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

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.

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