Clinical trial NCT00154063: Efficacy and Safety Study of E2007 in Migraine Prophylaxis
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Evaluate the Efficacy and Safety of E2007 in Migraine Prophylaxis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Migraine Prophylaxis
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2005-09-12
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Change From Baseline in Migraine Period Frequency Per 28 Days in Treatment Phase (LOCF)
timeFrame: Baseline to Week 19
Secondary outcomes:
measure: Change From Baseline in Average Duration Per Migraine Attack in Treatment Phase (LOCF)
timeFrame: Baseline to Week 19
measure: Change From Baseline in Average Migraine Severity Per Migraine Attack in Treatment Phase (LOCF)
timeFrame: Baseline to Week 19
measure: Change From Baseline in Migraine Attack Frequency Per 28 Days in Treatment Phase (LOCF)
timeFrame: Baseline to Week 19
measure: Change From Baseline in Migraine Period Frequency Per 28 Days in Maintenance Phase
timeFrame: Baseline, Week 11 to Week 19
measure: Change From Baseline in Number of Days Requiring Symptomatic Rescue Medication Per 28 Days in Treatment Phase (LOCF)
timeFrame: Baseline to Week 19
measure: Change From Baseline in Number of Days With Migraine Attack Per 28 Days in Treatment Phase (LOCF)
timeFrame: Baseline to Week 19
measure: Change From Baseline in Number of Participants With Patient Global Impression of Change (PGIC) of Migraine (LOCF)
timeFrame: Baseline to Week 23
measure: Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Headache Pain Score
timeFrame: Baseline, Week 23
measure: Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Headaches
timeFrame: Baseline, Week 23
measure: Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Less Housework
timeFrame: Baseline, Week 23
measure: Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Less Work or School
timeFrame: Baseline, Week 23
measure: Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Missed Housework
timeFrame: Baseline, Week 23
measure: Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Missed Non-Work Activities
timeFrame: Baseline, Week 23
measure: Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Missed Work or School
timeFrame: Baseline, Week 23
measure: Percentage of Participants With a Greater Than or Equal to 50% Decrease in Migraine Attack Frequency Per 28 Days in Treatment Phase (LOCF)
timeFrame: Week 5 to Week 19
measure: Percentage of Participants With a Greater Than or Equal to 50% Decrease in Migraine Period Frequency Per 28 Days in Treatment Phase (LOCF)
timeFrame: Week 5 to Week 19
Other outcomes:
Locations:
city: Oceanside
country: United States
facility: Investigational Site
state: California
city: Santa Monica
country: United States
facility: Investigational Site
state: California
city: Tampa
country: United States
facility: Investigational Site
state: Florida
city: West Palm Beach
country: United States
facility: Investigational Site
state: Florida
city: Chicago
country: United States
facility: Investigational Site
state: Illinois
city: Springfield
country: United States
facility: Investigational Site
state: Missouri
city: Mount Vernon
country: United States
facility: Elkind Headache Center
state: New York
city: Greensboro
country: United States
facility: Investigational Site
state: North Carolina
city: Houston
country: United States
facility: Investigational Site
state: Texas
Study officials:
affiliation: Eisai Inc.
name: Julia Young, M.D., Ph.D.
role: STUDY_DIRECTOR
References: