Pramipexole ER vs. Placebo in Fibromyalgia

A Randomized, Double-blind, Placebo-controlled, Dose Titration Efficacy and Safety Study of Pramipexole ER (0.75 to 4.5 mg) Administered Orally Once Daily Versus Placebo Over a 16-week Maintenance Phase in Patients Diagnosed With Fibromyalgia, as Assessed by the American College of Rheumatology (ACR) Criteria Followed by a 24-week Open-label Extension Phase

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.

Study Overview

• Status: Terminated
• Conditions: Fibromyalgia
• Intervention / Treatment: Drug: placebo; Drug: pramipexole ER

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States
      • 248.637.01009 Boehringer Ingelheim Investigational Site
  • Arizona
    • Phoenix, Arizona, United States
      • 248.637.01033 Boehringer Ingelheim Investigational Site
    • Tucson, Arizona, United States
      • 248.637.01045 Boehringer Ingelheim Investigational Site
  • Arkansas
    • Hot Springs, Arkansas, United States
      • 248.637.01034 Boehringer Ingelheim Investigational Site
  • California
    • Arcadia, California, United States
      • 248.637.01032 Boehringer Ingelheim Investigational Site
    • Los Angeles, California, United States
      • 248.637.01044 Boehringer Ingelheim Investigational Site
    • Santa Ana, California, United States
      • 248.637.01036 Boehringer Ingelheim Investigational Site
  • Colorado
    • Englewood, Colorado, United States
      • 248.637.01042 Boehringer Ingelheim Investigational Site
  • Connecticut
    • Danbury, Connecticut, United States
      • 248.637.01031 Boehringer Ingelheim Investigational Site
  • Florida
    • Deland, Florida, United States
      • 248.637.01035 Boehringer Ingelheim Investigational Site
    • Ft. Myers, Florida, United States
      • 248.637.01023 Boehringer Ingelheim Investigational Site
    • Orlando, Florida, United States
      • 248.637.01047 Boehringer Ingelheim Investigational Site
    • Palm Beach Gardens, Florida, United States
      • 248.637.01043 Boehringer Ingelheim Investigational Site
    • Sunrise, Florida, United States
      • 248.637.01040 Boehringer Ingelheim Investigational Site
    • Tampa, Florida, United States
      • 248.637.01027 Boehringer Ingelheim Investigational Site
  • Georgia
    • Atlanta, Georgia, United States
      • 248.637.01007 Boehringer Ingelheim Investigational Site
  • Illinois
    • Chicago, Illinois, United States
      • 248.637.01028 Boehringer Ingelheim Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States
      • 248.637.01010 Boehringer Ingelheim Investigational Site
  • Massachusetts
    • Newton, Massachusetts, United States
      • 248.637.01016 Boehringer Ingelheim Investigational Site
  • Michigan
    • Lansing, Michigan, United States
      • 248.637.01014 Boehringer Ingelheim Investigational Site
  • Mississippi
    • Flowood, Mississippi, United States
      • 248.637.01020 Boehringer Ingelheim Investigational Site
    • Picayune, Mississippi, United States
      • 248.637.01018 Boehringer Ingelheim Investigational Site
  • Missouri
    • Kansas City, Missouri, United States
      • 248.637.01012 Boehringer Ingelheim Investigational Site
  • Montana
    • Billings, Montana, United States
      • 248.637.01017 Boehringer Ingelheim Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States
      • 248.637.01024 Boehringer Ingelheim Investigational Site
  • New York
    • Albany, New York, United States
      • 248.637.01008 Boehringer Ingelheim Investigational Site
    • New York, New York, United States
      • 248.637.01002 Boehringer Ingelheim Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • 248.637.01025 Boehringer Ingelheim Investigational Site
  • North Dakota
    • Fargo, North Dakota, United States
      • 248.637.01026 Boehringer Ingelheim Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States
      • 248.637.01004 Boehringer Ingelheim Investigational Site
    • Columbus, Ohio, United States
      • 248.637.01038 Boehringer Ingelheim Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • 248.637.01003 Boehringer Ingelheim Investigational Site
  • Oregon
    • Medford, Oregon, United States
      • 248.637.01046 Boehringer Ingelheim Investigational Site
    • Portland, Oregon, United States
      • 248.637.01006 Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Duncansville, Pennsylvania, United States
      • 248.637.01039 Boehringer Ingelheim Investigational Site
  • Rhode Island
    • Warwick, Rhode Island, United States
      • 248.637.01015 Boehringer Ingelheim Investigational Site
  • Texas
    • Austin, Texas, United States
      • 248.637.01019 Boehringer Ingelheim Investigational Site
    • San Antonio, Texas, United States
      • 248.637.01037 Boehringer Ingelheim Investigational Site
  • Utah
    • Salt Lake City, Utah, United States
      • 248.637.01041 Boehringer Ingelheim Investigational Site
  • Washington
    • Renton, Washington, United States
      • 248.637.01021 Boehringer Ingelheim Investigational Site
    • Seattle, Washington, United States
      • 248.637.01029 Boehringer Ingelheim Investigational Site
    • Spokane, Washington, United States
      • 248.637.01011 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pramipexole ER; 0.75 mg to 4.5 mg tablets of Pramipexole ER, once daily in the evening	Drug: pramipexole ER
Placebo Comparator: Placebo; Placebo tablets, once daily in the evening	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Baseline and Week 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Week 29 (at the end of the maintenance phase)
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	Baseline and Week 29
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 .	Baseline and Week 29
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	Baseline and Week 29
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	Baseline and Week 29
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	Baseline and Week 29
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.	Baseline and Week 29
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 .	Baseline and Week 29
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.	Baseline and Week 29
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	Baseline and Week 29
Frequency of Rescue Medication for Pain	Acetaminophen/paracetamol (maximum of 4 g/day) to be allowed as rescue medication for pain.	Week 29
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.	Baseline and Week 29

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: May 29, 2008
• First Submitted That Met QC Criteria: June 2, 2008
• First Posted (Estimate): June 3, 2008

Study Record Updates

• Last Update Posted (Estimate): June 9, 2014
• Last Update Submitted That Met QC Criteria: June 3, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: 248.637