E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate whether the new injection procedure is safe and tolerable to the patients |
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E.2.2 | Secondary objectives of the trial |
To 1) see whether there is indication of any effect at all, 2) evaluate whether, in a later blinded study, there is the possibility of unblinding through side effects, and 3) obtain data on the variability of the main efficacy data to enable a power calculation for a future double blind, randomized, placebocontrolled trial. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Men or women between 18 and 65 years with chronic migraine, as defined in the ICHD-3. 2) CM should have been present for at least ½ year prior to evaluation for study inclusion. 3) For fertile women: Negative urine pregnancy test and use of reliable means of contraception 4) Signed informed consent
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E.4 | Principal exclusion criteria |
1)Patients with diseases that are contraindications for use of BoNT-A (Myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, other diseases interfering with neuromuscular function) or allergy to BoNT-A 2)Other primary or secondary headache disorder, including medication overuse headache (MOH). This means that at least one attempt to withdraw acute medication should have been performed earlier, but without success 3)Severe depression or other psychiatric disorder that may interfere with the treatment. 4)Abuse of alcohol or illicit drugs 5)Use of more than one headache prophylactic medication, or change in type and dose of prophylactic medication < 28 days before start of baseline period 6)Previous exposure at any time to any botulinum toxin serotype 7)Infection at one or more injection site(s) 8) Subject received extracranial nerve block, cervical facet injection, or other interventional procedure for headache within the prior 3 months. 9)Use of opioids or barbiturate containing medication(s) > 10 days per month within the preceding 3 months 10)Participating in another trial that might affect the current study 11) In the opinion of the investigator, the patient should not participate (e.g. not able to comply with study procedures).
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E.5 End points |
E.5.1 | Primary end point(s) |
I: Tolerability and safety of injection procedure: Right after the injection the doctor will fill out a form about duration of injection (minutes), bleeding and other problems. The patient will indicate on a VAS scale the level of pain of the procedure.
II: Side effects: Patient will indicate any medical problems and complaints in the headache diary. At each scheduled or unscheduled contact (visit or telephone), patients will be asked an open question about any medical problems that have occurred since the last contact
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
I: On the day of injection
II:The diary is kept throughout the study, from four weeks before till 12 weeks after injections. The patient will also be asked about this at telphone calls from the study nurse 1-2 weeks and 8-9 weeks after injection, and at the final visit to the doctor 12 weeks after injection.
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E.5.2 | Secondary end point(s) |
I: Patients will be asked at before each consultation to look in the mirror to detect differences in ability to make forehead wrinkles (no, mild, moderate, marked difference, full paralysis).
II: Course of headache before and after injection:
1. Change from baseline in frequency of moderate/severe headache days (main efficacy variable). Moderate-severe headache day defined as headache lasting > 4 hours where pain becomes at least moderate in intensity. 2. Change from baseline in headache days headache day defined as headache lasting > 4 hours where pain intensity may be mild, moderate, or severe. 3. Change from baseline in frequency of migraine headache days 4. Change from baseline in frequency of acute headache pain medication intakes (all categories) 5. Change from baseline in frequency of triptan intake 6. Change from baseline in frequency of moderate/severe headache days week 1-12 after injection
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
I: The patient will also be asked about this at telphone calls from the study nurse 1-2 weeks and 8-9 weeks after injection, and at the final visit to the doctor 12 weeks after injection.
II: Data on the course of headache is recorded in the diary every day from 4 weeks before till 12 weeks after the injection. The baseline period (4 weeks) is mainly compared with the weeks 5-8 after the injections.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, and evaluation of possibility of unblinding through side effects (loss of forehead wrinkles) in a later placebo-controlled study, double blind study. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |