numeric pain rating system (NPRS) as primary outcome measure. Subjects will be asked to assess Fibromyalgia Impact Questionnaire (FIQ), Medical Outcome Study (MOS) Sleep questionnaire, and Patient Global Impression of Change (PGIC) as secondary outcome measures.
At each follow up visits, occurrence of adverse events, and changes to concomitant medications were evaluated and recorded. | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 12 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Gralise (Gabapentin ER) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 6 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants |
| Age, Continuous | 55.25 years STANDARD_DEVIATION 10.15 |
| Age of Fibromyalgia Diagnosis | 6.96 years |
| Gabapentinoid (Gabapentin/ pregabalin) Naive Gabapentinoid Naive | 8 participants |
| Gabapentinoid (Gabapentin/ pregabalin) Naive Non-Gabapentinoid naive | 26 participants |
| Number of active medications | 1.3 medications |
| Number of co-morbid conditions | 5.3 co-morbid conditions present |
| Number of past medications | 1.6 medications |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 33 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 10 / 31 |
| serious Total, serious adverse events | 2 / 31 |
Outcome results
Primary
Numeric Pain Rating System (NPRS)
Fibromyalgia pain experienced by study subjects will be captured using NPRS at baseline visit, at each follow visits that are scheduled to occur every 4 weeks over 12 weeks of treatment period, and at the end of treatment visit that will occur 3 weeks after treatment period (12 weeks treatment period + 3 weeks = 15 weeks). Any difference in NPRS scores between baseline and any subsequent visits will indicate the magnitude of pain relief as reflected in digital scale of 0-10 (0=no pain, 10=worst pain imaginable).
Time frame: 15 weeks
Population: All subjects had diagnosis of fibromyalgia and met the inclusion and exclusion criteria.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gralise (Gabapentin ER) | Numeric Pain Rating System (NPRS) | NPRS Baseline (Visit 1) | 7.29 units on a scale | Standard Deviation 1.51 |
| Gralise (Gabapentin ER) | Numeric Pain Rating System (NPRS) | NPRS on Week 4 (Visit 2) | 4.72 units on a scale | Standard Deviation 2.44 |
| Gralise (Gabapentin ER) | Numeric Pain Rating System (NPRS) | NPRS on week 8 (Visit 3) | 3.95 units on a scale | Standard Deviation 2.18 |
| Gralise (Gabapentin ER) | Numeric Pain Rating System (NPRS) | NPRS on Week 12 (Visit 4) | 3.83 units on a scale | Standard Deviation 2.05 |
| Gralise (Gabapentin ER) | Numeric Pain Rating System (NPRS) | NPRS on week 15 (Visit 5) | 6.94 units on a scale | Standard Deviation 2.08 |
Secondary
Fibromyalgia Impact Questionnaire (FIQ)
The Fibromyalgia Impact Questionnaire (FIQ) is an instrument designed to quantitate the overall impact of fibromyalgia over many dimensions (e.g. function, pain level, fatigue, sleep disturbance, psychological distress etc.). It is scored from 0 to 100 with the latter number being the worst case. The average score for patients seen in tertiary care settings is about 50. The FIQ is widely used to assess change in fibromyalgia status.
Time frame: 15 weeks.
Population: FM patients who took study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gralise (Gabapentin ER) | Fibromyalgia Impact Questionnaire (FIQ) | FIQ Week 8 | 40.79 units on a scale | Standard Deviation 20.41 |
| Gralise (Gabapentin ER) | Fibromyalgia Impact Questionnaire (FIQ) | FIQ Week 12 | 39.27 units on a scale | Standard Deviation 21.37 |
| Gralise (Gabapentin ER) | Fibromyalgia Impact Questionnaire (FIQ) | FIQ Week 15 | 61.86 units on a scale | Standard Deviation 18.67 |
| Gralise (Gabapentin ER) | Fibromyalgia Impact Questionnaire (FIQ) | FIQ Baseline | 71.04 units on a scale | Standard Deviation 12.84 |
| Gralise (Gabapentin ER) | Fibromyalgia Impact Questionnaire (FIQ) | FIQ Week 4 | 41.82 units on a scale | Standard Deviation 19.57 |
Secondary
Medical Outcome Study (MOS) Sleep Questionnaires
Medical Outcomes Study (MOS) sleep questionnaires to assess how Fibromyalgia impacts patients' sleep in various areas. Specifically, Data reported below measured number of hours subjects spent per night sleeping. MOS sleep questionnaires were assessed at each follow up visits. (visits 1, 2, 3, 4, and 5).
Time frame: 15 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gralise (Gabapentin ER) | Medical Outcome Study (MOS) Sleep Questionnaires | Sleep Quantity Baseline | 5.86 Hours | Standard Error 1.65 |
| Gralise (Gabapentin ER) | Medical Outcome Study (MOS) Sleep Questionnaires | Sleep Quantity week 4 | 7.17 Hours | Standard Error 1.62 |
| Gralise (Gabapentin ER) | Medical Outcome Study (MOS) Sleep Questionnaires | Sleep quantity week 8 | 6.81 Hours | Standard Error 1.81 |
| Gralise (Gabapentin ER) | Medical Outcome Study (MOS) Sleep Questionnaires | Sleep quantity week 12 | 7.04 Hours | Standard Error 0.72 |
| Gralise (Gabapentin ER) | Medical Outcome Study (MOS) Sleep Questionnaires | Sleep quantity week 15 | 6.23 Hours | Standard Error 1.71 |
Secondary
Self Reported Side Effects.
Side / adverse effects were assessed at each follow up visits and resulted are as follows.
Time frame: 15 Weeks
Population: Subject who experienced pain, acute delirium, symptoms related to adhesions due to prior surgical procedures, extremity swelling, and possible drug interactions discontinued medications. Other reported side effects dissipated after subjects reached therapeutic dose of 1800mg of study medication taken at bedtime.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Dizzy | 3 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Extremity Swelling | 2 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Weight Gain | 2 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Drowsy | 8 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Irritability | 3 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Dry Eyes | 2 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Pain | 1 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Mood Changes | 2 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Difficulty Concentrating | 2 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Dry Mouth | 1 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Suspected Drug interaction | 1 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Acute Delerium | 1 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | Adhesion | 1 participants |
| Gralise (Gabapentin ER) | Self Reported Side Effects. | None | 12 participants |
Other Pre-specified
Patient Global Impression of Change (PGIC)
Patient Global impression of Change (PGIC) is an outcome commonly used measure of the efficacy of treatments. PGIC is a 7 point scale that requires the subjects to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.
Time frame: 15 Weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Gralise (Gabapentin ER) | Patient Global Impression of Change (PGIC) | PGIC After 12 weeks | 5.37 units on a scale | Standard Deviation 1.54 |
| Gralise (Gabapentin ER) | Patient Global Impression of Change (PGIC) | PGIC After 4 weeks | 4.96 units on a scale | Standard Deviation 1.61 |
| Gralise (Gabapentin ER) | Patient Global Impression of Change (PGIC) | PGIC After 8 weeks | 5.40 units on a scale | Standard Deviation 1.31 |
| Gralise (Gabapentin ER) | Patient Global Impression of Change (PGIC) | PGIC After 15 weeks | 4.44 units on a scale | Standard Deviation 1.97 |