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

Acute Migraine Clinical Trial

— Zotrip  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02745392
• Other study ID #: CP-2016-001
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: April 14, 2016
• Last updated: February 13, 2018
• Start date: June 2016
• Est. completion date: January 2017

Study information

• Verified date: February 2018
• Source: Zosano Pharma Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 365
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Migraine
• Migraine Disorders

Intervention

Drug:
• ZP-Zolmitriptan
ZP-Zolmitriptan single administration delivered via intracutaneous microneedle patch delivery system
• Placebo
Placebo patch(es) to match ZP-Zolmitriptan single administration delivered via intracutaneous microneedle patch delivery system (one or two patches)

Locations

Country	Name	City	State
United States	Michigan Head Pain &Neurological Institute	Ann Arbor	Michigan
United States	Nebraska Medical Research Institute	Bellevue	Nebraska
United States	Boston Clinical Trials	Boston	Massachusetts
United States	The Research Center of Southern California	Carlsbad	California
United States	Charlottesville Medical Research Center LLC	Charlottesville	Virginia
United States	CTI Clinical Research Center	Cincinnati	Ohio
United States	Avail Clinical Research, LLC	DeLand	Florida
United States	Colorado Allergy & AsthmaCenters, PC	Denver	Colorado
United States	Clinical Research Advantage, Inc./Thunderbird Internal Medicine	Glendale	Arizona
United States	Headache Wellness Center, PC	Greensboro	North Carolina
United States	Peters Medical Research LLC	High Point	North Carolina
United States	Allergy and Asthma Specialists Medical Group and Research Center	Huntington Beach	California
United States	Westside Family Medical Center, P.C	Kalamazoo	Michigan
United States	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	Downtown LA Research Center	Los Angeles	California
United States	Clinical Research Institute, Inc.	Minneapolis	Minnesota
United States	Allergy & Asthma Associates of Southern California	Mission Viejo	California
United States	Coastal Carolina Research Center	Mount Pleasant	South Carolina
United States	Nashville Neurosciences Group	Nashville	Tennessee
United States	Novex Medical Research	New Bedford	Massachusetts
United States	Central Texas Health Research	New Braunfels	Texas
United States	Northeast Medical Research Associates, Inc.	North Dartmouth	Massachusetts
United States	Medical Research Group of Central Florida	Orange City	Florida
United States	North Carolina Clinical Research	Raleigh	North Carolina
United States	PMG Research of Raleigh	Raleigh	North Carolina
United States	The Clinical Research Center, LLC	Saint Louis	Missouri
United States	Sylvana Research Associates	San Antonio	Texas
United States	Allergy and Asthma Associates of Santa Clara Valley Research Center	San Jose	California
United States	California Medical Clinic for Headache	Santa Monica	California
United States	Princeton Center for Clinical Research	Skillman	New Jersey
United States	Clinvest/A Division of Banyan Group Inc.	Springfield	Missouri
United States	Ki Health Partners	Stamford	Connecticut
United States	Clinical Research Atlanta	Stockbridge	Georgia
United States	Meridien Research	Tampa	Florida
United States	Empire Clinical Research	Upland	California
United States	MedVadis Research Corporation	Watertown	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Zosano Pharma Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of Subjects With Pain Freedom	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.	2 hours
Primary	Proportion of Subjects With Freedom From Most Bothersome Pre-specified Other Symptom (Nausea, Photophobia, or Phonophobia Pre-specified by Subject)	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.	2 hours