Efficacy and Safety of Eslicarbazepine Acetate as Preventive Therapy for Subjects With Migraine
Condition: Migraine
MeSH terms: Migraine Disorders
Intervention: Placebo; ESL 1200 mg; ESL 800 mg
Intervention description: Tablets; Eslicarbazepine acetate was supplied in 400-mg and 600-mg tablets and was administered with a dose of 800 or 1200 mg QD in the evening by the oral route.; Eslicarbazepine acetate was supplied in 400-mg and 600-mg tablets and was administered with a dose of 800 or 1200 mg QD in the evening by the oral route.
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: 452.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: migraine; ESL; eslicarbazepine acetate

Summary:

      This was a multinational, randomised, double-blind, placebo-controlled, parallel-group study
      to evaluate the efficacy, safety, and tolerability of multiple doses of ESL as prophylactic
      treatment in subjects with migraine with or without aura. Subjects were randomised in a 1:1:1
      ratio to receive placebo, ESL 800 mg/day once daily (QD), or ESL 1200 mg/day QD.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Women or men, 18 years of age or older (according to Amendment #1 for Czech Republic
             [24 Mar 2009]: 18 to 65 years of age).

          -  Diagnosis (established prior to 50 years of age) of migraine headaches for at least 1
             year, and a well-documented history of migraine headaches with or without aura
             according to the criteria of the IHS (see Section 3.5.6.1) for at least 3 months
             (according to Amendment #1 for Czech Republic [24 Mar 2009]: for at least 3 months
             with at least 3 migraine attacks per month in each of these 3 months).

          -  At least 2 (according to Amendment #1 for Czech Republic [24 Mar 2009]: at least 3)
             (and no more than 10) well-defined migraine headache attacks per month, with at least
             24 h of freedom from headaches and other symptoms of migraine between attacks.

          -  Able to distinguish the migraine headache attacks from other types of common headaches
             (tension-type headaches, sinus-related headaches, etc.).

          -  Not taking any prophylactic migraine therapies for at least 2 weeks prior to Baseline
             Visit (V2). Flunarizine had to be discontinued at least 4 weeks prior to V2.

          -  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 (ICF).

          -  Able and willing to comply with all study requirements, in the judgment of the
             investigator.

          -  Women were surgically sterile (i.e. bilateral tubal ligation, bilateral oophorectomy,
             or hysterectomy), or at least 2 years postmenopausal or, if of childbearing potential,
             were sexually abstinent or agreed to use medically acceptable non-hormonal methods of
             contraception (see Section 3.3.3). (According to Amendment #1 for Czech Republic [24
             Mar 2009]: Women were sexually abstinent or agreed to use a double-barrier method of
             contraception. Hormonal contraceptives were not acceptable as a contraceptive method
             in this study. However, their intake was not forbidden throughout the study.)

        Exclusion Criteria:

          -  A known hypersensitivity to ESL or to other carboxamide derivatives (e.g.
             oxcarbazepine, carbamazepine), or to any of the excipients.

          -  Suspected or confirmed medication-overuse headache.

          -  More than 14 headache days (migraine or other headache types) per month in either of
             the 2 months prior to screening.

          -  Consistent or recurrent frequent headaches (i.e. ≥6 headache days a month) other than
             migraine headaches.

          -  Unable to discontinue medications primarily used for migraine prophylaxis that have
             been commonly used for other indications (tricyclic agents, divalproic acid,
             topiramate, etc.). A subject who received beta blockers or calcium channel blocker
             therapy for reasons other than migraine prophylaxis was eligible for inclusion,
             provided his/her dosing regimen had been stable for ≥2 months and was not expected to
             change during the course of the study.

          -  Using prohibited concomitant medication (see Section 3.5.5.2).

          -  A white blood cell (WBC) count <2.5 * 109/L, neutrophil count <1.5 * 109/L, sodium
             <125 mmol/L, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2
             times 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.

          -  A creatinine clearance lower than 60 mL/min at screening.

          -  A second- or third-degree atrioventricular blockade not corrected with a pacemaker or
             any other clinically significant abnormality in the 12-lead electrocardiogram (ECG) as
             determined by the investigator.

          -  Pregnant or nursing women.

          -  A history of chronic alcohol or drug abuse or addiction within the last 2 years.

          -  A severe hepatic, renal, respiratory, haematological, 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.

          -  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 medical
             device).

          -  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.