Efficacy and Safety Study of E2007 in Migraine Prophylaxis

Migraine Prophylaxis Clinical Trial

Official title:

A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group Study to Evaluate the Efficacy and Safety of E2007 in Migraine Prophylaxis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00154063
• Other study ID #: E2007-A001-210
• Status: Completed
• Phase: Phase 2
• First received: September 6, 2005
• Last updated: May 21, 2015
• Start date: January 2005
• Est. completion date: June 2006

Study information

• Verified date: August 2009
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Other known NCT identifiers

• NCT00239941

Recruitment information / eligibility

• Status: Completed
• Enrollment: 206
• Est. completion date: June 2006
• Est. primary completion date: June 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Migraine Disorders
• Migraine Prophylaxis

Intervention

Drug:
• E2007

Other:
• Placebo

Locations

Country	Name	City	State
United States	Investigational Site	Chicago	Illinois
United States	Investigational Site	Greensboro	North Carolina
United States	Investigational Site	Houston	Texas
United States	Elkind Headache Center	Mount Vernon	New York
United States	Investigational Site	Oceanside	California
United States	Investigational Site	Santa Monica	California
United States	Investigational Site	Springfield	Missouri
United States	Investigational Site	Tampa	Florida
United States	Investigational Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Migraine Period Frequency Per 28 Days in Treatment Phase (LOCF)	A migraine period was defined as a migraine headache that started, ended, or recurred within 24 hours. If the headache persisted for longer than 24 hours, it was considered a new migraine period. Participants recorded the frequency of migraine period in diary. Efficacy analyses were performed using both the 24-hour and 48-hour rule for defining migraine periods. Data is presented as mean number of migraine period per 28 days +/- standard error. A negative change indicates a decrease in the number of migraine periods from baseline. LOCF = last observation carried forward (ie, observation from last phase with active treatment)	Baseline to Week 19	No
Secondary	Change From Baseline in Average Duration Per Migraine Attack in Treatment Phase (LOCF)	The duration of a migraine attack was the sum of the duration (in hours) of each migraine headache that was collapsed to form the migraine attack. The time between the offset of first migraine headache and the onset of the next migraine headache was not counted in the duration of migraine attack. The average duration of the migraine attacks in each phase was calculated as the total duration (in hours) of the migraine attacks during each phase, divided by the number of migraine attacks in the corresponding treatment phase. Efficacy analyses were performed using both the 24-hour and 48-hour rule. The data is presented as mean hours +/- standard error.	Baseline to Week 19	No
Secondary	Change From Baseline in Average Migraine Severity Per Migraine Attack in Treatment Phase (LOCF)	The average migraine attack severity in each treatment phase was calculated using the sum of the severity of migraine attacks during the treatment phase, divided by the number of qualified migraine attacks. The scale of severity for each migraine attack ranges from 0 to 100, with higher scores indicating increased migraine severity. Efficacy analyses were performed using both the 24-hour and 48-hour rule.	Baseline to Week 19	No
Secondary	Change From Baseline in Migraine Attack Frequency Per 28 Days in Treatment Phase (LOCF)	Qualified migraine headache was defined as two major subtypes: migraine without aura(headache that lasted 4-72 hours with at least two characteristics: unilateral location, pulsating quality, moderate/ severe pain intensity or aggravation by/ causing avoidance of routine physical activity and either nausea/ vomiting or photophobia,phonophobia); migraine with aura (attack with reversible focal neurological symptoms that usually precede or sometimes accompany the headache) per Migraine Criteria of the Headache Classification Committee of the International Headache Society. All of the qualified headaches, which occur after the initial qualified migraine headache, but within 24 hours of previous qualified migraine headache, were collapsed into one qualified migraine attack. Two qualified migraine attacks were considered to be distinct when the end of previous and the beginning of the next migraine attack were separated by at least 24/48 hours per 24/48 hour rule.	Baseline to Week 19	No
Secondary	Change From Baseline in Migraine Period Frequency Per 28 Days in Maintenance Phase	A migraine period was defined as a migraine headache that started, ended, or recurred within 24 hours. If the headache persisted for longer than 24 hours, it was considered a new migraine period. Efficacy analyses were performed using both the 24-hour and 48-hour rule for defining migraine periods. Data is presented as mean number of migraine period per 28 days +/- standard error. A negative change indicates a decrease in the number of migraine periods from baseline.	Baseline, Week 11 to Week 19	No
Secondary	Change From Baseline in Number of Days Requiring Symptomatic Rescue Medication Per 28 Days in Treatment Phase (LOCF)	The number of days requiring symptomatic rescue medication was calculated as the number of calender days during the migraine attack when the patient took one or more migraine rescue medications as recorded on the participant's diary. The calendar date(s) during which medication was taken will be used for calculations. Efficacy analyses were performed using both the 24-hour and 48-hour rule. The data is presented as mean days +/- standard error.	Baseline to Week 19	No
