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Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache

Primary Purpose

Migraine Without Aura, Migraine With Aura

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tonabersat
Placebo
Sponsored by
Minster Research Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Migraine Without Aura

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Glostrup Amtssygehus, Neurologisk Ambulatorium N01
  • Bispebjerg Hospital, Neurolgisk Afdeling N
  • Kenézy Gyula County Hospital, Dept of Neurology
  • Petz Aladár Megyei Oktató Kórház
  • Borsod Abauj Zemplén Megyei Kórház, Neurologiai Osztaly
  • Zala County Hospital, Department of Cardiology
  • Quinta-Med
  • Chris Barnard Memorial Hospital
  • St. Augustine's Medical Mews
  • Francois Le Clus
  • Dr I Engelbrecht
  • Pretoria East Hospital, Neuro-Orthopaedic Unit
  • Intercare Corporate Office
  • Dr J Bouwer
  • Little Company of Mary, Neurospinal Building
  • SCION Clinical Research, 316 Medi-Clinic Heart Hospital
  • The National Hospital for Neurology & Neurosurgery

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

1

2

Arm Description

Tonabersat 40mg

Outcomes

Primary Outcome Measures

Change in the mean monthly number of migraine headache days from the baseline period to Month 3.
Incidence of all adverse events (AEs), serious AEs and AEs leading to withdrawal of trial medication, clinical laboratory tests, vital signs and physical examination

Secondary Outcome Measures

Change in the mean monthly number of migraine headache days from the baseline period to across the whole treatment period.
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.
Change in mean monthly number of migraine attacks from the baseline period to Month 3.
Change in mean monthly number of migraine attacks from the baseline period to across the whole treatment period.
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.
Speed of effect of treatment.
Change in the mean monthly consumption of rescue medication from the baseline period to Month 3.
Change in the mean monthly consumption of rescue medication from the baseline period to across the whole treatment period.
Overall severity of migraine attacks occurring during the treatment period.
Overall response to the question "How satisfied are you with the trial medication?"

Full Information

First Posted
April 4, 2006
Last Updated
August 28, 2009
Sponsor
Minster Research Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT00311662
Brief Title
Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache
Official Title
Multi-centre, Parallel Group, Double-blind, Placebo Controlled Study of the Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache
Study Type
Interventional

2. Study Status

Record Verification Date
August 2009
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
October 2006 (Actual)
Study Completion Date
October 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Minster Research Ltd

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Migraine Without Aura, Migraine With Aura

