Dose Ranging Study of the Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache

NCT00534560 | Completed Phase 2

• 1 other identifier: TON/03/07-CLIN
• Study Type: interventional
• Target: 542
• Locations: 0 countries
• Sites: N/A

Brief Summary

Primary objective: To investigate the efficacy and tolerability of two doses of tonabersat compared to placebo in the prophylaxis of migraine headache and to evaluate the longer term tolerability of tonabersat in an open label extension. Secondary objective(s): To obtain further data on the efficacy and dose response of tonabersat; To extend the safety and tolerability database of tonabersat; To obtain data on the pharmacokinetics of tonabersat.

Conditions

Migraine Without Aura; Migraine With Aura

Outcome Measures

Primary Outcomes (3)

• Reduction in the mean monthly number of migraine attacks over the last 2 months of the treatment period.

  4 weeks baseline and 20 weeks DB treatment

• Safety and tolerability: incidence of all AEs, serious adverse events (SAEs) and those leading to withdrawal of study medication, review of laboratory data, including hematology, biochemistry, and urinalysis, physical examinations, and vital signs.

  4 weeks baseline, 20 weeks DB treatment and 13 months open label extension

• Assessment of population pharmacokinetics for tonabersat - blood samples will be collected from a sub-population of patients

  20 weeks DB treatment

Secondary Outcomes (8)

• • Reduction in mean monthly migraine attacks during the last 4 months of the treatment period and during each month of the treatment period.

  4 weeks baseline and 20 weeks DB treatment

• • Proportion of patients defined as a responder i.e. difference between treatment groups in the number of patients with a reduction of at least 50% in the mean monthly frequency of migraine attacks during defined periods.

  4 week baseline and 20 weeks DB treatment

• • Reduction in mean monthly migraine headache days i.e. the difference between the two treatment groups in the reduction from baseline during defined periods

  4 weeks baseline and 20 weeks DB treatment

• • Proportion of patients defined as a responder i.e. difference between treatment groups in the number of patients with a reduction of at least 50% in the mean monthly number of migraine headache days during defined periods

  4 weeks baseline and 20 weeks DB treatment

• • Reduction in mean monthly consumption (number of days per month) of rescue medication during defined periods

  4 weeks baseline and 20 weeks DB treatment

Study Arms (3)

1

EXPERIMENTAL

Drug: Tonabersat

2

EXPERIMENTAL

Drug: Tonabersat

3

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tonabersat DRUG

Tablets, 4 week dose titration and 16 weeks treatment at target dose of 40 mg per day

Also known as: SB220453

1

Placebo DRUG

Tablets; 4 week dose titration with 16 weeks at target dose

3

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A signed and dated written informed consent is obtained prior to participation.
• Male or female patients between 18-65 years of age who are ambulatory and able to travel to the clinic; women of childbearing potential must be using a reliable form of contraception (contraceptive pill or double-barrier contraception - partner using condom and patient using spermicide, diaphragm, intra-uterine device or contraceptive sponge) for at least 2 months prior to enrolment and have a negative pregnancy test at screening. Women of childbearing potential must continue to practice birth control during and for at least two months after the study
• Patients with an established history of migraine of at least 1 year with or without aura meeting the diagnostic criteria of the International Classification of Headache Disorders - Edition 2.
• Patients should have experienced an average of at least 4 migraine attacks per month over the 3 months prior to entering the trial and at least 3 migraine attacks during the baseline period. Patients should report a maximum of 12 migraine headache days during the baseline period.

You may not qualify if:

• Patients with an onset of migraine according to the above criteria at age 50 years or more.
• Patients who experience \> 12 headache days during the baseline period.
• Patients who have failed to respond to adequate trials of 3 or more preventive medications.
• Overuse of acute migraine treatments defined as ≥ 15 medication days per month of which no more than 9 days includes ergots or triptans.
• Any woman who is pregnant, lactating or not using medically acceptable contraception.
• Patients taking other medications used as prophylaxis for migraine including topiramate, methysergide, anti-spasticity agents (e.g. tizanidine) and new generation antipsychotics (e.g. olanzapine) currently or within 1 month prior to entry to the trial.
• Patients taking any of the following medications: beta-blockers, tricyclic antidepressants, antiepileptic drugs, calcium channel blockers, or monoamine oxidase inhibitors during or within 1 month prior to the study; 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, herbal preparations (e.g. feverfew, butterwort and St John's Wort). Patients who have received parenteral administration of botulinum toxin within the previous 3 months will also be excluded.
• Patients who, in the opinion of the Investigator, have significant cerebrovascular disease (e.g. transient ischemic attacks, stroke) or significant cardiovascular disease within 30 days prior to screening.
• Patients suffering from any significant psychiatric disorder.
• Patient has a concomitant disease or condition that, in the opinion of the Investigator, could interfere with the conduct of the study or could put the patient at unacceptable risk.
• Patients with renal dysfunction, defined as a serum creatinine of greater then 2 mg/dL.
• Patients with hepatic dysfunction defined as a liver function test (AST, 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.
• Patient is a participating Investigator, sub-investigator, study coordinator, or employee of a participating Investigator, or is an immediate family member of the aforementioned.
• Any factor, which in the opinion of the Investigator would jeopardize the evaluation or safety or be associated with poor adherence to the protocol.

Sponsors & Collaborators

• Minster Research Ltd: lead

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

• Grosser K, Oelkers R, Hummel T, Geisslinger G, Brune K, Kobal G, Lotsch J. Olfactory and trigeminal event-related potentials in migraine. Cephalalgia. 2000 Sep;20(7):621-31. doi: 10.1111/j.1468-2982.2000.00094.x.

  PMID: 11128819 BACKGROUND

• Hu XH, Markson LE, Lipton RB, Stewart WF, Berger ML. Burden of migraine in the United States: disability and economic costs. Arch Intern Med. 1999 Apr 26;159(8):813-8. doi: 10.1001/archinte.159.8.813.

  PMID: 10219926 BACKGROUND

• Stewart WF, Lipton RB, Whyte J, Dowson A, Kolodner K, Liberman JN, Sawyer J. An international study to assess reliability of the Migraine Disability Assessment (MIDAS) score. Neurology. 1999 Sep 22;53(5):988-94. doi: 10.1212/wnl.53.5.988.

  PMID: 10496257 BACKGROUND

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

• Richard Lipton, MD

  Montefiore Medical Center Headache Unit

  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: September 24, 2007
• First Posted: September 26, 2007
• Study Start: October 1, 2007
• Primary Completion: November 1, 2008
• Study Completion: March 1, 2009
• Last Updated: March 31, 2009

Record last verified: 2009-03