DP-VPA for Migraine Prophylaxis, a Pilot Efficacy Study

Study Overview
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Brief Summary
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The study will evaluate if DP-VPA, a derivative of valproate (a drug that is commonly used for the prevention of migraine attacks), can reduce the rate of migraine attacks. Migraine patients will take DP-VPA or placebo (an inactive look-alike drug) every morning and will have to report any migraine attacks they have during the study's 18-week follow up.

Detailed Description
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The multi-center trial has a double-blind, randomized, placebo-controlled, parallel-group design and will be carried out in Israel. Approximately 40 adult subjects with migraine will be randomly assigned (1:1) to either DP-VPA (maximum of 900mg/day) or placebo. Active and placebo will be administered orally and once-daily on an add-on basis, i.e. other permissible ongoing medications will be continued. Total study duration per subject will be 18 weeks. Subjects will report on their migraine attacks frequency and other attack characteristics using weekly diaries.

Official Title
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Double-Blind, Randomized, Placebo-Controlled, Parallel-Group, Two-Arm, Multi-Center Phase II Trial to Assess the Safety, Tolerability, and Efficacy of DP-VPA (up to 900 mg) Once Daily for 10 Weeks in Adult Subjects With Migraine

Conditions
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Migraine

Intervention / Treatment
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* Drug: DP-VPA
* Drug: DP-VPA Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria (abridged) Male and female subjects with migraine with or without aura fulfilling the diagnostic criteria of the International Classification of Headache Disorders 3 to 6 migraine attacks per month Concomitant prophylactic migraine treatment with a beta-blocker or amitriptyline that has been stable in the proceeding 3 months. No changes in this concomitant treatment will be allowed until the end of study follow-up. Exclusion criteria (abridged)Chronic migraine (>15 days of migraine/ month). Migraine complicated by medication-overuse headache. Allergy or hypersensitivity to valproic acid, valproate sodium, or soy. Known contraindications to valproic acid. Pregnancy. Breastfeeding female subjects. Subjects with significant hepatic dysfunction indicated by SGOT or SGPT >3 times the upper limit of normal at screening. Renal impairment indicated by serum creatinine >1.5mg/dL at screening. Potentially fertile and sexually active women who do not practice reliable contraception. Men who do not practice reliable barrier contraception. Concomitant use of antipsychotic, antidepressant or antiepileptic therapy - with the exception of amitriptyline - within 1 month of screening, or a medical condition that is likely to require such treatment during the trial participation. An active central nervous system disease deemed to be unstable or progressive during the course of the study that may confound the interpretation of the study results. Any medical disorder that may makes the subject unlikely to fully complete the study- Blood coagulation disorder. Concomitant drugs known to interact with VPA.- Alcohol or other drugs abuse. Therapy with another investigational product within 30 days prior start of study. Concomitant participation in another trial or study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>DP-VPA | Drug: DP-VPA<br>* DP-VPA dose escalation to 900mg, then continued for 8 weeks<br>|
| Placebo Comparator: B<br> | Drug: DP-VPA Placebo<br>* Matching Placebo to Active, dose escalation, then continued for 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Migraine attacks frequency |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Migraine days |  | 6 months | 
| Responders (subjects with >50% decrease in migraine frequency) |  | 6 months | 
| Triptan consumption |  | 6 months |