Fibromyalgia
Conditions
Brief summary
The primary objective of this study is to assess the efficacy and safety of an extended-release (ER) formulation of pramipexole in comparison with placebo for the treatment of fibromyalgia. The objective of the open-label phase is to assess the safety profile and effect of Pramipexole (PPX) extended-release (ER) in fibromyalgia patients over a 24-week period.
Interventions
DRUGpramipexole ER
DRUGplacebo
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male and female outpatients greater than or equal to 18 years of age 2. Meet criteria for primary fibromyalgia as defined by the American College of Rheumatology (ACR): widespread aching pain in all four quadrants of the body and axial skeleton for greater than 3 months duration and greater than or equal to 11 of 18 tender points under digital palpitation examination with an approximate force of 4 kilograms per centimeters squared (kg/cm2) 3. Pain score of greater than or equal to 4 (scored once at screening and as a weekly mean at baseline) on the 11-point Likert pain scale with 0 = no pain and 10 = worst possible pain 4. Score of greater than or equal to 4 (= moderately ill) on the Clinical Global Impression of Severity (CGI-S) at screening and at baseline 5. All females of child-bearing potential must test negative for pregnancy at Visit 1. Females of child-bearing potential (not surgically sterilized and between menarche and two years postmenopausal) must agree to utilize medically acceptable and reliable means of birth control as determined by the investigator during the study and for one month following the last dose of study medication. Examples of reliable methods include: use of hormonal contraception (oral, injectable, or subcutaneous), double-barrier method, abstinence, partner with vasectomy, or hormonal intrauterine devices 6. Educational level and degree of understanding such that the patient can communicate intelligibly with the investigator and study coordinator 7. Judged to be reliable and agree to keep all appointments for clinic visits, tests, and procedures required by the protocol
Exclusion criteria
1. Employees of Boehringer Ingelheim (BI) (that is, employees, temporary contract workers, or designees responsible for the conduct of the study) 2. Have received treatment within 30 days prior to screening with a drug that has not received regulatory approval for any indication 3. Have previously completed or withdrawn from this study or any other study investigating pramipexole. 4. Any current or previous diagnosis of psychosis, bipolar disorder, or schizoaffective disorder as assessed by the Mini International Neuropsychiatric Interview (MINI) 5. Have any primary anxiety disorder within the past year as assessed by the Mini International Neuropsychiatric Interview (MINI) 6. Have any Diagnosis of Statistical Manual of Mental Diseases, 4th Edition (DSM-IV) Axis II disorder that would interfere with protocol compliance 7. Medium or high risk of suicidality as assessed by the Mini International Neuropsychiatric Interview (MINI) 8. History of substance abuse/dependence within the past year, excluding nicotine and caffeine 9. A positive urine drug screen for any substance of abuse or excluded medication 10. Women who are pregnant or breast-feeding 11. Have pain symptoms related to traumatic injury that will interfere with the interpretation of outcome measures 12. Patients with regional pain syndromes, multiple surgeries or failed back surgery syndrome 13. A confirmed or previous diagnosis of rheumatoid arthritis, inflammatory arthritis, or infectious arthritis, or an autoimmune disease 14. Abnormal C-Reactive Protein, Anti-Nuclear Antibody (ANA), Rheumatoid factor, or Thyroid Stimulating Hormone (TSH) 15. Any serious or unstable medical or psychiatric condition or clinically significant abnormalities in labs at screening that would lead to hospitalization during the course of the study or otherwise compromise study participation 16. Have uncontrolled seizures 17. Taking any prohibited medications that cannot be discontinued at screening 18. Patients who are treatment-refractory or whose response may be compromised by disability compensation issues 19. Patients with frequent or severe allergic reactions to multiple medications 20. Prior or current treatment with pramipexole 21. Clinically significant renal disease 22. Current or previous diagnosis of malignant melanoma 23. Clinically relevant ophthalmopathy 24. Documented sleep apnea
