A Study to Evaluate the Long-Term Safety of M207 in the Acute Treatment of Migraine (ADAM)

A Long-Term, Open-Label Study to Evaluate the Safety of M207 (Zolmitriptan Intracutaneous Microneedle System) in the Acute Treatment of Migraine

This is an open-label, twelve-month safety study. There is a screening period followed by a run-in period to record migraine activity. Qualified subjects will receive study medication for up to twelve months for the treatment of multiple migraine attacks. Using the electronic diary (eDiary) to confirm they are experiencing a qualified migraine, subjects will self-administer the patches and respond to questions in the eDiary post treatment administration.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: M207 Microneedle System

Detailed Description

This is an open-label, twelve-month safety study. There is a screening period followed by a run-in period (14 to 21 days) to determine eligibility for treatment with study medication based on daily eDiary data collection. Qualified subjects will receive study medication on Day 1 for up to twelve months for the treatment of migraine headaches. Migraines will be treated with a single dose, consisting of two patches, but subjects can treat multiple migraine attacks throughout the 12 months. Using the eDiary to confirm they are experiencing a qualified migraine, subjects will self-administer the patches and continue to respond to questions in the eDiary for 48 hours post treatment administration.

• Study Type: Interventional
• Enrollment (Actual): 342
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies
  • California
    • Los Angeles, California, United States, 90017
      • Downtown L.A. Research Center
    • Palo Alto, California, United States, 94304
      • Stanford University Medical Center
    • San Jose, California, United States, 95117
      • Allergy Asthma Associates of Santa Clara Valley Research Center
    • Santa Monica, California, United States, 90404
      • California Medical Clinic for Headache
    • Upland, California, United States, 91786
      • Empire Clinical Research
  • Colorado
    • Denver, Colorado, United States, 80230
      • Colorado Allergy Asthma Centers
  • Florida
    • Hialeah, Florida, United States, 33016
      • Harmony Medical Research Institute
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Advanced Clinical Research
  • Louisiana
    • New Orleans, Louisiana, United States, 70124
      • Delricht Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Boston Clinical Trials
    • Watertown, Massachusetts, United States, 02472
      • MedVadis Research Corporation
  • Michigan
    • Ann Arbor, Michigan, United States, 48104
      • Michigan Headache and Neurological Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55402
      • Clinical Research Institute
    • Plymouth, Minnesota, United States, 55441
      • Clinical Research Institute
  • Missouri
    • Saint Peters, Missouri, United States, 63303-3041
      • StudyMetrix Research LLC
    • Springfield, Missouri, United States, 65810
      • Clinvest Research
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • Peters Medical Research
    • Raleigh, North Carolina, United States, 27607
      • North Carolina Clinical Research
    • Raleigh, North Carolina, United States, 27609
      • Raleigh Medical Group PMG Research
  • North Dakota
    • Fargo, North Dakota, United States, 58103
      • Lillestol Research
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Primary Care Associates/Radiant Research
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Carolina Research Center
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center - Neurology Clinic
    • New Braunfels, Texas, United States, 78130
      • Central Texas Health Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

1. Women or men 18 to 75 years of age
2. Greater than 1 year history of episodic, migraine (with or without aura) with onset prior to 50 years of age.

3. Migraine history during the prior 6 months must include:

   1. at least 2 migraines per month
   2. no more than 8 migraines per month
   3. no more than 15 headache days per month
4. Women of child-bearing potential must not be pregnant, must agree to avoid pregnancy and use an acceptable double-barrier method of birth control during the trial.
5. Willing and able to treat a minimum of 2 migraines per month with study medication and consistently complete eDiary for up to 12 months.

Main Exclusion Criteria:

1. Contraindication to triptans
2. Use of selective serotonin reuptake inhibitors (drugs like Prozac®) or serotonin or norepinephrine reuptake inhibitors (drugs like Effexor®) or anti-coagulants (drugs like Coumadin®)
3. Known allergy or sensitivity to zolmitriptan or its derivatives or formulations
4. Known allergy or sensitivity to adhesives and/or titanium
5. Women who are pregnant, breast-feeding or plan a pregnancy during this study

