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Bioavailability of DHE Administered by I123 POD Device, IV Injection, and Migranal Nasal Spray in Healthy Adults

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ClinicalTrials.gov Identifier: NCT03401346
Recruitment Status : Completed
First Posted : January 17, 2018
Last Update Posted : March 15, 2019
Sponsor:
Information provided by (Responsible Party):
Impel NeuroPharma Inc.

Study Description
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Brief Summary:

A Phase I clinical trial to compare the bioavailability of dihydroergotamine mesylate (DHE) following a single dose administration of INP104 (DHE administered by I123 Precision Olfactory Delivery (POD) Device Nasal Spray) to that of D.H.E. 45 for Injection (Intravenous) and Migranal Nasal Spray in healthy adult subjects.

It is hypothesized that INP104 will address the current variability in nasal administration and give more reproducible dose delivery compared to Migranal nasal spray.

Blood concentrations of all three investigational products will be compared for 48 hours following dosing. The safety and tolerability of INP104 will be monitored throughout the study.

INP104 has been developed for the treatment of acute migraine headache. The device in which the drug will be delivered has been designed to deliver the medication to the upper nasal cavity with minimal variation in dose absorption, eg loss via dripping out of the nose or the dose being swallowed.

Approximately 36 participants in general good health (equal ratio of males and females desired) will be enrolled and will be allocated to receive 3 treatments in a randomized sequence. They will receive a single dose of INP104, a single dose of DHE via intravenous injection, and a single dose of Migranal Nasal Spray. There will be a wash out period where no treatment will be administered for 7 days in between each treatment. Participants are required to attend 3 inpatient periods and 1 final outpatient visit. Each participant will be in the study for up to 43 days.


Condition or disease Intervention/treatment Phase
Migraine Headache Combination Product: INP104 Drug: Dihydroergotamine Mesylate (DHE) Combination Product: Migranal Nasal Spray Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Three-Period, Three-Way, Randomized, Open-Label, Single-Dose, Cross-Over, Comparative Bioavailability Study of Dihydroergotamine Mesylate (DHE) Administered by I123 Precision Olfactory Delivery (POD) Device Nasal Spray, DHE for Injection (Intravenous), and Migranal® Nasal Spray in Healthy Adult Subjects
Actual Study Start Date : October 19, 2017
Actual Primary Completion Date : December 1, 2017
Actual Study Completion Date : December 6, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Headache

Arms and Interventions
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Arm Intervention/treatment
Experimental: INP104
Single dose 1.45 mg Dihydroergotamine Mesylate (DHE), administered by I123 Precision Olfactory Delivery (POD) device nasal spray (INP104)
 Combination Product: INP104
Dihydroergotamine Mesylate (DHE) administered via I123 Precision Olfactory Delivery (POD) Device
Active Comparator: D.H.E. 45 Injection (IV)
Single dose 1 mg Dihydroergotamine Mesylate (DHE) for intravenous injection
 Drug: Dihydroergotamine Mesylate (DHE)
Dihydroergotamine Mesylate (DHE) injection (intravenous)
Active Comparator: Migranal Nasal Spray
Single dose 2 mg Migranal Nasal Spray Dihydroergotamine Mesylate (DHE)
 Combination Product: Migranal Nasal Spray
Dihydroergotamine Mesylate (DHE) delivered via Migranal Nasal Spray pump


Outcome Measures
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Primary Outcome Measures :
  1. DHE pharmacokinetics [ Time Frame: 48 hours ]
    Cmax

  2. DHE pharmacokinetics [ Time Frame: 48 hours ]
    Tmax

  3. DHE pharmacokinetics [ Time Frame: 48 hours ]
    AUC(0-t)

  4. DHE pharmacokinetics [ Time Frame: 48 hours ]
    kel

  5. DHE pharmacokinetics [ Time Frame: 48 hours ]
    T(1/2)

  6. DHE pharmacokinetics [ Time Frame: 48 hours ]
    AUC(0-inf)

  7. DHE pharmacokinetics [ Time Frame: 48 hours ]
    CL/F (CL for IV administration)


Secondary Outcome Measures :
  1. Incidence of treatment-emergent adverse events [ Time Frame: Day 1 to day 22 post first dosing ]
    Incidence of treatment-emergent adverse events after one dose of INP-104, Migranal Nasal Spray or DHE45 by IV injection

  2. 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]
    Cmax

  3. 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]
    Tmax

  4. 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]
    AUC(0-t)

  5. 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]
    kel

  6. 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]
    T(1/2)

  7. 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]
    AUC(0-inf)

  8. 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]
    CL/F (CL for IV administration)


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Adult male and females, 18 to 55 years of age (inclusive) at the time of screening.
  • Subjects must be in good general health, with no significant medical history (including migraine), have no clinically significant abnormalities on physical examination at screening, and/or before administration of the initial dose of investigational product.
  • Subjects must have a Body Mass Index (BMI) between 18 and 32 kg/m2, inclusive.
  • Subjects must have clinical laboratory values within normal range as specified by the testing laboratory, or assessed as not clinically significant by the Principal Investigator.
  • Negative urine drug screen/alcohol breath test at screening.
  • Subjects who are willing to refrain from smoking for the duration of the study.

Exclusion Criteria:

  • Subjects with a recent history of migraine and its variants including hemiplegic migraine and basilar migraine. A recent history of migraine is defined as (a) current or past history of migraine with at least 1 attack in last 6 months or (b) those receiving antimigraine prophylaxis.
  • Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV).
  • Subjects who have ingested caffeine within 48 hours before admission on Day -1. Subjects must also agree to refrain from consumption of caffeinated drinks for 48 hours before admission of Days 7 and 14 (i.e. prior to each subsequent dosing), and throughout confinement.
  • Subjects with ischemic heart disease or subjects who have clinical symptoms or findings consistent with coronary artery vasospasm including Prinzmetal's variant angina.
  • Subjects with hypertension, known peripheral arterial disease, Raynaud's phenomenon, sepsis, history of vascular surgery or severely impaired hepatic or renal function
  • Subjects who have previously shown hypersensitivity to ergot alkaloids or metoclopramide.
  • Use of any relevant prescription, over-the-counter medication (with the exception of oral contraceptives), foods (e.g. grapefruit juice) or supplements (including herbal) within 14 days of randomization [especially those affecting the Cytochrome P450 3A4 (CYP3A4) metabolic pathway].
  • History or presence of alcoholism or drug abuse within the 2 years prior to the first investigational product administration.
  • Surgery within the past three months prior to the first investigational product administration as determined by the PI to be clinically relevant.
  • Active infection and/or use of macrolide antibiotics within 14 days prior to enrollment.
  • History of recurrent infections.
  • Any nasal congestion or physical blockage in either nostril, or deviated nasal septum as determined by nasal examination.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03401346


Locations
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Australia, Victoria
Centre for Clinical Studies/Nucleus Network
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
Impel NeuroPharma Inc.
Investigators
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Principal Investigator: Jason Lickliter, MD Centre for Clinical Studies/Nucleus Network
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Impel NeuroPharma Inc.
ClinicalTrials.gov Identifier: NCT03401346    
Other Study ID Numbers: INP104-101
ACTRN12617001381370p ( Registry Identifier: ANZCTR )
First Posted: January 17, 2018    Key Record Dates
Last Update Posted: March 15, 2019
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: Yes
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Migraine Disorders
Headache
Pain
Neurologic Manifestations
Signs and Symptoms
Headache Disorders, Primary
Headache Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Dihydroergotamine
 Vasoconstrictor Agents
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents