Migraine Without AuraPhase 2TEMPUSNCT00534560
Dose Ranging Study of the Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache
A Phase 2 study testing Tonabersat in people with Migraine Without Aura and Migraine With Aura, run by Minster Research Ltd.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Migraine Without Aura, Migraine With Aura
- What is being tested?
- Tonabersat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 542 participants
- Where
- No sites listed yet
- Study dates
- Oct 2007to Mar 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
- The patient's primary care physician recommends the patient should not take part in the study.
About this study
Official title: Multi-Centre, Parallel Group, Double-Blind, Placebo Controlled, Dose Ranging Study of the Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache and Open Label Extension
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.
Read the detailed description
A multi-centre, double-blind, placebo controlled, randomized, parallel group, dose ranging study to investigate the efficacy and tolerability of two different target doses of tonabersat and placebo in the prophylaxis of migraine. Following initial screening patients will enter a 4 week baseline assessment period, prior to randomization to one of three treatment groups. Subsequently patients will be allocated, according to the predetermined randomization schedule, to treatment with placebo or a target dose of tonabersat 40 mg/day or 80 mg/day in a 20 week treatment period. A dose titration regimen will be employed over a period of 4 weeks and treatment will then be maintained for a further 16 weeks. During the baseline assessment period and the treatment period patients will maintain a daily record (diary data) of the occurrence of migraine headache, the severity of an attack, the presence/absence of a preceding aura, other symptoms associated with the migraine and details of the use of rescue medication (patients will be permitted to use their usual symptomatic/acute treatment as rescue medication throughout the trial). Patients will attend the clinic for assessment and collection of blood and urine samples for laboratory analysis, and a sub-population of patients will participate in a pharmacokinetic study. A total of 7 visits are planned during the randomized double-blind treatment period.
On completion of the randomized double-blind treatment period all patients will be offered the opportunity to enter an open label extension study where all patients receive tonabersat. A dose titration regimen will be employed over a period of 1 month and the final assigned dose of tonabersat (40, 60 or 80 mg/day) will be continued for the next 12 months. During the open label extension patients will attend the clinic for regular assessment of migraine status and safety. A total of 5 visits are planned.
- Conditions
- Migraine Without Aura, Migraine With Aura
- Being tested
- Tonabersat, Placebo
- Medical subject headings
- Migraine without Aura, Migraine with Aura
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TonabersatDrug
Also called SB220453
Tablets, 4 week dose titration and 16 weeks treatment at target dose of 40 mg per day
TonabersatDrug
Also called SB220453
Tablets: 4 week titration and 16 weeks at target dose of 80 mg per day
PlaceboDrug
Tablets; 4 week dose titration with 16 weeks at target dose
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Tonabersat |
| 2 | Experimental | Not described Receives: Drug: Tonabersat |
| 3 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in the mean monthly number of migraine attacks over the last 2 months of the treatment period.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 4 weeks baseline and 20 weeks DB treatment
• Reduction in mean monthly consumption (number of days per month) of rescue medication during defined periods
Measured: 4 weeks baseline and 20 weeks DB treatment
• Onset of action (defined as first monthly period for which a significant difference between treatment groups is observed and is then maintained over the rest of the treatment period).
Measured: 4 weeks baseline and 20 weeks DB treatment
• Difference between treatment groups in the maximum severity of migraine attacks occurring during defined periods
Measured: 4 weeks baseline and 20 weeks DB treatment
• Summary of the Migraine Disability Assessment Score (MIDAS) assessments.
Measured: 4 weeks baseline, 20 weeks DB treatment and 13 months open label extension
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2007 (estimated)
- Study startOct 2007
- Primary completionNov 2008
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Migraine Without AuraStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 542 participants (actual)
Sponsor and investigators
- Lead sponsor
- Minster Research Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Richard Lipton, MD, Principal investigator, Montefiore Medical Center Headache Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00534560
- Sponsor's protocol ID
- TON/03/07-CLIN
- Acronym
- TEMPUS
- Status last verified
- Mar 2009
- First submitted
- 24 Sep 2007
- Last updated
- 31 Mar 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 11167908Grosser 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.
PubMed 11128819Hu 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.
PubMed 10219926Stewart 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.
