Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache

Study Overview
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Brief Summary
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Overall trial objectives: Can treatment with tonabersat reduce the number of days with a migraine headache in patients who suffer from frequent migraine attacks How well tolerated is treatment with tonabersat The study is based on the hypothesis that the unique mechanism of action of tonabersat will inhibit some of the early events in the generation of migraine and so be effective as prophylactic treatment

Official Title
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Multi-centre, Parallel Group, Double-blind, Placebo Controlled Study of the Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache

Conditions
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Migraine Without Aura, Migraine With Aura

Intervention / Treatment
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* Drug: Tonabersat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An established history of migraine of at least one year, with or without aura, meeting the diagnostic criteria of the International Classification of Headache Disorders, and experience between four and 14 migraine headache days per month; headache days should be experienced within at least two and no more than six migraine attacks per month. Women of child bearing potential must be using a reliable form of contraception (defined in the protocol) for at least three months prior to enrolment with contraception maintained for at least 7 days after the last dose of study medication and they must have a negative pregnancy test at screening with no intention of becoming pregnant during the study period. Exclusion Criteria: Patients with a diagnosis of migraine according to the diagnostic criteria of the International Classification of Headache Disorders at age 50 years or more. Experience frequent non-migraine headache Patients with pure menstrual migraine defined as patients in whom migraine attacks occur exclusively on Day 1 +/- 2 (i.e. Days -2 to +3) of menstruation in at least two out of three menstrual cycles and at no other times of the cycle. Patients with other significant central nervous system disorders in the opinion of the investigator. Failure to respond to more than two adequately dosed (i.e. recommended total daily dose and of sufficient duration) migraine prophylactic medications. Overuse of acute migraine treatments defined as more than 14 medication days per month with analgesics and opioids and nine medication days per month of ergots or triptans. Prophylactic treatment within two months prior to entry to the trial. Patients taking any of the following medications: beta-blockers (during the last two months), tricyclic antidepressants (during the last two months), antiepileptic drugs (during the last two months), calcium channel blockers (during the last two months), monoamine oxidase inhibitors (during the last two months), daily oral NSAIDs, daily paracetamol, high dose magnesium supplements (600 mg/day), daily multivitamin preparations containing more than 10 mg riboflavin, daily use of oral corticosteroids and daily herbal preparations (e.g. feverfew, butterwort and St John's Wort). Parenteral administration of Botulinum toxin is also excluded. Patients taking other medications used as prophylaxis for migraine including methysergide, anti spasticity agents (e.g. tizanidine) and the new generation antipsychotics (e.g. olanzapine) currently or within the previous two months should also be excluded. Patients who, in the opinion of the investigator, have significant cerebrovascular disease, e.g. transient ischaemic attacks, stroke. Patients who, in the opinion of the investigator, have clinically significant cardiovascular disease. Patients suffering from a current clinical diagnosis of major depressive disorder or schizophrenia. Patients with renal dysfunction, defined as a serum creatinine of greater than 125% of the upper limit of normal for their age group. Patients with hepatic dysfunction defined as a liver function test (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase, bilirubin) of greater than twice the upper limit of normal for their age group. Patients with known alcohol or other substance abuse. Failure to complete the diary card during the baseline period. Participation in another clinical trial in the previous four weeks. Any women who is pregnant, lactating or not using medically acceptable contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Tonabersat 40mg | Drug: Tonabersat<br>* Tablet 40mg daily for 12 weeks<br>* Other names: SB220453;|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Tablet once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the mean monthly number of migraine headache days from the baseline period to Month 3. |  | weeks 8 to 12 compared to weeks -4 to 0 | 
| Incidence of all adverse events (AEs), serious AEs and AEs leading to withdrawal of trial medication, clinical laboratory tests, vital signs and physical examination |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the mean monthly number of migraine headache days from the baseline period to across the whole treatment period. |  | weeks 0-12 compared to weeks -4 to 0 | 
| Proportion of patients defined as a responder, i.e. those with a reduction of at least 50% in the mean monthly number of migraine headache days in the third month of treatment and over the whole treatment period. |  | weeks 8-12 compared to weeks -4 to 0 | 
| Change in mean monthly number of migraine attacks from the baseline period to Month 3. |  | weeks 8-12 compared to weeks -4 to 0 | 
| Change in mean monthly number of migraine attacks from the baseline period to across the whole treatment period. |  | weeks 0 to 12 compared to weeks -4 to 0 | 
| Proportion of patients defined as a responder, i.e. those with a reduction of at least 50% in the mean monthly frequency of migraine attacks in the third month of treatment and over the whole treatment period. |  | weeks 8-12 compared to weeks -4 to 0 | 
| Speed of effect of treatment. |  | 12 weeks | 
| Change in the mean monthly consumption of rescue medication from the baseline period to Month 3. |  | weeks 8 to 12 compared to weeks -4 to 0 | 
| Change in the mean monthly consumption of rescue medication from the baseline period to across the whole treatment period. |  | weeks 0 to 12 comoared to weeks -4 to 0 | 
| Overall severity of migraine attacks occurring during the treatment period. |  | 12 weeks | 
| Overall response to the question How satisfied are you with the trial medication? |  | 12 weeks |