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CompletedNCT03282227ADAMUpdated Aug 19, 2020Results posted

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

A Phase 3 interventional study of M207 Microneedle System in Migraine, sponsored by Zosano Pharma Corporation. Completed at 31 sites in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2020-08-19.

Sponsored by Zosano Pharma Corporation · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
342
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Migraine

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Keywords

  • migraine
  • migraine headache
  • acute migraine
  • acute migraine headache
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

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
04

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
342 participants (actual)

Study arms

  • Experimental
    M207 Microneedle System 3.8 mg

    M207 Microneedle System 3.8 mg (1.9 mg/patch x 2 patches)

    Drug: M207 Microneedle System

Interventions

  • DrugM207 Microneedle System

    M207 Microneedle System 3.8 mg

    Also known as: ZP-Zolmitriptan Intracutaneous Microneedle System, ADAM-Zolmitriptan

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: 0 to 12 months

Secondary outcomes

  1. 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.

    Time frame: 2 hours for each Migraine, up to 12 months for each subject

  2. 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.

    Time frame: 2 hours for each Migraine, up to 12 months for each subject

  3. 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.

    Time frame: 2 hours for each Migraine, up to 12 months for each subject

  4. 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.

    Time frame: 2 hours for each Migraine, up to 12 months for each subject

  5. 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.

    Time frame: 2 hours for each Migraine, up to 12 months for each subject

  6. 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.

    Time frame: 2 hours for each Migraine, up to 12 months for each subject

06

Results

Posted Aug 19, 2020

Participant flow

Participant flow — Overall Study
MilestoneM207 Microneedle System 3.8 mg
Started342
Completed at least 6 months257
Completed127
Not completed215
Withdrew: Exposure goals achieved60
Withdrew: Non-compliance w/ protocol requirements79
Withdrew: Adverse event15
Withdrew: Lost to follow-up21
Withdrew: Withdrawal by subject20
Withdrew: Lack of efficacy12
Withdrew: Sponsor decision3
Withdrew: Physician decision2
Withdrew: Pregnancy2
Withdrew: Other1

Outcome measures

PrimaryNumber 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.

Time frame:
0 to 12 months
Reported as:
Count of participants · Participants
Number of Subjects With Any Treatment-emergent Adverse Events (TEAE) Over 12 Months
ParticipantsM207 Microneedle System 3.8 mg
Number of Subjects With Any Treatment-emergent Adverse Events (TEAE) Over 12 Months323
SecondaryPercentage 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.

Time frame:
2 hours for each Migraine, up to 12 months for each subject
Reported as:
Count of units · Qualifying migraines with 2 hour data
Percentage of Migraine Attacks for Which Pain Freedom Was Achieved at 2 Hours Post-dose
Qualifying migraines with 2 hour dataM207 Microneedle System 3.8 mg
Percentage of Migraine Attacks for Which Pain Freedom Was Achieved at 2 Hours Post-dose2477
SecondaryPercentage 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.

Time frame:
2 hours for each Migraine, up to 12 months for each subject
Reported as:
Count of units · Qualifying migraines with 2 hr data
Percentage of Migraine Attacks for Which Most Bothersome Symptom Freedom Was Achieved at 2 Hours Post-dose
Qualifying migraines with 2 hr dataM207 Microneedle System 3.8 mg
Percentage of Migraine Attacks for Which Most Bothersome Symptom Freedom Was Achieved at 2 Hours Post-dose3315
SecondaryPercentage 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.

Time frame:
2 hours for each Migraine, up to 12 months for each subject
Reported as:
Count of units · Qualifying migraines with 2 hr data
Percentage of Migraine Attacks for Which Pain Relief Was Achieved at 2 Hours Post-dose
Qualifying migraines with 2 hr dataM207 Microneedle System 3.8 mg
Percentage of Migraine Attacks for Which Pain Relief Was Achieved at 2 Hours Post-dose4552
SecondaryPercentage 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.

Time frame:
2 hours for each Migraine, up to 12 months for each subject
Reported as:
Count of units · Qualifying migraines with 2 hr data
Percentage of Migraine Attacks for Which Nausea Freedom Was Achieved at 2 Hours Post-dose
Qualifying migraines with 2 hr dataM207 Microneedle System 3.8 mg
Percentage of Migraine Attacks for Which Nausea Freedom Was Achieved at 2 Hours Post-dose4628
SecondaryPercentage 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.

Time frame:
2 hours for each Migraine, up to 12 months for each subject
Reported as:
Count of units · Qualifying migraines with 2 hour data
Percentage of Migraine Attacks for Which Photophobia Freedom Was Achieved at 2 Hours Post-dose
Qualifying migraines with 2 hour dataM207 Microneedle System 3.8 mg
Percentage of Migraine Attacks for Which Photophobia Freedom Was Achieved at 2 Hours Post-dose3410
SecondaryPercentage 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.