PubMed 10496257
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-Centre, Parallel Group, Double-Blind, Placebo Controlled, Dose Ranging Study of the Efficacy and Tolerability of Tonabersat in the Prophylaxis of Migraine Headache and Open Label Extension
- ClinicalTrials.gov ID
- NCT00534560
- Acronym / sponsor ID
- TEMPUS / TON/03/07-CLIN
- Conditions
- Migraine Without Aura, Migraine With Aura
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 542 participants (actual)
- Lead sponsor
- Minster Research LtdIndustry (pharma, biotech, devices)
- Study start
- Oct 2007
- Primary completion
- Nov 2008 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 26 Sep 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A multi-centre, double-blind, placebo controlled, randomized, parallel group, dose ranging study to investigate the efficacy and tolerability of two different target doses of tonabersat and placebo in the prophylaxis of migraine. Following initial screening patients will enter a 4 week baseline assessment period, prior to randomization to one of three treatment groups. Subsequently patients will be allocated, according to the predetermined randomization schedule, to treatment with placebo or a target dose of tonabersat 40 mg/day or 80 mg/day in a 20 week treatment period. A dose titration regimen will be employed over a period of 4 weeks and treatment will then be maintained for a further 16 weeks. During the baseline assessment period and the treatment period patients will maintain a daily record (diary data) of the occurrence of migraine headache, the severity of an attack, the presence/absence of a preceding aura, other symptoms associated with the migraine and details of the use of rescue medication (patients will be permitted to use their usual symptomatic/acute treatment as rescue medication throughout the trial). Patients will attend the clinic for assessment and collection of blood and urine samples for laboratory analysis, and a sub-population of patients will participate in a pharmacokinetic study. A total of 7 visits are planned during the randomized double-blind treatment period.
On completion of the randomized double-blind treatment period all patients will be offered the opportunity to enter an open label extension study where all patients receive tonabersat. A dose titration regimen will be employed over a period of 1 month and the final assigned dose of tonabersat (40, 60 or 80 mg/day) will be continued for the next 12 months. During the open label extension patients will attend the clinic for regular assessment of migraine status and safety. A total of 5 visits are planned.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Tonabersat |
| 2 | Experimental | Drug: Tonabersat |
| 3 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TonabersatAlso: SB220453Tablets, 4 week dose titration and 16 weeks treatment at target dose of 40 mg per day | Drug | 1 |
| TonabersatAlso: SB220453Tablets: 4 week titration and 16 weeks at target dose of 80 mg per day | Drug | 2 |
| PlaceboTablets; 4 week dose titration with 16 weeks at target dose | Drug | 3 |
Primary outcome
Reduction in the mean monthly number of migraine attacks over the last 2 months of the treatment period.
Time frame: 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.
Time frame: 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
Time frame: 20 weeks DB treatment
8 secondary outcomes
• Reduction in mean monthly migraine attacks during the last 4 months of the treatment period and during each month of the treatment period.
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 4 weeks baseline and 20 weeks DB treatment
• Reduction in mean monthly consumption (number of days per month) of rescue medication during defined periods
Time frame: 4 weeks baseline and 20 weeks DB treatment
• Onset of action (defined as first monthly period for which a significant difference between treatment groups is observed and is then maintained over the rest of the treatment period).
Time frame: 4 weeks baseline and 20 weeks DB treatment
• Difference between treatment groups in the maximum severity of migraine attacks occurring during defined periods
Time frame: 4 weeks baseline and 20 weeks DB treatment
• Summary of the Migraine Disability Assessment Score (MIDAS) assessments.
Time frame: 4 weeks baseline, 20 weeks DB treatment and 13 months open label extension
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2009.
- Background: PubMed 11167908Tfelt-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.
- Background: PubMed 11128819Grosser 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.
- Background: PubMed 10219926Hu 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.
- Background: PubMed 10496257Stewart 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Lipton, MD principal investigator
Montefiore Medical Center Headache Unit
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tonabersat in people with Migraine Without Aura and Migraine With Aura, run by Minster Research Ltd.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2009. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in the mean monthly number of migraine attacks over the last 2 months of the treatment period. (time frame: 4 weeks baseline and 20 weeks DB treatment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00534560, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2009.