Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache

This study has been completed.
Sponsor:
Information provided by:
Minster Research Ltd
ClinicalTrials.gov Identifier:
NCT00311662
First received: April 4, 2006
Last updated: August 28, 2009
Last verified: August 2009
  Purpose

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


Condition Intervention Phase
Migraine Without Aura
Migraine With Aura
Drug: Tonabersat
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Multi-centre, Parallel Group, Double-blind, Placebo Controlled Study of the Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache

Resource links provided by NLM:


Further study details as provided by Minster Research Ltd:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Speed of effect of treatment. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Overall severity of migraine attacks occurring during the treatment period. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Overall response to the question "How satisfied are you with the trial medication?" [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 124
Study Start Date: April 2006
Study Completion Date: October 2006
Primary Completion Date: October 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Tonabersat 40mg
Drug: Tonabersat
Tablet 40mg daily for 12 weeks
Other Name: SB220453
Placebo Comparator: 2 Drug: Placebo
Tablet once daily for 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00311662

Locations
Denmark
Glostrup Amtssygehus, Neurologisk Ambulatorium N01
Copenhagen, Denmark, Glostrup 2600
Bispebjerg Hospital, Neurolgisk Afdeling N
Copenhagen, Denmark, Kobenhavn NV 2400
Hungary
Kenézy Gyula County Hospital, Dept of Neurology
Debrecen, Hungary, Debrecen 1145
Petz Aladár Megyei Oktató Kórház
Gyor, Hungary, Gyor 9024
Borsod Abauj Zemplén Megyei Kórház, Neurologiai Osztaly
Miskolc, Hungary, Miskolc 3526
Zala County Hospital, Department of Cardiology
Zalaegerszeg, Hungary, Zalaegerszeg 8900
South Africa
Quinta-Med
Bloemfontein, South Africa, Bloemfontein 9301
Chris Barnard Memorial Hospital
Cape Town, South Africa, West Cape 8001
St. Augustine's Medical Mews
Durban, South Africa, KZ-Natal 4001
Francois Le Clus
Johannesburg, South Africa, Gauteng 1619
Dr I Engelbrecht
Lyttleton, South Africa, Guateng 0157
Little Company of Mary, Neurospinal Building
Pretoria, South Africa, Gauteng 0181
Pretoria East Hospital, Neuro-Orthopaedic Unit
Pretoria, South Africa, Gauteng 0044
SCION Clinical Research, 316 Medi-Clinic Heart Hospital
Pretoria, South Africa, Guateng 0002
Dr J Bouwer
Pretoria, South Africa, Gauteng 0082
Intercare Corporate Office
Pretoria, South Africa, Gauteng 0081
United Kingdom
The National Hospital for Neurology & Neurosurgery
London, United Kingdom, WC1N 3BG
Sponsors and Collaborators
Minster Research Ltd
Investigators
Principal Investigator: Peter Goadsby, MD The National Hospital for Neurology and Neurosurgery, London
  More Information

Publications:
Goadsby PJ, Ferrari MD, Csanyi A, Olesen J, Mills J on behalf of the Tonabersat TON-01-05 Study Group. Cephalalgia 29:742-750, 2009
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.

ClinicalTrials.gov Identifier: NCT00311662     History of Changes
Other Study ID Numbers: TON/01/05-CLIN
Study First Received: April 4, 2006
Last Updated: August 28, 2009
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Denmark: Danish Medicines Agency
South Africa: Medicines Control Council
Hungary: National Institute of Pharmacy

Additional relevant MeSH terms:
Headache
Migraine Disorders
Migraine with Aura
Migraine without Aura
Pain
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases

ClinicalTrials.gov processed this record on April 15, 2014