Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache

Migraine Without Aura Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00311662
• Other study ID #: TON/01/05-CLIN
• Status: Completed
• Phase: Phase 2
• First received: April 4, 2006
• Last updated: August 28, 2009
• Start date: April 2006
• Est. completion date: October 2006

Study information

• Verified date: August 2009
• Source: Minster Research Ltd
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyDenmark: Danish Medicines AgencySouth Africa: Medicines Control CouncilHungary: National Institute of Pharmacy
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 124
• Est. completion date: October 2006
• Est. primary completion date: October 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Migraine Disorders
• Migraine with Aura
• Migraine Without Aura

Intervention

Drug:
• Tonabersat
Tablet 40mg daily for 12 weeks
• Placebo
Tablet once daily for 12 weeks

Locations

Country	Name	City	State
Denmark	Bispebjerg Hospital, Neurolgisk Afdeling N	Copenhagen
Denmark	Glostrup Amtssygehus, Neurologisk Ambulatorium N01	Copenhagen
Hungary	Kenézy Gyula County Hospital, Dept of Neurology	Debrecen
Hungary	Petz Aladár Megyei Oktató Kórház	Gyor
Hungary	Borsod Abauj Zemplén Megyei Kórház, Neurologiai Osztaly	Miskolc
Hungary	Zala County Hospital, Department of Cardiology	Zalaegerszeg
South Africa	Quinta-Med	Bloemfontein
South Africa	Chris Barnard Memorial Hospital	Cape Town
South Africa	St. Augustine's Medical Mews	Durban
South Africa	Francois Le Clus	Johannesburg
South Africa	Dr I Engelbrecht	Lyttleton
South Africa	Dr J Bouwer	Pretoria
South Africa	Intercare Corporate Office	Pretoria
South Africa	Little Company of Mary, Neurospinal Building	Pretoria
South Africa	Pretoria East Hospital, Neuro-Orthopaedic Unit	Pretoria
South Africa	SCION Clinical Research, 316 Medi-Clinic Heart Hospital	Pretoria
United Kingdom	The National Hospital for Neurology & Neurosurgery	London

Sponsors (1)

Lead Sponsor	Collaborator
Minster Research Ltd

Countries where clinical trial is conducted

Denmark,  Hungary,  South Africa,  United Kingdom, 

References & Publications (4)

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.

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. Cephalal — View Citation

Lauritzen M. Pathophysiology of the migraine aura. The spreading depression theory. Brain. 1994 Feb;117 ( Pt 1):199-210. Review. — View Citation

Tfelt-Hansen P, Block G, Dahlöf 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	Change in mean monthly number of migraine attacks from the baseline period to Month 3.		weeks 8-12 compared to weeks -4 to 0	No
Secondary	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	No
Secondary	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	No
Secondary	Speed of effect of treatment.		12 weeks	No
Secondary	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	No
Secondary	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	No
Secondary	Overall severity of migraine attacks occurring during the treatment period.		12 weeks	No
Secondary	Overall response to the question "How satisfied are you with the trial medication?"		12 weeks	No