An Evaluation Of The Efficacy And Safety Of Donepezil Hydrochloride (E2020) In Migraine Prophylaxis

Study Overview
=================
Brief Summary
-----------------
The purpose of this extension study was to evaluate the safety and efficacy of donepezil hydrochloride after extended use in migraine prophylaxis. Efficacy will continue to be evaluated.

Official Title
-----------------
An Open-Label, Multicenter, One-Year Extension Of The Evaluation Of The Efficacy And Safety Of Donepezil Hydrochloride (E2020) In Migraine Prophylaxis

Conditions
-----------------
Migraine Headache

Intervention / Treatment
-----------------
* Drug: Aricept (donepezil hydrochloride)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patient must have completed study E2020-A001-211 according to the protocol. Male and female patients between 18-65 years of age. Women of childbearing potential practiced effective contraception (e.g., abstinence, intra-uterine device (IUD) or barrier method plus hormonal method), had a negative urine -hCG at Week 0, and be willing to remain on their current form of contraception for the duration of the study. Pregnant and/or lactating females were to be excluded. Patients of any race who were in generally good health. Patient was willing to participate, and has provided written informed consent prior to being exposed to any study-related procedures. Exclusion Criteria: Evidence of any clinically significant disorder which was being evaluated medically, and which had not been shown to be stable on medications or other treatment(s) for a period of at least 3 months, including active or uncontrolled tumors, non-trauma related cerebrovascular accidents, gastrointestinal, renal, hepatic, endocrine or pulmonary disease, cardiovascular system disease or known collagen vascular disease (e.g., systemic lupus erythematosus). Hypertension was medication controlled (supine diastolic BP < 95 mmHg). Cardiac disease (angina pectoris, congestive heart failure or arrhythmias) was stable on appropriate medication for 6 months. No elective surgical procedures were allowed during the course of the study. Patients with a recent history (</= 2 years) of or on active treatment for any hematologic/oncologic disorders (other than basal or squamous cell carcinoma of the skin). Patients with a serious central nervous system (CNS) disorder (e.g., neoplasm, infection, demyelinating disease, degenerative neurological disease such as Alzheimer's disease, Parkinson's disease, vascular dementia, or any other progressive CNS disease) or who either evidence focal neurological signs or symptoms by examination or history (e.g., papilledema) or who evidence transient neurological symptoms without an ensuing headache. Any medical or psychiatric (e.g., severe depression, psychosis, bipolar disorder) condition which, in the opinion of the Investigator, made the patient unsuitable for the study. History of chronic alcoholism or drug abuse as defined by DSM-IV criteria or patients who had previously been hospitalized and/or treated for substance abuse within the past one year. History of overuse (> 12 days per four week period on average) of acute headache medications including analgesics, opioids, Non-steroidal anti-inflammatory drugs (NSAIDs), butalbital containing compounds, ergots and triptans within the past one (1) year. Patients who were taking any prior or concomitant medications, as defined in the Protocol (Appendix 16.1.1), during the study. Patients who were unwilling or unable to fulfill the requirements of the study. Patients with known hypersensitivity to piperidine derivatives. Patients who had taken a cholinesterase inhibitor (e.g., donepezil, tacrine, rivastigmine, galantamine, metrifonate) for the acute or prophylactic treatment of migraines in the past (excluding E2020-A001-211) or who were currently taking a cholinesterase inhibitor for any other indication. Patients who had taken any unapproved prior or concomitant medications. In particular, patients were not allowed to take beta-blockers, tricyclic antidepressants, calcium channel blockers, monoamine oxidase inhibitors, valproate, methysergide, cyproheptadine or any other ongoing prophylactic treatment for migraines while participating in this study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Aricept (donepezil hydrochloride)<br>* Donepezil hydrochloride tablet: initial 5 mg/day dose was taken orally, once a day. At Week 4 visit, the dose was increased to 10 mg/day at the discretion of the investigator.<br>* Other names: donepezil hydrochloride;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: physical examination, vital signs measurement, clinical laboratory evaluation, 12-lead ECG measurement, adverse event (AE) evaluation. |  | Every visit up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients experiencing ≥ 50% reduction in migraine frequency per month (responders). |  | Weeks 4, 16, 28, 40 and 52. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
migraine, headache