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in the Weekly Mean of the 24-hour Average Pain Score From a Daily Diary as Measured by the 11-point Likert Pain Scale | Baseline and Week 29 | The 11-point Likert Pain Scale is a numerical rating scale completed by the patient that measures the intensity of pain. The intensity scores range from 0 (no pain) to 10 (worst possible pain) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Short Form 36 (SF-36) Health Survey, Physical Functioning Subscale (Change From Baseline). | Baseline and Week 29 | The SF-36 Health Survey is a self-administered 36-item instrument completed by the patient . SF 36 has subscales as follows: i) physical functioning (PF), ii) role limitations due to physical problems (RP), iii) bodily pain (BP), iv) general health perceptions (GH), v) vitality (VT), vi) social function (SF), vii) role limitations due to emotional problems (RE), viii) mental health (MH),ix)physical component summary (PCS)and x)mental component summary(MCS). Among the subscales, Physical functioning was key secondary endpoint while other were additional secondary endpoints. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. The number of items per domain varies from 2 to 1 |
| The Proportion of Patients With at Least a 30% or at Least a 50% Improvement Relative to Baseline in Pain (Assessed on the 11-point Likert Pain Scale | Baseline and Week 29 | 11-Point Likert Pain Scale is a numerical rating scale completed by the patient that measures the intensity of pain. The intensity scores range from: 0 = no pain to 10 = worst possible pain . |
| Fibromyalgia Impact Questionnaire (FIQ) Total Score (Change From Baseline) | Baseline and Week 29 | FIQ is a self-reported scale completed by the patient that measures patient status, progress, and outcomes over the past week. The FIQ is composed of a total of 20 items; the first 11 items measure physical functioning, and each item is rated on a four-point Likert scale. Items 12 and 13 measure the number of days the patient felt well and the number of days the patient felt unable to work due to their fibromyalgia symptoms. Items 14 through 20 are numerical, 11-point Likert scales (marked in 10-point increments) on which the patient rates work difficulty, pain, fatigue, morning tiredness, stiffness, anxiety, and depression. The total score ranges from 0 to 80. A higher score indicates a more negative impact |
| Hospital Anxiety and Depression Scale (HADS) (Change From Baseline). | Baseline and Week 29 | The Hospital Anxiety and Depression Scale (HADS) measures the severity of anxiety and depression. The severity score ranges from: 0 = least severe to 3 = most severe. The total score ranges from 0 to 21; the higher the score, the more severe the anxious/depressive symptoms |
| The Short Form 36 (SF-36) Health Survey (Change From Baseline) (Excluding the Physical Functioning Subscale(PF)). | Baseline and Week 29 | The SF-36 Health Survey is a self-administered 36-item instrument completed by the patient . SF 36 has subscales as follows: i) physical functioning (PF), ii) role limitations due to physical problems (RP), iii) bodily pain (BP), iv) general health perceptions (GH), v) vitality (VT), vi) social function (SF), vii) role limitations due to emotional problems (RE), viii) mental health (MH),ix)physical component summary (PCS)and x)mental component summary(MCS). Among the subscales, Physical functioning was key secondary endpoint while other were additional secondary endpoints. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. The number of items per domain varies from 2 to 1 |
| The Proportion of Patients Very Much Improved or Much Improved on the Patient's Global Impression of Improvement (PGI-I) 7-point Scale | Week 29 (at the end of the maintenance phase) | PGI-I is a self-reported scale completed by the patient that measures the degree of improvement at the time of assessment. The score ranges from 1 = very much improved to 7 = very much worse |
| Multidimensional Assessment of Fatigue (MAF) Index (Change From Baseline) | Baseline and Week 29 | The Multidimensional Assessment of Fatigue (MAF) Index is a 16-item, self-reporting instrument designed to collect data on four dimensions of fatigue- severity, distress, degree of interference in activities of daily living, and timing . |
| Medical Outcomes Study (MOS) Sleep Scale (Change From Baseline) | Baseline and Week 29 | The Medical Outcomes Study (MOS) sleep scale is a 12-item (MOS1 to MOS12) self reporting sleep measure. |