Time frame:
2 hours for each Migraine, up to 12 months for each subject
Reported as:
Count of units · Qualifying migraines with 2 hour data
Percentage of Migraine Attacks for Which Phonophobia Freedom Was Achieved at 2 Hours Post-dose
Qualifying migraines with 2 hour dataM207 Microneedle System 3.8 mg
Percentage of Migraine Attacks for Which Phonophobia Freedom Was Achieved at 2 Hours Post-dose3563

Adverse events

Collected over 0-12 months. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
M207 Microneedle System 3.8 mg0/335 (0%)5/335 (1.5%)323/335 (96.4%)
Most frequent serious events
Most frequent serious events
EventM207 Microneedle System 3.8 mg
HypokalaemiaMetabolism and nutrition disorders1/335
Foetal disorderCongenital, familial and genetic disorders1/335
Procedural painNervous system disorders1/335
Breast cancer stage IIReproductive system and breast disorders1/335
PneumoniaInfections and infestations1/335
AsthmaRespiratory, thoracic and mediastinal disorders1/335
HypoxiaRespiratory, thoracic and mediastinal disorders1/335
Most frequent other events
Showing 10 of 12
Most frequent other events
EventM207 Microneedle System 3.8 mg
Application site erythemaSkin and subcutaneous tissue disorders316/335
Application site swellingSkin and subcutaneous tissue disorders296/335
Application site haemorrhageSkin and subcutaneous tissue disorders225/335
Application site bruiseSkin and subcutaneous tissue disorders194/335
Application site painSkin and subcutaneous tissue disorders81/335
Application site discolourationSkin and subcutaneous tissue disorders53/335
Application site pruritusSkin and subcutaneous tissue disorders52/335
Upper respiratory tract infectionInfections and infestations28/335
SinusitisInfections and infestations13/335
NauseaGastrointestinal disorders9/335

Baseline characteristics

Safety population included 335 subjects (98.0%) who received any amount of study drug (applied at least 1 patch).

Age, Continuous
Age, Continuous(years)M207 Microneedle System 3.8 mg
Mean42.9 ± 12.07
Sex: Female, Male
Sex: Female, Male(Participants)M207 Microneedle System 3.8 mg
Female297
Male38
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)M207 Microneedle System 3.8 mg
Hispanic or Latino60
Not Hispanic or Latino275
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)M207 Microneedle System 3.8 mg
American Indian or Alaska Native0
Asian7
Native Hawaiian or Other Pacific Islander1
Black or African American55
White265
More than one race4
Unknown or Not Reported3
Height
Height(cm)M207 Microneedle System 3.8 mg
Mean165.20 ± 8.602
Weight
Weight(kg)M207 Microneedle System 3.8 mg
Mean79.76 ± 20.847
BMI
BMI(kg/m^2)M207 Microneedle System 3.8 mg
Mean29.19 ± 7.185
07

Study locations

31 sites
  • Achieve Clinical Research
    Birmingham, Alabama 35216, United States
  • Elite Clinical Studies
    Phoenix, Arizona 85018, United States
  • Downtown L.A. Research Center
    Los Angeles, California 90017, United States
  • Stanford University Medical Center
    Palo Alto, California 94304, United States
  • Allergy Asthma Associates of Santa Clara Valley Research Center
    San Jose, California 95117, United States
  • California Medical Clinic for Headache
    Santa Monica, California 90404, United States
  • Empire Clinical Research
    Upland, California 91786, United States
  • Colorado Allergy Asthma Centers
    Denver, Colorado 80230, United States
  • Harmony Medical Research Institute
    Hialeah, Florida 33016, United States
  • Advanced Clinical Research
    Meridian, Idaho 83642, United States
  • DelRicht Research
    New Orleans, Louisiana 70124, United States
  • Boston Clinical Trials
    Boston, Massachusetts 02131, United States
  • MedVadis Research Corporation
    Watertown, Massachusetts 02472, United States
  • Michigan Headache and Neurological Institute
    Ann Arbor, Michigan 48104, United States
  • Clinical Research Institute
    Minneapolis, Minnesota 55402, United States
  • Clinical Research Institute
    Plymouth, Minnesota 55441, United States
  • StudyMetrix Research LLC
    Saint Peters, Missouri 63303-3041, United States
  • Clinvest Research
    Springfield, Missouri 65810, United States
  • Dartmouth-Hitchcock Medical Center
    Lebanon, New Hampshire 03756, United States
  • Albuquerque Clinical Trials
    Albuquerque, New Mexico 87102, United States
  • Rochester Clinical Research
    Rochester, New York 14609, United States
  • Peters Medical Research
    High Point, North Carolina 27262, United States
  • North Carolina Clinical Research
    Raleigh, North Carolina 27607, United States
  • Raleigh Medical Group PMG Research
    Raleigh, North Carolina 27609, United States
  • Lillestol Research
    Fargo, North Dakota 58103, United States
  • Thomas Jefferson University
    Philadelphia, Pennsylvania 19107, United States
  • Primary Care Associates/Radiant Research
    Anderson, South Carolina 29621, United States
  • Coastal Carolina Research Center
    Mount Pleasant, South Carolina 29464, United States
  • FutureSearch Trials of Neurology
    Austin, Texas 78731, United States
  • University of Texas Southwestern Medical Center - Neurology Clinic
    Dallas, Texas 75390, United States
  • Central Texas Health Research
    New Braunfels, Texas 78130, United States
08

References and documents

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. PubMed 34001002 ↗

Study documents

  • Statistical analysis plan · Nov 30, 2018
  • Study protocol · Apr 6, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03282227
Lead sponsor
Zosano Pharma Corporation
Responsible party
Sponsor
First posted
Sep 13, 2017
Start date
Nov 7, 2017
Primary completion
May 17, 2019
Completion
May 17, 2019
Results posted
Aug 19, 2020
Last update
Aug 19, 2020

Study contacts

Don Kellerman, Pharm.D.
study director · Zosano Pharma Corporation

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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