Safety and Tolerability of POD-DHE (INP104) in Migraine (STOP 301)

Open-label Study of Safety and Tolerability of Chronic Intermittent Usage for 24 or 52 Weeks of Intranasal Dihydroergotamine Mesylate (DHE) Administered Using the I123 Precision Olfactory Delivery (POD®) Device [INP104, POD-DHE] in Patients With Migraine Headache

This study consists of a 4-week screening period, a 24-week treatment period for all participants, followed by a 28-week treatment period extension (to 52 weeks in total) for a subset of at least 60 and up to 80 participants, and a 2-week post-treatment follow-up period.

Study Overview

• Status: Completed
• Conditions: Migraine Headache
• Intervention / Treatment: Combination product: INP104

Detailed Description

This is an outpatient study in people who currently suffer a minimum of 2 migraines per month. During the study, participants will be instructed to use no more than 2 doses of the study drug INP104 within a 24-hour period, or 3 doses in a 7-day period. Participants will self-administer INP104 nasally and record their migraines in an eDiary.

• Study Type: Interventional
• Enrollment (Actual): 360
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Synexus - Clinical Research Advantage, Inc. - Simon Williamson Clinical, PC., 832 Princeton Avenue Southwest
    • Birmingham, Alabama, United States, 35235
      • Alabama Clinical Therapeutics, LLC., 52 Medical Park East Drive, Suite 203
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Synexus - Radiant Research, Inc. - Phoenix SE, 2081 West Frye Road
    • Phoenix, Arizona, United States, 85020
      • Synexus - Clinical Research Advantage, Inc., Central Phoenix Medical Clinic, LLC., 7600 North 15th Street, Suite 191
  • California
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network, LLC., 2600 Redondo Avenue, Suite 415
    • Oceanside, California, United States, 92056
      • Excell Research, 3998 Vista Way
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Synexus - Clinical Research Advantage, Inc. - Colorado Springs Family Practice, 2960 North Circle Drive, Suite 200
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc., 5200 Belfort Road, Suite 420
    • Orlando, Florida, United States, 32801
      • Clinical Neuroscience Solutions, Inc., 618 East South Street, Suite 100
    • Tampa, Florida, United States, 33634
      • Meridien Research - Tampa, 5411 Beaumont Center Boulevard, Suite 760
    • West Palm Beach, Florida, United States, 33407
      • ENT Associates of South Florida, 4631 North Congress Avenue, Suite 200
    • Winter Haven, Florida, United States, 33880
      • Clinical Research of Central Florida, 500 East Central Avenue
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Synexus - Atlanta, 6065 Roswell Road, Suite 820
  • Illinois
    • Chicago, Illinois, United States, 60607
      • Cedar Crosse Research Center, 800 South Wells Street, Suite M-15
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Synexus - Clinical Research Advantage, Inc. - Allaw, 958C S. Kenmore Drive
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Central Kentucky Research Associates, Inc., 3475 Richmond Road, 3rd Floor
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research, LLC., 1111 Medical Center Boulevard, N513
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Synexus - Radiant Research, Inc., - Minneapolis, 7250 France Avenue South, Suite 417
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Synexus - Radiant Research, Inc. - St. Louis, 675 Old Ballas Road, Suite 103
    • Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research, LLC., 3862 Mexico Road
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Synexus - Clinical Research Advantage, Inc. - Omaha, 11020 Prairie Brook Road
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Synexus - Clinical Research Advantage, Inc. - Rita B. Chuang, MD, LLC., 2629 West Horizon Ridge Parkway, Suite 130
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute, 175 Cross Keys Road, Suite 300B
  • New York
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials, 3288 Ocean Avenue, Unit # MO
    • Jamaica, New York, United States, 11432
      • CNS Research Science, Inc., 80-15 164th Street
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research, 99 North Brice Road, Suite 260
  • Oklahoma
    • Edmond, Oklahoma, United States, 73034
      • OK Clinical Research, LLC., 120 North Bryant Avenue, Suite A5
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Research Network Oregon, 2701 North West Vaughn Street, Suite 350
  • Pennsylvania
    • Smithfield, Pennsylvania, United States, 15478
      • Frontier Clinical Research, LLC., 100 Ridge View Drive, Unit 4
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Coastal Carolina Research Center, 9279 Medical Plaza Drive, Suite B2
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • MR - ClinSearch, LLC., 6035 Shallowford Road, Suite 109
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc., 6401 Poplar Avenue, Suite 420
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology, 5508 Parkcrest Drive, Suite 300
    • Plano, Texas, United States, 75093
      • Synexus - Clinical Research Advantage, Inc. - Plano Internal Medicine Associates, PA., 6300 West Parker Road, Suite 220
  • Utah
    • Murray, Utah, United States, 84123
      • Synexus - Radiant Research, Inc. - Salt Lake City, 5251 South Green Street, Suite 300B
  • Virginia
    • Richmond, Virginia, United States, 23294
      • National Clinical Research, Inc., 2809 Emerywood Parkway, Suite 140

