Pramipexole ER vs. Placebo in Fibromyalgia

Fibromyalgia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00689052
• Other study ID #: 248.637
• Status: Terminated
• Phase: Phase 2
• First received: May 29, 2008
• Last updated: June 3, 2014
• Start date: July 2008

Study information

• Verified date: May 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 61
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibromyalgia
• Myofascial Pain Syndromes

Intervention

Drug:
• pramipexole ER

• placebo

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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)	Baseline and Week 29	No
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	Week 29 (at the end of the maintenance phase)	No
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	Baseline and Week 29	No
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 .	Baseline and Week 29	No
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	Baseline and Week 29	No
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	Baseline and Week 29	No
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	Baseline and Week 29	No
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.	Baseline and Week 29	No
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 .	Baseline and Week 29	No
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.	Baseline and Week 29	No
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	Baseline and Week 29	No
Secondary	Frequency of Rescue Medication for Pain	Acetaminophen/paracetamol (maximum of 4 g/day) to be allowed as rescue medication for pain.	Week 29	No
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.	Baseline and Week 29	No

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