Secondary	Change From Baseline in Number of Days With Migraine Attack Per 28 Days in Treatment Phase (LOCF)	A migraine attack day was defined as a calendar day (from 0 hours to 24 hours) during which at least one migraine attack took place. If the migraine attack continues through midnight, each day will be counted separately. Efficacy analyses were performed using both the 24-hour and 48-hour rule. Data is presented as mean number of days with migraine attack per 28 days +/- standard error.	Baseline to Week 19	No
Secondary	Change From Baseline in Number of Participants With Patient Global Impression of Change (PGIC) of Migraine (LOCF)	The PGIC was a self-evaluation scale for each patient to assess his or her status compared to baseline in migraine headache frequency and intensity, the occurrence of adverse events, and overall functional status, measured on a 7-point scale. The scale ranges from "very much improved" with a score of 1 to "very much worse" with a score of 7. A responder is defined as being "very much improved" or "much improved". The data is presented as number of participants. LOCF = last observation carried forward (ie, observation from last phase with active treatment)	Baseline to Week 23	No
Secondary	Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Headache Pain Score	The MIDAS questionnaire was a participant assessed 7-item questionnaire designed to measure the impact of headache in the last 3 months. Based on question 7, pain due to headache was assessed on a scale of 0-10 with 0 being no pain and 10 being the most painful.	Baseline, Week 23	No
Secondary	Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Headaches	The MIDAS questionnaire was a participant assessed 7-item questionnaire designed to measure the impact of headache in the last 3 months. Based on question 6, the number of days with headache (Headache which lasted more than one day was counted as each day) was assessed. The data is presented as mean days +/- standard deviation.	Baseline, Week 23	No
Secondary	Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Less Housework	The MIDAS questionnaire was a participant assessed 7-item questionnaire designed to measure the impact of headache in the last 3 months. Based on question 4, the number of days when productivity in household work reduced by half of more because of a headache was assessed. The data is presented as mean days +/- standard deviation.	Baseline, Week 23	No
Secondary	Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Less Work or School	The MIDAS questionnaire was a participant assessed 7-item questionnaire designed to measure the impact of headache in the last 3 months. Based on question 2, the number of days with reduced productivity by at least half at school or work because of a headache was assessed. The data is presented as mean days +/- standard deviation.	Baseline, Week 23	No
Secondary	Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Missed Housework	The MIDAS questionnaire was a participant assessed 7-item questionnaire designed to measure the impact of headache in the last 3 months. Based on question 3, the number of days when participant skipped performing household chores or regular household activities because of a headache was assessed. The data is presented as mean days +/- standard deviation.	Baseline, Week 23	No
Secondary	Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Missed Non-Work Activities	The MIDAS questionnaire was a participant assessed 7-item questionnaire designed to measure the impact of headache in the last 3 months. Based on question 5, the number of days when participant miss leisure or social activities because of a headache was assessed. The data is presented as mean days +/- standard deviation.	Baseline, Week 23	No
Secondary	Change From Baseline of Migraine Disability Assessment Questionnaire Score (MIDAS) at Week 23: Missed Work or School	The MIDAS questionnaire was a participant assessed 7-item questionnaire designed to measure the impact of headache in the last 3 months. Based on question 1 , the number of missed work or school because of a headache was assessed. The data is presented as mean days +/- standard deviation.	Baseline, Week 23	No
Secondary	Percentage of Participants With a Greater Than or Equal to 50% Decrease in Migraine Attack Frequency Per 28 Days in Treatment Phase (LOCF)	Qualified migraine headache was defined as two major subtypes: migraine without aura(headache that lasted 4-72 hours with at least two characteristics: unilateral location, pulsating quality, moderate/ severe pain intensity or aggravation by/ causing avoidance of routine physical activity and either nausea/ vomiting or photophobia,phonophobia); migraine with aura (attack with reversible focal neurological symptoms that usually precede or sometimes accompany the headache) per Migraine Criteria of the Headache Classification Committee of the International Headache Society. All of the qualified headaches, which occur after the initial qualified migraine headache, but within 24 hours of previous qualified migraine headache, were collapsed into one qualified migraine attack. Two qualified migraine attacks were considered to be distinct when the end of previous and the beginning of the next migraine attack were separated by at least 24/48 hours per 24/48 hour rule.	Week 5 to Week 19	No
Secondary	Percentage of Participants With a Greater Than or Equal to 50% Decrease in Migraine Period Frequency Per 28 Days in Treatment Phase (LOCF)	A migraine period was defined as a migraine headache that started, ended, or recurred within 24 hours. If the headache persisted for longer than 24 hours, it was considered a new migraine period. Participants recorded the frequency of migraine period in diary. Efficacy analyses were performed using both the 24-hour and 48-hour rule for defining migraine periods. The data is presented as percentage of participants.	Week 5 to Week 19	No