6. Three or more of the following cardiovascular risk factors:

   • Current tobacco use
   • Hypertension or receiving anti-hypertensive medication for hypertension
   • Hyperlipidemia or on prescribed anti-cholesterol treatment
   • Family history of premature coronary artery disease
   • Diabetes mellitus
7. History or current abuse or dependence on alcohol or drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: M207 Microneedle System 3.8 mg; M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches)	Drug: M207 Microneedle System; M207 Microneedle System 3.8 mg; Other Names: ZP-Zolmitriptan Intracutaneous Microneedle System; ADAM-Zolmitriptan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Any Treatment-emergent Adverse Events (TEAE) Over 12 Months	Number and % of subjects in safety population with any treatment-emergent adverse event(s) during the study. TEAE is defined as any new adverse event (AE) that started after first patch application. This was an open-label study with no control group. No statistical analyses were performed. Application site skin reactions including erythema, swelling, haemorrhage, bruise, pain, and pruritus were collected systematically via subject e-diary and/or investigator skin assessment at study visits. All other AEs were spontaneously reported by subject or observed upon examination.	0 to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Migraine Attacks for Which Pain Freedom Was Achieved at 2 Hours Post-dose	Percentage of migraine attacks for which pain freedom defined as a pain level of 'None' (Grade 0 on pain severity scale where 0: None, 1: Mild, 2: Moderate, 3: Severe, and lower values represent a better outcome) was achieved at 2 hours post-dose without the use of rescue medication. This was an open-label study with no control group. No statistical analyses were performed.	2 hours for each Migraine, up to 12 months for each subject
Percentage of Migraine Attacks for Which Most Bothersome Symptom Freedom Was Achieved at 2 Hours Post-dose	Percentage of migraine attacks for which freedom from most bothersome symptom other than pain defined as an absence of the most bothersome symptom was achieved at 2 hours post-dose without the use of rescue medication. This was an open-label study with no control group. No statistical analyses were performed.	2 hours for each Migraine, up to 12 months for each subject
Percentage of Migraine Attacks for Which Pain Relief Was Achieved at 2 Hours Post-dose	Percentage of migraine attacks for which pain relief defined as an improvement of pain severity (1) to mild (Grade 1) or none (Grade 0) from moderate (Grade 2) or severe (Grade 3) at baseline, or (2) an improvement of pain severity to none (Grade 0) from mild (Grade 1) at baseline, without rescue medication was achieved. Pain severity scale has grades: 0: None, 1: Mild, 2: Moderate, 3: Severe, where lower values represent a better outcome. This was an open-label study with no control group. No statistical analyses were performed.	2 hours for each Migraine, up to 12 months for each subject
Percentage of Migraine Attacks for Which Nausea Freedom Was Achieved at 2 Hours Post-dose	Percentage of subjects for which nausea freedom defined as absence of nausea and/or vomiting without the use of rescue medication was achieved at 2 hours post-dose. This was an open-label study with no control group. No statistical analyses were performed.	2 hours for each Migraine, up to 12 months for each subject
Percentage of Migraine Attacks for Which Photophobia Freedom Was Achieved at 2 Hours Post-dose	Percentage of migraine attacks for which photophobia freedom defined as an absence of photophobia without the use of rescue medication was achieved at 2 hours post-dose. This was an open-label study with no control group. No statistical analyses were performed.	2 hours for each Migraine, up to 12 months for each subject
Percentage of Migraine Attacks for Which Phonophobia Freedom Was Achieved at 2 Hours Post-dose	Percentage of migraine attacks for which phonophobia freedom defined as an absence of phonophobia without the use of rescue medication was achieved at 2 hours post-dose. This was an open-label study with no control group. No statistical analyses were performed.	2 hours for each Migraine, up to 12 months for each subject

Collaborators and Investigators

• Sponsor: Zosano Pharma Corporation
• Investigators: Study Director: Don Kellerman, Pharm.D., Zosano Pharma Corporation

Publications and helpful links

General Publications

• Nahas SJ, Hindiyeh N, Friedman DI, Elbuluk N, Kellerman DJ, Foreman PK, Schmidt P. Long term safety, tolerability, and efficacy of intracutaneous zolmitriptan (M207) in the acute treatment of migraine. J Headache Pain. 2021 May 17;22(1):37. doi: 10.1186/s10194-021-01249-z.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2017
• Primary Completion (Actual): May 17, 2019
• Study Completion (Actual): May 17, 2019

Study Registration Dates

• First Submitted: September 5, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (Actual): September 13, 2017

Study Record Updates

• Last Update Posted (Actual): August 19, 2020
• Last Update Submitted That Met QC Criteria: August 7, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: migraine; migraine headache; acute migraine; acute migraine headache
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Serotonin Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Protein Synthesis Inhibitors; Oxazolidinones; Zolmitriptan
• Other Study ID Numbers: CP-2017-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No