| Clinical Global Impression of Severity (CGI-S Scores) | Baseline and Week 29 | Clinical Global Impression of Severity (CGI-S) Scale is a clinician's assessment of patient's severity of illness. The score ranges from 1 = normal, not at all ill to 7 = among the most extremely ill patients |
| Frequency of Rescue Medication for Pain | Week 29 | Acetaminophen/paracetamol (maximum of 4 g/day) to be allowed as rescue medication for pain. |
| Change From Baseline in Mean Tender Point Threshold | Baseline and Week 29 | The Tender Point Pain Threshold will be assessed for all 18 tender points by a study clinician. A dolorimeter will be used to exert the pressure at each point and to measure the threshold reading; when the patient first indicates pain, the threshold will be recorded in kg/sq.cm ;If the patient reports pain before 1.0 kg/sq.cm is reached (\>0 kg/sq.cm), 1.0 kg/sq.cm will be entered. If the patient does not report pain when the maximum pressure is applied (10.0 kg/sq.cm),0 (no pain) will be entered. |
| Euroqol- 5 Dimensions (EQ-5D) Survey (Change From Baseline) | Baseline and Week 29 | The Euroqol- 5 Dimension (EQ-5D) Health Survey is a generic, multidimensional, health related, quality-of-life instrument that contains two parts-a health status profile and a visual analog scale (VAS) to rate global health-related quality of life. The profile contains five items corresponding to five health domains- mobility, self-care, usual activities, pain/discomfort, and mood. A single score is generated for each health state. Data from the EQ-5D can be converted into 243 unique health states. For each health state, there exists a corresponding valuation that allows the patient's health to be represented as an index, which is a value between -0.594 and 1; the higher the score, the better the quality of life. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Patients receiving matching placebo | 31 |
| Pramipexole Patients receiving pramipexole | 30 |
| Total | 61 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 6 |
| Overall Study | Early termination of the trial | 22 | 24 |
| Overall Study | Lost to Follow-up | 2 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Placebo | Pramipexole | Total |
|---|---|---|---|
| Age, Continuous | 52.3 years STANDARD_DEVIATION 10.3 | 50.7 years STANDARD_DEVIATION 9.7 | 51.5 years STANDARD_DEVIATION 9.9 |
| Sex: Female, Male Female | 30 Participants | 30 Participants | 60 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 31 | 18 / 30 |
| serious Total, serious adverse events | 1 / 31 | 0 / 30 |
Outcome results
Primary
The Change in the Weekly Mean of the 24-hour Average Pain Score From a Daily Diary as Measured by the 11-point Likert Pain Scale
The 11-point Likert Pain Scale is a numerical rating scale completed by the patient that measures the intensity of pain. The intensity scores range from 0 (no pain) to 10 (worst possible pain)
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
Change From Baseline in Mean Tender Point Threshold
The Tender Point Pain Threshold will be assessed for all 18 tender points by a study clinician. A dolorimeter will be used to exert the pressure at each point and to measure the threshold reading; when the patient first indicates pain, the threshold will be recorded in kg/sq.cm ;If the patient reports pain before 1.0 kg/sq.cm is reached (\>0 kg/sq.cm), 1.0 kg/sq.cm will be entered. If the patient does not report pain when the maximum pressure is applied (10.0 kg/sq.cm),0 (no pain) will be entered.
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
Clinical Global Impression of Severity (CGI-S Scores)
Clinical Global Impression of Severity (CGI-S) Scale is a clinician's assessment of patient's severity of illness. The score ranges from 1 = normal, not at all ill to 7 = among the most extremely ill patients
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
Euroqol- 5 Dimensions (EQ-5D) Survey (Change From Baseline)
The Euroqol- 5 Dimension (EQ-5D) Health Survey is a generic, multidimensional, health related, quality-of-life instrument that contains two parts-a health status profile and a visual analog scale (VAS) to rate global health-related quality of life. The profile contains five items corresponding to five health domains- mobility, self-care, usual activities, pain/discomfort, and mood. A single score is generated for each health state. Data from the EQ-5D can be converted into 243 unique health states. For each health state, there exists a corresponding valuation that allows the patient's health to be represented as an index, which is a value between -0.594 and 1; the higher the score, the better the quality of life.
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
Fibromyalgia Impact Questionnaire (FIQ) Total Score (Change From Baseline)
FIQ is a self-reported scale completed by the patient that measures patient status, progress, and outcomes over the past week. The FIQ is composed of a total of 20 items; the first 11 items measure physical functioning, and each item is rated on a four-point Likert scale. Items 12 and 13 measure the number of days the patient felt well and the number of days the patient felt unable to work due to their fibromyalgia symptoms. Items 14 through 20 are numerical, 11-point Likert scales (marked in 10-point increments) on which the patient rates work difficulty, pain, fatigue, morning tiredness, stiffness, anxiety, and depression. The total score ranges from 0 to 80. A higher score indicates a more negative impact
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
Frequency of Rescue Medication for Pain
Acetaminophen/paracetamol (maximum of 4 g/day) to be allowed as rescue medication for pain.
Time frame: Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
Hospital Anxiety and Depression Scale (HADS) (Change From Baseline).
The Hospital Anxiety and Depression Scale (HADS) measures the severity of anxiety and depression. The severity score ranges from: 0 = least severe to 3 = most severe. The total score ranges from 0 to 21; the higher the score, the more severe the anxious/depressive symptoms
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
Medical Outcomes Study (MOS) Sleep Scale (Change From Baseline)
The Medical Outcomes Study (MOS) sleep scale is a 12-item (MOS1 to MOS12) self reporting sleep measure.
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
Multidimensional Assessment of Fatigue (MAF) Index (Change From Baseline)
The Multidimensional Assessment of Fatigue (MAF) Index is a 16-item, self-reporting instrument designed to collect data on four dimensions of fatigue- severity, distress, degree of interference in activities of daily living, and timing .
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
The Proportion of Patients Very Much Improved or Much Improved on the Patient's Global Impression of Improvement (PGI-I) 7-point Scale
PGI-I is a self-reported scale completed by the patient that measures the degree of improvement at the time of assessment. The score ranges from 1 = very much improved to 7 = very much worse
Time frame: Week 29 (at the end of the maintenance phase)
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
The Proportion of Patients With at Least a 30% or at Least a 50% Improvement Relative to Baseline in Pain (Assessed on the 11-point Likert Pain Scale
11-Point Likert Pain Scale is a numerical rating scale completed by the patient that measures the intensity of pain. The intensity scores range from: 0 = no pain to 10 = worst possible pain .
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
The Short Form 36 (SF-36) Health Survey (Change From Baseline) (Excluding the Physical Functioning Subscale(PF)).
The SF-36 Health Survey is a self-administered 36-item instrument completed by the patient . SF 36 has subscales as follows: i) physical functioning (PF), ii) role limitations due to physical problems (RP), iii) bodily pain (BP), iv) general health perceptions (GH), v) vitality (VT), vi) social function (SF), vii) role limitations due to emotional problems (RE), viii) mental health (MH),ix)physical component summary (PCS)and x)mental component summary(MCS). Among the subscales, Physical functioning was key secondary endpoint while other were additional secondary endpoints. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. The number of items per domain varies from 2 to 1
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))
Secondary
The Short Form 36 (SF-36) Health Survey, Physical Functioning Subscale (Change From Baseline).
The SF-36 Health Survey is a self-administered 36-item instrument completed by the patient . SF 36 has subscales as follows: i) physical functioning (PF), ii) role limitations due to physical problems (RP), iii) bodily pain (BP), iv) general health perceptions (GH), v) vitality (VT), vi) social function (SF), vii) role limitations due to emotional problems (RE), viii) mental health (MH),ix)physical component summary (PCS)and x)mental component summary(MCS). Among the subscales, Physical functioning was key secondary endpoint while other were additional secondary endpoints. Each domain is scored by summing the individual items and transforming the scores into a 0 to 100 scale, with higher scores indicating better health status or functioning. The number of items per domain varies from 2 to 1
Time frame: Baseline and Week 29
Population: FAS (All randomized and treated patients with a baseline and at least one post-baseline will be included in the Full Analysis Set (FAS))