Efficacy and Safety Study of E2007 in Migraine Prophylaxis
Condition: Migraine Prophylaxis
MeSH terms: Migraine Disorders
Intervention: E2007; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 206.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No

Summary:

      This was a 22-week, prospective, randomized, double-blind, placebo-controlled, multicenter,
      parallel-group study that included a 4-week Baseline Phase at the beginning and a 4-week
      single-blind placebo Safety Phase at the end of the study.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients of any race, 18 to 65 years of age inclusive.

          2. Patients with a history of migraine (with or without aura) according to the Headache
             Classification Committee of the IHS. Migraine attacks have to have had an onset before
             age 50 and have to have been present for at least 12 months.

          3. Patients with 4-12 qualified migraine attacks per month over the past three months
             prior to Screening, as well as during the four weeks of the Baseline Phase will be
             eligible for entry into this study. The interval between two qualified migraine
             attacks should be at least 24 hours to be counted as distinct migraine attacks. A
             qualified migraine attack without aura is defined as a headache that lasts 4-72 hours
             (if untreated or unsuccessfully treated) or if successfully treated (revised per
             Amendment 01). This attack has at least two of the following characteristics:
             unilateral location, pulsating quality, moderate or severe intensity that inhibits or
             prohibits daily activities or aggravation by routine physical activities such as
             walking up stairs. In addition, at least one of the following symptoms must be present
             during the headache: nausea, vomiting, or photophobia and phonophobia (revised per
             Amendments 01 and 02). A qualified migraine attack with aura must fulfill the same
             criteria as the headache attack, plus have an associated aura as defined by the
             Migraine Criteria of the Headache Classification Committee of the International
             Headache Society. An aura alone that requires acute migraine treatment will also be
             considered a migraine attack.

          4. Male and female patients will be eligible for enrollment. Females should be either of
             non-childbearing potential by reason of surgery, radiation, menopause (one year post
             onset), or of childbearing potential and practicing a medically acceptable method of
             contraception (eg, abstinence, a barrier method plus spermicide, or IUD) for at least
             one month before study randomization and for two months after the end of the study,
             and have a negative serum B-hCG at Screening. Pregnant and/or lactating females are
             excluded. Those women using hormonal contraceptives must also be using an additional
             approved method of contraception (eg, a barrier method plus spermicide, or IUD)
             starting with the Baseline Phase and continuing throughout the entire study period.

          5. Patients with a Body Mass Index (BMI) between 19 to 40 kg/m2 inclusive at Screening.

          6. Patients who are willing to participate and have provided written informed consent
             prior to being exposed to any study-related procedures.

        Exclusion Criteria:

          1. Patients with chronic daily headaches as defined by more than 14 headache days per
             month on average during the three months prior to Screening,

          2. Patients with cluster headaches and other trigeminal autonomic cephalalgias, and other
             primary headaches (except tension-type headache) and secondary headaches (defined
             according to the Headache Classification Committee of the IHS 2004),

          3. Patients with a history of being non-responsive to more than two classes of adequately
             conducted, prophylactic migraine treatments (e.g., beta blockers, calcium channel
             blockers, tricyclics, MAOIs, valproate (divalproex), topiramate, gabapentin),

          4. Patients who use the following medications as described:

               -  Use of marketed triptans for 10 days or greater per month on average,

               -  Use of ergot-containing medications for ten days or greater per month on average,

               -  Use of NSAIDs, acetaminophen, or isometheptene-containing agents for 15 days or
                  greater per month on average,

               -  Use of opioids for 10 days or greater per month on average,

               -  Use of any two or more of the above medications for 15 days or greater per month
                  on average,

          5. Patients with clinically significant neurological illness, other than migraine, that,
             in the opinion of the Investigators, may have the potential of altering pain
             perception or reporting,

          6. Patients with a history of or currently having major psychiatric disorders including
             schizophrenia, major depressive disorder, or bipolar disorder,

          7. Patients who are known to be positive for hepatitis B surface antigen, hepatitis B
             core antibody, hepatitis C antibody, or human immunodeficiency virus (HIV),

          8. Patients with elevations of liver enzymes, alanine aminotransferase (ALT), and
             aspartate aminotransferase (AST) >= 1.5 times the upper limit of normal (ULN),

          9. Patients with evidence of significant active hematological disease; white blood cell
             count cannot be less than or equal to 2500/uL or an absolute neutrophil count less
             than or equal to 1000/uL,

         10. Patients with clinically significant ECG abnormality, including prolonged QTc
             (Fridericia correction) defined as >= 450 msec for males and >= 470 msec for females,

         11. Patients with clinically significant active hepatic disease, cardiovascular,
             metabolic, respiratory, renal, endocrinological, gastrointestinal diseases, and
             bacterial or viral infections within 30 days prior to Screening or during the Baseline
             Phase,

         12. Patients with known or suspected history of alcoholism or drug abuse within the
             previous two years, or a positive finding on urinary drug screening of other than
             prescribed medications,

         13. Patients who have had severe allergic reactions to multiple drugs,

         14. Patients with any other condition that would make them, in the opinion of the PI,
             unsuitable for this study,

         15. Patients that have participated in a study involving administration of an
             investigational compound (including E2007) within one month of Visit 1 (Screening),

         16. Patients with a known or suspected allergy to lactose, excluding lactose intolerance,

         17. Patients who use the following medications for any medical reason during the study:
             beta-blockers, tricyclic antidepressants, antiepileptics, calcium channel blockers,
             monoamine oxidase inhibitors, NSAIDs daily, magnesium supplements at high doses (ie,
             600 mg/day), riboflavin at high doses (ie, 100 mg/day), corticosteroids, local
             anesthetics, botuliunum toxin, or herbal preparations such as feverfew or St. John's
             Wort. Patients who use non-pharmacological prophylactic approaches that were started
             at least one month prior to Screening may be continued throughout the study.

         18. (revised per Amendment 03)

         19. Patients who fail to complete the migraine diary adequately during the Baseline Phase
             (ie, patients, who do not have complete diary entries for at least 21 days of the
             Baseline Phase).

        Randomized patients will be both male and female, 18-65 years of age, of any race, with a
        history of migraine headaches (with or without aura according to the Headache
        Classification Committee of the International Headache Society (IHS, 2004 guideline) for at
        least 12 months, with an onset before age 50, experiencing 4-12 migraine attacks per month
        during both the 3 months prior to Screening and the Baseline Phase. Patients' Body Mass
        Index (BMI) should be between 19 to 40 kg/m2 inclusive at Screening.