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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066635 |
E.1.2 | Term | Acute migraine |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052787 |
E.1.2 | Term | Migraine without aura |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10027603 |
E.1.2 | Term | Migraine headaches |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027599 |
E.1.2 | Term | Migraine |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10027607 |
E.1.2 | Term | Migraine with aura |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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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 the efficacy at 2 hours of lasmiditan 50 mg, of lasmiditan 100 mg and of lasmiditan 200 mg compared to placebo on migraine headache pain and the Most Bothersome Symptom (MBS), as identified by the individual from the associated symptoms of nausea, phonophobia and photophobia. |
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E.2.2 | Secondary objectives of the trial |
To explore the time course and effect of lasmiditan 50 mg, of lasmiditan 100 mg and of lasmiditan 200 mg on relief of pain and on the MBS.
Additional Objectives
To explore the effect and time course of a second dose of lasmiditan 50 mg, of lasmiditan 100 mg and of lasmiditan 200 mg compared to placebo on relief of pain and MBS when used for rescue and for recurrence of migraine. To explore resource utilization during the study compared to pre-study in terms of cardiovascular events and in terms of migraine episodes.
Safety objectives
To explore the safety and tolerability of lasmiditan 50 mg, of lasmiditan 100 mg and of lasmiditan 200 mg, as the first dose and as a second dose, in terms of adverse events (AEs), physical examinations, vital signs, clinical laboratory evaluations, and 12-lead electrocardiograms (ECGs). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects entered into this trial must meet the following criteria:
1. Able and willing to give written informed consent
2. Patients with migraine with or without aura fulfilling the IHS diagnostic criteria 1.1 and 1.2.1 (ICHD-2004).
3. History of disabling migraine for at least 1 year.
4. MIDAS score ≥11.
5. Migraine onset before the age of 50 years.
6. History of 3 – 8 migraine attacks per month (< 15 headache days per month).
7. Male or female, aged 18 years or above.
8. Females of child-bearing potential must be using or willing to use a highly effective form of contraception (e.g. combined oral contraceptive, IUD, abstinence, or vasectomized partner).
9. Able and willing to complete an electronic diary to record details of the migraine attack treated with study drug. |
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E.4 | Principal exclusion criteria |
Subjects will be excluded from this trial if they meet any of the following criteria:
1. Any medical condition or clinical laboratory test which in the judgment of the Investigator makes the subject unsuitable for the study.
2. Pregnant or breast-feeding women.
3. Women of child-bearing potential not using or not willing to use highly effective contraception.
4. Known hypersensitivity to lasmiditan, or to any excipient of lasmiditan oral tablets, or any sensitivity to a ditan.
5. History or evidence of haemorrhagic stroke, epilepsy or any other condition placing the subject at increased risk of seizures.
6. History of recurrent dizziness and/or vertigo including BPPV, Meniere’s disease, vestibular migraine, and other vestibular disorders.
7. History of diabetes mellitus with complications (diabetic retinopathy, nephropathy or neuropathy).
8. History within the previous three years or current evidence of abuse of any drug, prescription or illicit, or alcohol.
9. History of orthostatic hypotension with syncope.
10. Significant renal or hepatic impairment.
11. Subject is at imminent risk of suicide (positive response to question 4 or 5 on the C-SSRS) or had a suicide attempt within six months prior to the screening visit.
12. Previous participation in this clinical trial.
13. Participation in any clinical trial of an experimental drug or device in the previous 30 days.
14. Known Hepatitis B or C or HIV infection.
15. History, within past 12 months, of chronic migraine or other forms of primary or secondary chronic headache disorder (e.g. hemicranias continua, medication overuse headache) where headache frequency is ≥15 headache days per month.
16. Use of more than 3 doses per month of either opiates or barbiturates.
17. Initiation of or a change in concomitant medication to reduce the frequency of migraine episodes within three (3) months prior to Screening/Visit 1.
18. Subjects who are employees of the sponsor.
19. Relatives of, or staff directly reporting to, the Investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of subjects headache pain free at 2 hours post dose (defined as moderate or severe headache pain becoming none)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
The proportion of subjects who are MBS free at 2 hours post dose (defined as the associated symptom present and identified as MBS prior to dosing being absent at 2 hours). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Germany |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |