Study to Determine the Efficacy and Safety of ELS-M11 in Acute Migraine

Study Overview
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Brief Summary
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This is a Phase 1/ Phase 2, 12-week, multi-center, randomized, double-blind, cross-over, placebo-controlled study to evaluate the efficacy and safety of ELS-M11 compared to placebo in 50 male and female subjects, aged 18 to 65 years that suffer recurring moderate-severe migraine headaches (2-8 per month). This study is designed to describe the efficacy and safety of ELS-M11 as compared to placebo.

Detailed Description
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Achelios is developing ELS-M11 for topical application for the acute treatment of migraine events in patients with a history of migraine with or without aura. To be eligible for the study, patients must have a one-year documented history of migraine headache (as defined by the International Headache Society IHS), with or without aura, with 2≤8 moderate or severe migraine attacks per month in the 2 months prior to the screening visit. The total duration of the study is the completion of five migraine headaches per subject over a maximum 12 week period followed by a 3-14 day Follow-Up Period.

Official Title
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A Randomized, Double-Blind, Cross-Over, Placebo-Controlled Study to Determine the Efficacy and Safety of ELS-M11 in Acute Migraine

Conditions
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Migraine Headaches

Intervention / Treatment
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* Drug: ELS-M11
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent Males and females aged 18-65 who can read, write and understand English Subject has at least a one year documented history of migraine headache (defined by International headache Society IHS) migraine definitions, with or without aura, with 2≤8 moderate or severe migraine attacks per month in the 2 months prior to the screening visit Is stable on the current standard non-opioid rescue medication for at least 2 months prior to randomization Can distinguish migraine from tension headache (HA), with 24 hours of freedom from HA between migraine events Women of childbearing potential must be currently using or willing to use contraception (30 days prior to start of study medication and for 21 days after taking study medication) Women of non-childbearing potential include females regardless of age, with functioning ovaries and who have a current documented tubal ligation [Hatcher, 2004] bilateral oophorectomy or total hysterectomy, or post-menopausal females The subject is able and willing to perform the assessments and procedures as specified in this protocol, including the ability to learn and follow instructions for ePRO device Exclusion Criteria: Migraineurs taking opioid-based rescue medications for any indication Subject has history of mild migraine events or migraines that usually resolve spontaneously in less than 2 hours Subject has menstrual migraines Positive Drug Test Subject has basilar or hemiplegic migraines Subject has more than 15 headache-days per month Subjects with a history of facial allodynia Subject has a history of vomiting during more than 30% of migraine episodes Self confinement to bed rest for more than 50% of migraine episodes Subject was greater than 50 years old at age of migraine onset Acute coronary syndrome (i.e., myocardial infarction and unstable angina), stroke or resuscitated cardiac arrest within the past 3 months Severe congestive heart failure Systolic blood pressure (sBP) >160 mmHg or diastolic blood pressure (dBP) >100 mmHg measured in the sitting position at Visit 1 Current active renal disease Any history of pyelonephritis Evidence of active liver disease Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase >2 times the upper limit of the reference range (ULRR), or total bilirubin >1.5 times the ULRR at Visit 1 Past history of acute pancreatitis with current triglycerides 4.56 mmol/L (400 mg/dL) at Visit 1 History of malignancy within the past 3 years, other than non-melanoma skin cancer (i.e., basal or superficial squamous cell carcinoma) and treated cervical cancer in-situ Any planned major surgery to be performed during the study (e.g., coronary artery bypass surgery, abdominal aortic aneurysm repair, etc.) Current life-threatening condition Significant hypersensitivity to NSAIDs (e.g., difficulty swallowing or breathing, tachycardia, anaphylaxis, angioedema or skin reaction) Pregnancy (defined by positive urine pregnancy test) or lactation at Visit 1, or planning to become pregnant prior to completion of the study History or suspicion of alcohol or substance abuse (current or past 6 months). Participation in any clinical trial within 30 days prior to Visit 1 Subjects with a history of hypersensitivity to products containing tiaprofenic acid, suprofen, fenofibrate, oxybenzone, or octocrylene (e.g., sunscreen, perfume) Subjects with a history of photosensitivity Any clinically significant abnormality or any reason that the subject may not be able to complete the full study observational period

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ELS-M11<br>Topical 5% ELS-M11 (3 g) | Drug: ELS-M11<br>* One dose of 5% ELS-M11 over 3 bilateral applications.<br>* Other names: Topofen (ketoprofen) Gel 5%;Drug: Placebo<br>* One dose of matching placebo over 3 bilateral applications.<br>|
| Placebo Comparator: Placebo<br>A matching formulation with no active ingredient | Drug: ELS-M11<br>* One dose of 5% ELS-M11 over 3 bilateral applications.<br>* Other names: Topofen (ketoprofen) Gel 5%;Drug: Placebo<br>* One dose of matching placebo over 3 bilateral applications.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who experience pain relief 2 hours following the first application of ELS-M11 | Pain relief (as defined by a one point decrease on a 4 point pain intensity scale) in subjects experiencing a moderate to severe migraine headache, 2 hours after the initial application of ELS-M11. | 2 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who report pain relief at various time points within a 24 hour period, following the first application of ELS-M11 | Pain relief (as defined by a one point decrease on a 0-3 point pain intensity scale) in subjects experiencing a moderate to severe migraine headache over a 24 hour period following the first application of ELS-M11. | 24 hours | 
| Percentage of patients who report complete pain resolution within 24 hours following the first application of ELS-M11. | Complete resolution (intensity score of 0 on a 0-3 pain scale) of migraine pain within 24 hours, following ELS-M11 application in subjects experiencing a moderate to severe migraine headache. | 24 hours | 
| Percentage of patients who report sustained pain relief after the first application of ELS-M11 | Sustained pain relief defined as pain relief by 2 hours post study medication application with no increase in the pain intensity score up to 24 hours post medication application in moderate and severe headaches, following ELS-M11 application. | 24 hours | 
| Percentage of patients who report sustained complete pain resolution after the first application of ELS-M11. | Sustained complete pain resolution defined as pain free by 2 hours post study medication application with no change in a pain intensity score of 0 up to 24 hours post medication application in moderate and severe headaches, following ELS-M11 application. | 24 hours | 
| Time to Initial Use of Rescue Medication following the first application of ELS-M11 | Time to Initial Use of Rescue Medication following ELS-M11 application in subjects experiencing moderate to severe headaches within a 24 hour period | 24 hours | 
| Use of Rescue Medication following the first application of ELS-M11 by 24 hours | Use of Rescue Medication within 24 hours following ELS-M11 application in patients experiencing moderate to severe migraine headaches. | 24 hours | 
| Resolution of migraine-associated symptoms, following the first application of ELS-M11 | Free of migraine-associated symptoms within 24 hours after ELS-M11 application in patients experiencing moderate to severe migraine headaches. | 24 hours | 
| Percentage of patients who can resume or maintain their normal routine, following the first application of ELS-M11. | Resuming or maintaining normal routine within 24 hours after first study medication application in moderate and severe headaches. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Migraine headache, Photophobia, Phonophobia, Aura, Topical treatment