Bioavailability of DHE Administered by I123 POD Device, IV Injection, and Migranal Nasal Spray in Healthy Adults
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT03401346 |
Recruitment Status :
Completed
First Posted : January 17, 2018
Last Update Posted : March 15, 2019
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 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 |

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 |
- DHE pharmacokinetics [ Time Frame: 48 hours ]Cmax
- DHE pharmacokinetics [ Time Frame: 48 hours ]Tmax
- DHE pharmacokinetics [ Time Frame: 48 hours ]AUC(0-t)
- DHE pharmacokinetics [ Time Frame: 48 hours ]kel
- DHE pharmacokinetics [ Time Frame: 48 hours ]T(1/2)
- DHE pharmacokinetics [ Time Frame: 48 hours ]AUC(0-inf)
- DHE pharmacokinetics [ Time Frame: 48 hours ]CL/F (CL for IV administration)
- 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
- 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]Cmax
- 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]Tmax
- 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]AUC(0-t)
- 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]kel
- 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]T(1/2)
- 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]AUC(0-inf)
- 8'-OH-DHE pharmacokinetics [ Time Frame: 48 hours ]CL/F (CL for IV administration)

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

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
Australia, Victoria | |
Centre for Clinical Studies/Nucleus Network | |
Melbourne, Victoria, Australia, 3004 |
Principal Investigator: | Jason Lickliter, MD | Centre for Clinical Studies/Nucleus Network |
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 |
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 |
Migraine Disorders Headache Pain Neurologic Manifestations 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 |