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
124 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Tonabersat 40mg
Arm Title
2
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Tonabersat
Other Intervention Name(s)
SB220453
Intervention Description
Tablet 40mg daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Tablet once daily for 12 weeks
Primary Outcome Measure Information:
Title
Change in the mean monthly number of migraine headache days from the baseline period to Month 3.
Time Frame
weeks 8 to 12 compared to weeks -4 to 0
Title
Incidence of all adverse events (AEs), serious AEs and AEs leading to withdrawal of trial medication, clinical laboratory tests, vital signs and physical examination
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Change in the mean monthly number of migraine headache days from the baseline period to across the whole treatment period.
Time Frame
weeks 0-12 compared to weeks -4 to 0
Title
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.
Time Frame
weeks 8-12 compared to weeks -4 to 0
Title
Change in mean monthly number of migraine attacks from the baseline period to Month 3.
Time Frame
weeks 8-12 compared to weeks -4 to 0
Title
Change in mean monthly number of migraine attacks from the baseline period to across the whole treatment period.
Time Frame
weeks 0 to 12 compared to weeks -4 to 0
Title
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.
Time Frame
weeks 8-12 compared to weeks -4 to 0
Title
Speed of effect of treatment.
Time Frame
12 weeks
Title
Change in the mean monthly consumption of rescue medication from the baseline period to Month 3.
Time Frame
weeks 8 to 12 compared to weeks -4 to 0
Title
Change in the mean monthly consumption of rescue medication from the baseline period to across the whole treatment period.
Time Frame
weeks 0 to 12 comoared to weeks -4 to 0
Title
Overall severity of migraine attacks occurring during the treatment period.
Time Frame
12 weeks
Title
Overall response to the question "How satisfied are you with the trial medication?"
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Goadsby, MD
Organizational Affiliation
The National Hospital for Neurology and Neurosurgery, London
Official's Role
Principal Investigator
Facility Information:
Facility Name
Glostrup Amtssygehus, Neurologisk Ambulatorium N01
City
Copenhagen
ZIP/Postal Code
Glostrup 2600
Country
Denmark
Facility Name
Bispebjerg Hospital, Neurolgisk Afdeling N
City
Copenhagen
ZIP/Postal Code
Kobenhavn NV 2400
Country
Denmark
Facility Name
Kenézy Gyula County Hospital, Dept of Neurology
City
Debrecen
ZIP/Postal Code
Debrecen 1145
Country
Hungary
Facility Name
Petz Aladár Megyei Oktató Kórház
City
Gyor
ZIP/Postal Code
Gyor 9024
Country
Hungary
Facility Name
Borsod Abauj Zemplén Megyei Kórház, Neurologiai Osztaly
City
Miskolc
ZIP/Postal Code
Miskolc 3526
Country
Hungary
Facility Name
Zala County Hospital, Department of Cardiology
City
Zalaegerszeg
ZIP/Postal Code
Zalaegerszeg 8900
Country
Hungary
Facility Name
Quinta-Med
City
Bloemfontein
ZIP/Postal Code
Bloemfontein 9301
Country
South Africa
Facility Name
Chris Barnard Memorial Hospital
City
Cape Town
ZIP/Postal Code
West Cape 8001
Country
South Africa
Facility Name
St. Augustine's Medical Mews
City
Durban
ZIP/Postal Code
KZ-Natal 4001
Country
South Africa
Facility Name
Francois Le Clus
City
Johannesburg
ZIP/Postal Code
Gauteng 1619
Country
South Africa
Facility Name
Dr I Engelbrecht
City
Lyttleton
ZIP/Postal Code
Guateng 0157
Country
South Africa
Facility Name
Pretoria East Hospital, Neuro-Orthopaedic Unit
City
Pretoria
ZIP/Postal Code
Gauteng 0044
Country
South Africa
Facility Name
Intercare Corporate Office
City
Pretoria
ZIP/Postal Code
Gauteng 0081
Country
South Africa
Facility Name
Dr J Bouwer
City
Pretoria
ZIP/Postal Code
Gauteng 0082
Country
South Africa
Facility Name
Little Company of Mary, Neurospinal Building
City
Pretoria
ZIP/Postal Code
Gauteng 0181
Country
South Africa
Facility Name
SCION Clinical Research, 316 Medi-Clinic Heart Hospital
City
Pretoria
ZIP/Postal Code
Guateng 0002
Country
South Africa
Facility Name
The National Hospital for Neurology & Neurosurgery
City
London
ZIP/Postal Code
WC1N 3BG
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
11167908
Citation
Tfelt-Hansen P, Block G, Dahlof C, Diener HC, Ferrari MD, Goadsby PJ, Guidetti V, Jones B, Lipton RB, Massiou H, Meinert C, Sandrini G, Steiner T, Winter PB; International Headache Society Clinical Trials Subcommittee. Guidelines for controlled trials of drugs in migraine: second edition. Cephalalgia. 2000 Nov;20(9):765-86. doi: 10.1046/j.1468-2982.2000.00117.x. No abstract available.
Results Reference
background
PubMed Identifier
7908596
Citation
Lauritzen M. Pathophysiology of the migraine aura. The spreading depression theory. Brain. 1994 Feb;117 ( Pt 1):199-210. doi: 10.1093/brain/117.1.199.
Results Reference
background
Citation
Committee for Proprietary Medicinal Products. Note for guidance on clinical investigation of medicinal products for the treatment of migraine, CPMP/EWP/788/01/Final. London, 17 December 2003.
Results Reference
background
PubMed Identifier
19222510
Citation
Goadsby PJ, Ferrari MD, Csanyi A, Olesen J, Mills JG; Tonabersat TON-01-05 Study Group. Randomized, double-blind, placebo-controlled, proof-of-concept study of the cortical spreading depression inhibiting agent tonabersat in migraine prophylaxis. Cephalalgia. 2009 Jul;29(7):742-50. doi: 10.1111/j.1468-2982.2008.01804.x. Epub 2009 Feb 13.
Results Reference
result

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Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache

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