Clinical trial NCT02745392: Safety and Efficacy of ZP-Zolmitriptan Intracutaneous Microneedle Systems for the Acute Treatment of Migraine
Official title: Randomized, Double-blind, Multi-center, Parallel-group, Dose-ranging Comparison of the Safety and Efficacy of the ZP-Zolmitriptan Intracutaneous Microneedle Systems to Placebo for the Acute Treatment of Migraine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acute Migraine
Keywords: migraine
migraine headache
acute migraine
acute migraine headache
Lead sponsor: Zosano Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2016-04-20
Enrollment: 365
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Proportion of Subjects With Pain Freedom
timeFrame: 2 hours
measure: Proportion of Subjects With Freedom From Most Bothersome Pre-specified Other Symptom (Nausea, Photophobia, or Phonophobia Pre-specified by Subject)
timeFrame: 2 hours
Secondary outcomes:
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Clinical Research Advantage, Inc./Thunderbird Internal Medicine
state: Arizona
city: Carlsbad
country: United States
facility: The Research Center of Southern California
state: California
city: Huntington Beach
country: United States
facility: Allergy and Asthma Specialists Medical Group and Research Center
state: California
city: Los Angeles
country: United States
facility: Downtown LA Research Center
state: California
city: Mission Viejo
country: United States
facility: Allergy & Asthma Associates of Southern California
state: California
city: San Jose
country: United States
facility: Allergy and Asthma Associates of Santa Clara Valley Research Center
state: California
city: Santa Monica
country: United States
facility: California Medical Clinic for Headache
state: California
city: Upland
country: United States
facility: Empire Clinical Research
state: California
city: Denver
country: United States
facility: Colorado Allergy & AsthmaCenters, PC
state: Colorado
city: Stamford
country: United States
facility: Ki Health Partners
state: Connecticut
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Orange City
country: United States
facility: Medical Research Group of Central Florida
state: Florida
city: Tampa
country: United States
facility: Meridien Research
state: Florida
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Boston
country: United States
facility: Boston Clinical Trials
state: Massachusetts
city: New Bedford
country: United States
facility: Novex Medical Research
state: Massachusetts
city: North Dartmouth
country: United States
facility: Northeast Medical Research Associates, Inc.
state: Massachusetts
city: Watertown
country: United States
facility: MedVadis Research Corporation
state: Massachusetts
city: Ann Arbor
country: United States
facility: Michigan Head Pain &Neurological Institute
state: Michigan
city: Kalamazoo
country: United States
facility: Westside Family Medical Center, P.C
state: Michigan
city: Minneapolis
country: United States
facility: Clinical Research Institute, Inc.
state: Minnesota
city: Saint Louis
country: United States
facility: The Clinical Research Center, LLC
state: Missouri
city: Springfield
country: United States
facility: Clinvest/A Division of Banyan Group Inc.
state: Missouri
city: Bellevue
country: United States
facility: Nebraska Medical Research Institute
state: Nebraska
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Skillman
country: United States
facility: Princeton Center for Clinical Research
state: New Jersey
city: Greensboro
country: United States
facility: Headache Wellness Center, PC
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research LLC
state: North Carolina
city: Raleigh
country: United States
facility: North Carolina Clinical Research
state: North Carolina
city: Raleigh
country: United States
facility: PMG Research of Raleigh
state: North Carolina
city: Cincinnati
country: United States
facility: CTI Clinical Research Center
state: Ohio
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Nashville
country: United States
facility: Nashville Neurosciences Group
state: Tennessee
city: New Braunfels
country: United States
facility: Central Texas Health Research
state: Texas
city: San Antonio
country: United States
facility: Sylvana Research Associates
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center LLC
state: Virginia
Study officials:
affiliation: Zosano Pharma Corporation
name: Donald Kellerman, Pharm.D.
role: STUDY_DIRECTOR
References:
citation: Tepper SJ, Dodick DW, Schmidt PC, Kellerman DJ. Efficacy of ADAM Zolmitriptan for the Acute Treatment of Difficult-to-Treat Migraine Headaches. Headache. 2019 Apr;59(4):509-517. doi: 10.1111/head.13482. Epub 2019 Jan 30.
citation: Spierings EL, Brandes JL, Kudrow DB, Weintraub J, Schmidt PC, Kellerman DJ, Tepper SJ. Randomized, double-blind, placebo-controlled, parallel-group, multi-center study of the safety and efficacy of ADAM zolmitriptan for the acute treatment of migraine. Cephalalgia. 2018 Feb;38(2):215-224. doi: 10.1177/0333102417737765. Epub 2017 Oct 12.