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Safety and Efficacy of ZP-Zolmitriptan Intracutaneous Microneedle Systems for the Acute Treatment of Migraine

Phase 2
Completed
Conditions
Acute Migraine
Interventions
Drug: ZP-Zolmitriptan
Drug: Placebo
Registration Number
NCT02745392
Lead Sponsor
Zosano Pharma Corporation
Brief Summary

This is a randomized, double-blind, multi-center, parallel-group study designed to compare the safety and efficacy of a range of doses of ZP-Zolmitriptan intracutaneous microneedle systems to placebo.

Detailed Description

This is a randomized, double-blind, multi-center, parallel group study designed to compare the safety and efficacy of a range of doses of ZP-Zolmitriptan intracutaneous microneedle systems to placebo. Subjects who have consented and meet the entry criteria will be randomized to one of four blinded treatment groups. There will be a screening period of up to 1 week, followed by a run-in period to record migraine activity. The run-in period is to determine eligibility for randomization, and is planned to be 4 weeks in duration but may be extended up to an additional 4 weeks to accommodate scheduling. Qualified subjects will randomize to the double-blind treatment period at Day 0 and will have up to 8 weeks to confirm and treat a qualifying migraine. Using the eDiary to confirm they are experiencing a qualified migraine, subjects will self-administer the patch or patches and continue to respond to questions in the eDiary for 48 hours post treatment administration.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
365
Inclusion Criteria
  • Greater than 1 year history of episodic, acute migraine (with or without aura) with onset prior to 50 years of age. Diagnosis must comply with International Headache Society (IHS) diagnostic criteria. Diagnostic criteria must include a history of at least five attacks not attributed to any other disorder that include all of the following criteria:

    1. Headache attacks lasting 4-72 hours (untreated or unsuccessfully treated)
    2. Headache has at least two of the following characteristics:

    (i) unilateral location (ii) pulsating quality (iii) moderate or severe pain intensity (iv) aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) c) During headache at least one of the following: (i) nausea and/or vomiting (ii) both photophobia and phonophobia

  • Migraine history during the 6-month period prior to the run-in period must include: 2-8 migraines per month and no more than 10 headache days per month

  • Women of child-bearing potential must not be pregnant, must agree to avoid pregnancy during the trial, and must use an acceptable methods of birth control for the duration of the trial.

  • No significant ECG findings, defined by:

    1. ischemic changes
    2. Q-waves in at least two contiguous leads,
    3. clinically significant intra-ventricular conduction abnormalities (left bundle branch block or Wolf-Parkinson-White syndrome), or
    4. clinically significant arrhythmias (e.g., current atrial fibrillation)
  • Able to understand the operation of the electronic diary and is able to apply the demo study drug patch.

Exclusion Criteria
  • Contraindication to triptans

  • Use of any prohibited concomitant medications within 10 days of the Run-in Period

  • History of hemiplegic or basilar migraine

  • Participation in another investigational trial during the 30 days prior to the Run-in Period or during this study

  • Previous participation in a clinical trial of ZP-Zolmitriptan

  • Diagnosis of cancer (other than non-invasive skin cancer) within the 5 years prior to the Run-in Period

  • History of unstable psychiatric illness requiring medication or hospitalization in the 12 months prior to the Run-in Period

  • Subjects who have known allergy or sensitivity to zolmitriptan or its derivatives or formulations

  • Subjects who have known allergy or sensitivity to adhesives

  • Planned participation in activities which cause inflammation, irritation, sunburn, lesions, or tattoos at the intended application site from two weeks prior to screening through the last day of study participation

  • Use of opiate analgesics or barbiturates more frequently than one day/week

  • Women who are pregnant, breast-feeding or plan a pregnancy during this study

  • Clinically significant liver disease

  • Clinically significant kidney disease

  • History of coronary artery disease (CAD), coronary vasospasm (including Prinzmetal's angina), aortic aneurysm, peripheral vascular disease or other ischemic diseases (e.g., ischemic bowel syndrome or Raynaud's syndrome)

  • Three or more of the following CAD risk factors:

    • Current tobacco use
    • Hypertension or receiving anti-hypertensive medication for treatment of hypertension
    • Hyperlipidemia or on prescribed anti-cholesterol treatment
    • Family history of premature coronary artery disease (< 55 years of age in male first degree relatives or < 65 years of age in female first degree relatives)
    • Diabetes mellitus
  • History of cerebral vascular accident, transient ischemic attacks, or seizures

  • Hospitalization within the 30 days prior to the Run-in Period

  • Any other household member currently participating in a ZP-Zolmitriptan study or relatives of site staff

  • Any reason to believe that compliance with the study requirements and completion of evaluations required for this study will not be possible

  • History or current abuse or dependence on alcohol or drugs that would interfere with adherence to study requirements

  • Any clinically relevant abnormal findings in the physical exam, vital signs or laboratory tests that, in the opinion of the Investigator, may put the subject at risk

