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

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

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.

Study Overview

• Status: Completed
• Conditions: Migraine Headaches
• Intervention / Treatment: Drug: ELS-M11; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Head Pain and Neurological Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29464
      • Coastal Carolina Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Achelios Therapeutics
• Investigators: Study Chair: Crist J. Frangakis, Ph.D., Achelios Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: February 5, 2014
• First Submitted That Met QC Criteria: February 5, 2014
• First Posted (Estimate): February 7, 2014

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: July 7, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Migraine headache; Topical treatment; Photophobia; Aura; Phonophobia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketoprofen
• Other Study ID Numbers: ACH10200