Efficacy and Safety of Eslicarbazepine Acetate as Therapy in Subjects With Fibromyalgia
Condition: Fibromyalgia
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes
Intervention: Placebo; ESL 400 mg; ESL 800 mg; ESL 1200 mg
Intervention description: Tablets; tablets; tablets; tablets
Intervention MeSH terms: Eslicarbazepine acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 528.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: fibromyalgia; Eslicarbazepine acetate (BIA 2-093); ESL

Summary:

      This was a double-blind, randomised, placebo-controlled, parallel-group, multicentre,
      multinational, Phase II study in 528 subjects with pain due to Fibromyalgia syndrome(FMS).
      Subjects were randomised in a 1:1:1:1 ratio to receive placebo, Eslicarbazepine acetate (ESL)
      400 mg once daily (QD), ESL 800 mg QD or ESL 1200 mg QD. The study was carried out as
      follows.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject was male or female, 18 years of age or older (according to Amendment #1 for
             Czech Republic [24 MARCH 2009]: 18 to 65 years of age).

          -  Subject was able and willing to provide written informed consent to participate in the
             study after having the opportunity to review the Subject Information Sheet and
             Informed Consent Form.

          -  Subject met the American College of Rheumatology (ACR) 1990 diagnostic criteria for
             FMS (widespread pain for at least 3 months and pain in at least 11 of 18 tender
             points) (according to Amendment #1 for Czech Republic [24 MARCH 2009]: and the
             subject's current FMS treatment was either inefficacious or had intolerable side
             effects).

          -  Subject was willing and able to understand and comply with all study requirements, in
             the judgment of the investigator.

          -  Subject had negative results on the urine test for drugs of abuse at V1 (Screening
             Visit), except for medications/drugs reported by the subject at the Screening Visit.

          -  Subject use of allowable non-pharmacological therapies was stable for at least 4 weeks
             prior to V1 (Screening Visit) and would be maintained at the stable regimen throughout
             the study.

          -  Female subject was surgically sterile (i.e. bilateral tubal ligation, bilateral
             oophorectomy or hysterectomy) or at least 2 years post-menopausal or, if of
             childbearing potential, she was sexually abstinent or agreed to use a medically
             acceptable non-hormonal method of contraception

          -  Addendum according to Amendment #1 for Czech Republic [24 MARCH 2009]: Hormonal
             contraceptives were not acceptable as a contraceptive method in this study. However,
             their intake was not forbidden throughout the study.

          -  Addendum according to Amendment #1 for Spain [19 JANUARY 2009] and for United Kingdom
             [24 MARCH 2009]: Male subject was sexually abstinent or agreed to use reliable
             contraceptive methods (i.e. double-barrier method: 1 male barrier [male condom] plus 1
             female barrier method [female condom, spermicide or intrauterine device]. This was
             mandatory even for sexually active men who had been sterilised.

          -  Subject had a negative urine test for drugs of abuse.

          -  The subject had completed at least 4 subject diary pain assessments satisfactorily
             within the past 7 days prior to V2 and the average pain score was ≥4 and ≤9.

        Exclusion Criteria:

          -  Subject had a known hypersensitivity to ESL or to other carboxamide derivatives (e.g.
             oxcarbazepine, carbamazepine) or to any of the excipients.

          -  Subject had a history of or current active malignancy except for the following: basal
             cell carcinoma which had been treated; and malignancies that were successfully treated
             and had no recurrence within 5 years before V1 (Screening Visit).

          -  Subject had a severe hepatic, renal, respiratory, hematologic or immunologic illness,
             unstable cardiovascular disease or any other medical or psychiatric condition that, in
             the judgment of the investigator, made the subject inappropriate for entry into this
             study.

          -  Subject had a second or third-degree atrioventricular blockade not corrected with a
             pacemaker or any other clinically significant abnormality in the 12-lead ECG as
             determined by the investigator.

          -  Subject had a history of illicit drug or alcohol abuse within 2 years before V1
             (Screening Visit).

          -  Subject had received an investigational drug (or a medical device) within 3 months of
             Screening or was currently participating in another study of an investigational drug
             (or a medical device).

          -  Subject was pregnant or nursing.

          -  Subject was an employee of the investigator or study centre, with direct involvement
             in the proposed study or other studies under the direction of that investigator or
             study centre or was a family member of the employees or the investigator.

          -  Subject had any of the following: an inflammatory muscle or rheumatologic disease
             other than FMS; multiple sclerosis; active infections; untreated endocrine disorders;
             uncontrolled hypo- or hyper-thyroidism of any type.

          -  Subjects whose pain was not due primarily to FMS.

          -  Subject underwent tender point injection within 30 days before V1 (Screening Visit)
             and/or subject was unwilling to refrain from tender point injection throughout the
             study.

          -  Subject had a white blood cell (WBC) count <2.5 × 109/L, neutrophil count <1.5 ×
             109/L, Na+ <125 mmol/L or alanine aminotransferase (ALT) or aspartate aminotransferase
             (AST) ≥2 × the upper limit of normal at V1 (Screening Visit) or any other clinically
             relevant laboratory abnormality that, in the investigator's opinion, could compromise
             the subject's safety.

          -  Subject had abnormal values for antinuclear antibody (ANA >1/160) or rheumatoid factor
             (RF >15 IU/mL) at V1 (Screening Visit). After approval of the global amendment in
             respective countries, the limit for ANA was changed to ≥1/160.

          -  Subject had abnormal Westergren erythrocyte sedimentation rate (ESR) at V1 (Screening
             Visit) (ESR >40 mm/h).

          -  Subject had creatinine clearance (CLCr) lower than 60 mL/min at Screening.

          -  Subject had a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≥35 or a
             score of 4 to 6 on question 10 of the MADRS at V1 (Screening Visit).

          -  Subject used prohibited concomitant medications during the 2-week Baseline Period or
             used fluoxetine during the 30 days before V1 (Screening Visit).

          -  Subject used opiates every day for the 30 days before V1 (Screening Visit) for the
             control of pain related to FMS.

          -  Exclusion criterion at V2:

          -  Subject had a MADRS total score ≥35 or a score of 4 to 6 on question 10 of the MADRS.