To be eligible for Treatment, subjects must continue to meet all eligibility criteria and the following criteria observed during the Run-in Period:

  1. An average of at least two qualifying migraines per 28-day period
  2. No more than 10 headache days in the last 28 days prior to randomization
  3. Demonstrated ability to properly use the eDiary and apply the demo study drug patch
  4. Confirmation of continuing good general health, or stable non-serious disease that in the opinion of the Investigator will not place the subject at risk.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ZP-Zolmitriptan 3.8 mgZP-ZolmitriptanZP-Zolmitriptan 3.8 mg (1.9 mg x 2 patches) single administration
ZP-Zolmitriptan 1 mgZP-ZolmitriptanZP-Zolmitriptan 1 mg patch single administration
ZP-Zolmitriptan 1.9 mgZP-ZolmitriptanZP-Zolmitriptan 1.9 mg patch single administration
PlaceboPlaceboPlacebo (either single or double patch) single administration
Primary Outcome Measures
NameTimeMethod
Proportion of Subjects With Freedom From Most Bothersome Pre-specified Other Symptom (Nausea, Photophobia, or Phonophobia Pre-specified by Subject)2 hours

The proportion of subjects with freedom from the subject's pre-specified most bothersome symptom at 2 hours is one of two parts of the co-primary efficacy endpoint. This endpoint will be evaluated separately but both endpoints have to be met statistically for the study to be considered a success.

Proportion of Subjects With Pain Freedom2 hours

Pain Freedom at 2 hours post study drug administration is one of the co-primary endpoints. Subjects were queried via their eDiary about their level of migraine pain (none, mild, moderate, or severe) at various intervals post-dose. Subjects who answered none at 2 hours post study drug were considered pain free at 2 hours.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (36)

Dartmouth-Hitchcock Medical Center

🇺🇸

Lebanon, New Hampshire, United States

Novex Medical Research

🇺🇸

New Bedford, Massachusetts, United States

Clinvest/A Division of Banyan Group Inc.

🇺🇸

Springfield, Missouri, United States

The Research Center of Southern California

🇺🇸

Carlsbad, California, United States

Coastal Carolina Research Center

🇺🇸

Mount Pleasant, South Carolina, United States

California Medical Clinic for Headache

🇺🇸

Santa Monica, California, United States

Ki Health Partners

🇺🇸

Stamford, Connecticut, United States

Boston Clinical Trials

🇺🇸

Boston, Massachusetts, United States

Allergy and Asthma Specialists Medical Group and Research Center

🇺🇸

Huntington Beach, California, United States

Avail Clinical Research, LLC

🇺🇸

DeLand, Florida, United States

Clinical Research Atlanta

🇺🇸

Stockbridge, Georgia, United States

Headache Wellness Center, PC

🇺🇸

Greensboro, North Carolina, United States

Meridien Research

🇺🇸

Tampa, Florida, United States

Michigan Head Pain &Neurological Institute

🇺🇸

Ann Arbor, Michigan, United States

The Clinical Research Center, LLC

🇺🇸

Saint Louis, Missouri, United States

Westside Family Medical Center, P.C

🇺🇸

Kalamazoo, Michigan, United States

Downtown LA Research Center

🇺🇸

Los Angeles, California, United States

Clinical Research Advantage, Inc./Thunderbird Internal Medicine

🇺🇸

Glendale, Arizona, United States

Allergy and Asthma Associates of Santa Clara Valley Research Center

🇺🇸

San Jose, California, United States

Empire Clinical Research

🇺🇸

Upland, California, United States

MedVadis Research Corporation

🇺🇸

Watertown, Massachusetts, United States

North Carolina Clinical Research

🇺🇸

Raleigh, North Carolina, United States

Allergy & Asthma Associates of Southern California

🇺🇸

Mission Viejo, California, United States

Nebraska Medical Research Institute

🇺🇸

Bellevue, Nebraska, United States

Central Texas Health Research

🇺🇸

New Braunfels, Texas, United States

Northeast Medical Research Associates, Inc.

🇺🇸

North Dartmouth, Massachusetts, United States

Peters Medical Research LLC

🇺🇸

High Point, North Carolina, United States

Colorado Allergy & AsthmaCenters, PC

🇺🇸

Denver, Colorado, United States

Clinical Research Institute, Inc.

🇺🇸

Minneapolis, Minnesota, United States

CTI Clinical Research Center

🇺🇸

Cincinnati, Ohio, United States

Nashville Neurosciences Group

🇺🇸

Nashville, Tennessee, United States

Sylvana Research Associates

🇺🇸

San Antonio, Texas, United States

Medical Research Group of Central Florida

🇺🇸

Orange City, Florida, United States

Princeton Center for Clinical Research

🇺🇸

Skillman, New Jersey, United States

Charlottesville Medical Research Center LLC

🇺🇸

Charlottesville, Virginia, United States

PMG Research of Raleigh

🇺🇸

Raleigh, North Carolina, United States

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