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented diagnosis of migraine with or without aura, with at least 2 attacks per month for the previous 6 months.
• Participants must be in good general health, with no significant medical history (excluding migraine).
• Participants must have the ability and willingness to attend the necessary visits at the study center.
• Participants must be able to provide the written informed consent prior to entry into the study.
• Women of childbearing potential must agree to use adequate contraception (as defined in the protocol and by study personnel) during the study and for 30 days after the last dose fo the study drug.
• Male participants and their partners must agree to use effective contraception (as defined in the protocol and by study personnel) during the study and for 30 days after the last dose of the study drug. Male participants should also refrain from sperm donation for 30 days after study completion.

Exclusion Criteria:

• Subjects with trigeminal autonomic cephalalgias (including cluster headache, hemicrania syndromes and short-lasting unilateral, neuralgiform headache attacks with conjunctival injection and tearing), hemiplegic migraine, or migraine with brainstem aura (previously referred to as basilar migraines).
• Subjects with chronic migraines, medication overuse headache or other chronic headache syndromes.
• Subjects with ischemic heart disease or subjects with clinical symptoms or findings consistent with coronary artery vasospasm, including Prinzmetal's variant angina.
• Subjects with significant risk factors for coronary artery disease (CAD) including current use of nicotine-containing products, medical history of diabetes, uncontrolled hypertension (high blood pressure), known peripheral arterial disease, Raynaud's phenomenon, sepsis or vascular surgery (within 3 months prior to study start), or severely impaired hepatic or renal (kidney) function.
• Subjects with recurrent sinusitis or epistaxis.
• Subjects with a history or presence of alcoholism or drug abuse within 2 years prior to first study drug administration.
• Women who are pregnant, or planning to get pregnant, or who are lactating while participating in the study.
• Use of any medications prohibited by protocol.
• Use of >12 days per month of triptan or ergot-based medication in the 2 months prior to screening.

Other protocol-defined inclusion/exclusion criteria may apply.

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: INP104; 24-week treatment period for all participants followed by a 28-week treatment extension period for a subset of participants	Combination product: INP104; No more than 2 doses within 24 hours, 3 doses within 7 days. 1.45 mg in a divided dose, one actuation per nostril.; Other Names: Dihydroergotamine Mesylate (DHE) administered using the I123 Precision Olfactory Delivery (POD) Device; INP104, POD-DHE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events (SAEs)	Number of participants with Serious Adverse Events (SAEs) whether or not related to study drug.	From study enrollment up to Week 26 (for the 24-Week Treatment Group) and up to Week 54 (for the 52-WeekTreatment Group)
Number of Participants With Non-serious Treatment Emergent Adverse Events (AEs)	Number of participants with non-serious treatment emergent adverse events (AEs), whether or not related to study drug.	From first use of INP104 up to Week 26 (for the 24-Week Treatment Group) and up to Week 54 (for the 52-WeekTreatment Group)
Change in Nasal Mucosa	Mean change from baseline in Quantitative Scoring Scale for Evaluation of the Nasal Mucosa (QSS-NM) score, reported at designated intervals on study. This scale was scored by otolaryngologists during routine endoscopy of the upper nasal cavity of participants. A minimum score of 0 means no issues were detected. A maximum score of 34 indicates severe issues (worse outcome).	Baseline up to Week 24 (for the 24-Week Treatment Group) and Baseline up to Week 52 (for the 52-WeekTreatment Group)
Change in Olfactory Function	Mean change from baseline in olfactory function score, assessed using the University of Pennsylvania Smell Identification Test (UPSIT), and reported at designated intervals on study. The UPSIT is a 40 question scratch and sniff test of olfactory function. The minimum score of 0 indicates worst olfactory function, and the maximum score of 40 indicates the highest level of olfactory function detectable by the test.	Baseline up to Week 24 (for the 24-Week Treatment Group) and Baseline up to Week 52 (for the 52-WeekTreatment Group)

Collaborators and Investigators

• Sponsor: Impel Pharmaceuticals

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2018
• Primary Completion (Actual): March 17, 2020
• Study Completion (Actual): March 17, 2020

Study Registration Dates

• First Submitted: June 4, 2018
• First Submitted That Met QC Criteria: June 4, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): March 11, 2021
• Last Update Submitted That Met QC Criteria: February 12, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Dopamine Agonists; Dopamine Agents; Vasoconstrictor Agents; Dihydroergotamine
• Other Study ID Numbers: INP104-301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes