A Proof of Concept Study of the Efficacy and Safety of Oral LAT8881 in Acute Migraine

Study Overview
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Brief Summary
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This is a randomised, placebo controlled, double blind, crossover proof of concept study to investigate the efficacy and safety of oral LAT8881 in acute migraine, with or without aura.

Detailed Description
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Subjects enrolled in the study will be randomised to receive investigational medicinal product (LAT8881 60 mg or placebo), to be taken at the onset (within one hour from the onset of pain) of a migraine headache of moderate to severe intensity [Numeric rating scale greater than 4]. Rescue medication should not be taken until at least 2 hours post dose. Subjects will be given a single dose of either active or placebo, to treat one migraine headache. After treatment of one migraine headache (or a maximum 28 days) the subject will return to the clinic for re-evaluation and crossover to the second treatment. After treatment of one migraine headache in the second treatment period or a maximum of 28 days from commencement of the second treatment period, the subject will return to the clinic for re-evaluation. An End of study visit (telephone) will occur 7 days after the end of the second treatment period.

Official Title
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A Proof of Concept Study of the Efficacy and Safety of Oral LAT8881 in Acute Migraine

Conditions
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Acute Migraine

Intervention / Treatment
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* Drug: LAT8881
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged 18 to 75 years at the time of consent Diagnosis of episodic migraine headache at least 12 months ago with or without aura as defined in International Classification of Headache-3 Onset of migraine headache before age 50 Medical history of 2 - 8 migraine headache attacks per month for the previous 12 months; ≥ 75% of attacks progress to moderate or severe pain within 2 hours (ie, rapidly-escalating) Minimum 48 hours on average between migraine headache attacks Acute headache medication on ≤ 14 days/month in the 3 months prior to screening Willing and able to comply with all study procedures including completion of a headache diary and a migraine diary on the day of a migraine headache Exclusion Criteria: Unable to distinguish migraine from other primary headache conditions Average of 15 or more headache (migraine or nonmigraine) days per month or history of more than 25% of headaches occurring at time of wakening (wake up headaches) History of aura lasting more than 60 minutes History of vomiting within 2 hours of onset of a migraine headache in more than 25% of migraine headaches Medication overuse headache, defined as: use of opioids, triptans or ergot alkaloids or any combination of these medications for treatment of headaches 10 or more days per month during the 90 days prior to screening OR Non-steroidal anti-inflammatory drugs (NSAIDs) or simple analgesics for treatment of headaches on more than 14 days per month during the 90 days prior to screening Recent (3 years) history of frequent or chronic hemiplegic/ basilar migraine, tension headache, retinal migraine, ophthalmoplegic migraine as per ICHD classification, or treatment resistant atypical migraine Hospital admission for status intractable migraine or medication overuse headache within 6 months of screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomised assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Subjects will be given two 30 mg capsules of the investigational medicinal product (LAT8881), and instructed to take both capsules within the first hour of the onset of a migraine of moderate to severe intensity. | Drug: LAT8881<br>* Two 30 mg capsules of LAT8881<br>|
| Placebo Comparator: Placebo<br>Subjects will be given two capsules of placebo, and instructed to take both capsules within the first hour of the onset of a migraine of moderate to severe intensity. | Drug: Placebo<br>* Two capsules of placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Migraine Headache Pain Score From Time of Dosing (0 Minutes) | Change in migraine headache pain score, using an 11-point numeric rating scale (NRS), (0 = none, 10 = worst imaginable), Pain is recorded in a subject diary and should reflect the subject's pain at the time of recording. A reduction in NRS score indicates a reduction in pain intensity. | 0 minutes, 30 minutes, 60 minutes, 90 minutes, 2 hours, 4 hours, 8 hours and 24 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Migraine-associated Symptoms of Nausea, Photophobia and Phonophobia From Time of Dosing (0 Minutes) | Symptoms are assessed on an 11- point Likert scale (0 = no symptoms, 10 = severe symptoms). A larger negative number represents a greater reduction in symptom intensity | 0 minutes, 30 minutes, 60 minutes, 90 minutes, 2 hours, 4 hours, 8 hours and 24 hours post dose | 
| Change in Each Subject's Most Troublesome Symptom From Time of Dosing (0 Minutes) | Symptoms are assessed on an 11- point Likert scale (0 = no symptoms, 10 = severe symptoms). A larger negative number represents a greater reduction in symptom intensity. | 0 minutes, 30 minutes, 60 minutes, 90 minutes, 2 hours, 4 hours, 8 hours and 24 hours post dose | 
| The Percentage of Subjects Achieving no Headache Pain | Defined as having no migraine headache pain | 30 minutes, 60 minutes, 90 minutes, 2 hours, 4 hours, 8 hours post-dose |