Official Title: “A Randomized, Pilot Clinical Trial to Assess the Comparative Efficacy and Tolerability of Quetiapine XR Versus Amitriptyline for the Treatment of Patients With Fibromyalgia”

Quetiapine, a second generation antipsychotic, has shown beneficial activity on fibromyalgia symptomatology, administered as add-on treatment, in a sample of 35 patients. The purpose of the present study is to compare, in a controlled setting, the efficacy and the tolerability of quetiapine extended release with amitriptyline in the treatment of patients with fibromyalgia

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2009

Intervention(s) in this Clinical Trial

• Drug: amitriptyline
  • initial dose 10 mg/day, target dose: 25 mg/day, maximum dose: 75 mg/day, dosage form: tablets, duration: 16 weeks
• Drug: quetiapine
  • initial dose: 50 mg/day, target dose: 100 mg/day, maximum dose: 300 mg/day, dosage form:extended release tablets , duration: 16 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: amitriptyline
• Experimental: quetiapine

Primary Measures

• Mean change from baseline to endpoint in the total score of Fibromyalgia Impact Questionnaire
  • Time Frame: baseline, 4, 8, 12 and 16 weeks
    Safety Issue?: No

Secondary Measures

• Change from baseline to endpoint in the scores of the Brief Pain Inventory, the Pittsburgh Sleep Quality Inventory, the Beck Depression Inventory, and the State and Trait Anxiety Inventory
  • Time Frame: baseline, 4, 8, 12 and 16 weeks
    Safety Issue?: No
• Discontinuation rates due to treatment-related adverse events, proportion of patients experiencing adverse events, proportion of patients experiencing serious adverse events, adverse events description and classification.
  • Time Frame: baseline, 0, 4, 8, 12 and 16 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• 1. Male or female patients aged 18 70 years.
• 2. Meeting American College of Rheumatology criteria for primary fibromyalgia: widespread aching pain in all four quadrants of the body and axial skeleton and greater than or equal to 11 of 18 tender points under digital palpation examination.
• 3. A FIQ total score (0 100) of 40 or greater
• 4. A score of 4 or greater on the average pain item of the BPI
• 5. Written informed consent
• 6. Female patients of childbearing potential must be using a reliable contraceptive method and have a negative urine human chorionic gonadotropin (HCG) test at enrolment.
• 7. Able to understand and comply with the requirements of the study.

Exclusion Criteria:

• 1. Evidence of current traumatic injury, inflammatory rheumatic disease, or infectious or endocrine related joint disease.
• 2. A lifetime history of hypomania, mania, psychosis or dementia.
• 3. Current primary Axis I diagnosis other than major depressive disorder
• 4. Substance or alcohol dependence at enrolment and within the past 12 months (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM IV
• 5. Severe depression as evidenced by a Beck Depression Inventory score ≥ 30
• 6. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
• 7. History of seizures
• 8. Known lack of response to 2, or more than 2, different type of antidepressants in depression of fibromyalgia.
• 9. Pregnancy or breast feeding.
• 10. Patients with a history of urinary retention, angle closure glaucoma, or increased intraocular pressure.
• 11. Patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), cerebrovascular disease or conditions which would predispose patients to severe hypotension (dehydration, hypovolemia and treatment with antihypertensive medications).
• 12. Patients who have received IMAOs, SSRIs or other antidepressants within two weeks of randomization.
• 13. Current or past history of kidney or liver insufficiency
• 14. Prior to randomization. Unwillingness to discontinue previously prescribed drugs for fibromyalgia other than those authorized in the protocol, as acetaminophen and bromazepam
• 15. Patients who have received quetiapine or amitriptyline within 1 year of randomization.
• 16. Patients with known intolerance or lack of response to quetiapine fumarate and/or amitriptyline, as judged by the investigator
• 17. Use of any of the following cytochrome P450 3A4 inhibitors within 14 days of enrolment, including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine, and saquinavir
• 18. Use of any of the following cytochrome P450 inducers within 14 days of enrolment, including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St.
• John's wort, and glucocorticoids
• 19. Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM IV criteria within 4 weeks of enrolment
• 20. Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment, with clinical relevance.
• 21. Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension), as judged by the investigator
• 22. Involvement in planning and conduct of the study
• 23. Previous enrolments or randomisation of treatment in the present study.
• 24. Participation in another trial with drugs within 4 weeks of enrolment into this study or a longer period in accordance with local requirements.
• 25. Patients with uncontrolled Diabetes Mellitus (DM)
• 26. An absolute neutrophil count (ANC) equal or lower than 1.5 x 109 per liter.
• 27. Patients who show at the randomization visit a reduction in the FIQ total score equal or greater than 20% from the screening visit.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Universidad de Granada

Overall Clinical Trial Officials and Contacts

Elena P Calandre, MD Principal Investigator Clinical Pharmacology Department of the Hospital Clinico Universitario San Cecilio  

Overall Contact: Elena P. Calandre, MD +34 958023135 epita@ugr.es

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00766350

Study ID Number: D1443C00024

ClinicalTrials.gov Identifier: NCT00766350

Health Authority: Spain: Spanish Agency of Medicines