Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache

NCT00311662 | Completed Phase 2

• 1 other identifier: TON/01/05-CLIN
• Study Type: interventional
• Target: 124
• Locations: 4 countries
• Sites: 17

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

Conditions

Migraine Without Aura; Migraine With Aura

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• 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

Study Arms (2)

1

EXPERIMENTAL

Tonabersat 40mg

Drug: Tonabersat

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tonabersat DRUG

Tablet 40mg daily for 12 weeks

Also known as: SB220453

1

Placebo DRUG

Tablet once daily for 12 weeks

2

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Minster Research Ltd: lead

Study Sites (17)

Glostrup Amtssygehus, Neurologisk Ambulatorium N01

Copenhagen, Glostrup 2600, Denmark

Location

Bispebjerg Hospital, Neurolgisk Afdeling N

Copenhagen, Kobenhavn NV 2400, Denmark

Location

Kenézy Gyula County Hospital, Dept of Neurology

Debrecen, Debrecen 1145, Hungary

Location

Petz Aladár Megyei Oktató Kórház

Győr, Gyor 9024, Hungary

Location

Borsod Abauj Zemplén Megyei Kórház, Neurologiai Osztaly

Miskolc, Miskolc 3526, Hungary

Location

Zala County Hospital, Department of Cardiology

Zalaegerszeg, Zalaegerszeg 8900, Hungary

Location

Quinta-Med

Bloemfontein, Bloemfontein 9301, South Africa

Location

Chris Barnard Memorial Hospital

Cape Town, West Cape 8001, South Africa

Location

St. Augustine's Medical Mews

Durban, KZ-Natal 4001, South Africa

Location

Francois Le Clus

Johannesburg, Gauteng 1619, South Africa

Location

Dr I Engelbrecht

Lyttleton, Guateng 0157, South Africa

Location

Pretoria East Hospital, Neuro-Orthopaedic Unit

Pretoria, Gauteng 0044, South Africa

Location

Intercare Corporate Office

Pretoria, Gauteng 0081, South Africa

Location

Dr J Bouwer

Pretoria, Gauteng 0082, South Africa

Location

Little Company of Mary, Neurospinal Building

Pretoria, Gauteng 0181, South Africa

Location

SCION Clinical Research, 316 Medi-Clinic Heart Hospital

Pretoria, Guateng 0002, South Africa

Location

The National Hospital for Neurology & Neurosurgery

London, WC1N 3BG, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 11167908 BACKGROUND

• 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.

  PMID: 7908596 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 19222510 RESULT

MeSH Terms

Conditions

Migraine without Aura; Migraine with Aura

Interventions

tonabersat

Condition Hierarchy (Ancestors)

Migraine Disorders; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Peter Goadsby, MD

  The National Hospital for Neurology and Neurosurgery, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 4, 2006
• First Posted: April 6, 2006
• Study Start: April 1, 2006
• Primary Completion: October 1, 2006
• Study Completion: October 1, 2006
• Last Updated: August 31, 2009

Record last verified: 2009-08

Locations

HU (4); DK (2); GB (1); ZA (10)