Migraine HeadachePhase 1NCT03401346

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

A Phase 1 study testing INP104, Dihydroergotamine Mesylate (DHE) and Migranal Nasal Spray in people with Migraine Headache, run by Impel Pharmaceuticals at 1 site in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Migraine Headache
What is being tested?: INP104, Dihydroergotamine Mesylate (DHE) and Migranal Nasal Spray
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 1 siteAustralia
Study dates: 19 Oct 2017to 6 Dec 2017
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country.

Australia1 site

Centre for Clinical Studies/Nucleus Network
Melbourne, Victoria, 3004

Other trials in Australia

About this study

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

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.

Conditions: Migraine Headache
Being tested: INP104, Dihydroergotamine Mesylate (DHE), Migranal Nasal Spray
Medical subject headings: Migraine Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

INP104Combination product
Dihydroergotamine Mesylate (DHE) administered via I123 Precision Olfactory Delivery (POD) Device
Dihydroergotamine Mesylate (DHE)Drug
Dihydroergotamine Mesylate (DHE) injection (intravenous)
Migranal Nasal SprayCombination product
Dihydroergotamine Mesylate (DHE) delivered via Migranal Nasal Spray pump

Study groups in NCT03401346
Study group	Role	What they receive
INP104	Experimental	Single dose 1.45 mg Dihydroergotamine Mesylate (DHE), administered by I123 Precision Olfactory Delivery (POD) device nasal spray (INP104) Receives: Combination Product: INP104
D.H.E. 45 Injection (IV)	Active comparator	Single dose 1 mg Dihydroergotamine Mesylate (DHE) for intravenous injection Receives: Drug: Dihydroergotamine Mesylate (DHE)
Migranal Nasal Spray	Active comparator	Single dose 2 mg Migranal Nasal Spray Dihydroergotamine Mesylate (DHE) Receives: Combination Product: Migranal Nasal Spray

What is being measured

The primary outcome is the main question the study is designed to answer.

DHE pharmacokinetics
Cmax
Measured: 48 hours
DHE pharmacokinetics
Tmax
Measured: 48 hours
DHE pharmacokinetics
AUC(0-t)
Measured: 48 hours
DHE pharmacokinetics
kel
Measured: 48 hours
DHE pharmacokinetics
T(1/2)
Measured: 48 hours
DHE pharmacokinetics
AUC(0-inf)
Measured: 48 hours
DHE pharmacokinetics
CL/F (CL for IV administration)
Measured: 48 hours

Secondary outcomes (8)

Incidence of treatment-emergent adverse events
Incidence of treatment-emergent adverse events after one dose of INP-104, Migranal Nasal Spray or DHE45 by IV injection
Measured: Day 1 to day 22 post first dosing
8'-OH-DHE pharmacokinetics
Cmax
Measured: 48 hours
8'-OH-DHE pharmacokinetics
Tmax
Measured: 48 hours
8'-OH-DHE pharmacokinetics
AUC(0-t)
Measured: 48 hours
8'-OH-DHE pharmacokinetics
kel
Measured: 48 hours
8'-OH-DHE pharmacokinetics
T(1/2)
Measured: 48 hours
8'-OH-DHE pharmacokinetics
AUC(0-inf)
Measured: 48 hours
8'-OH-DHE pharmacokinetics
CL/F (CL for IV administration)
Measured: 48 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

19 Oct 20176 Dec 2017

First posted17 Jan 2018
Study start19 Oct 2017
Primary completion1 Dec 2017
Study completion6 Dec 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Migraine HeadacheStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03401346
Sponsor's protocol ID: INP104-101
Other IDs: ACTRN12617001381370p
Status last verified: Jan 2018
First submitted: 17 Dec 2017
Last updated: 15 Mar 2019
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: Yes
Individual data sharing: No

Publications

Shrewsbury SB, Jeleva M, Satterly KH, Lickliter J, Hoekman J. STOP 101: A Phase 1, Randomized, Open-Label, Comparative Bioavailability Study of INP104, Dihydroergotamine Mesylate (DHE) Administered Intranasally by a I123 Precision Olfactory Delivery (POD(R) ) Device, in Healthy Adult Subjects. Headache. 2019 Mar;59(3):394-409. doi: 10.1111/head.13476. Epub 2019 Jan 19.
PubMed 30659611

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Migraine Headache trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT03401346
Acronym / sponsor ID: INP104-101
Conditions: Migraine Headache
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: Impel PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: 19 Oct 2017 (actual)
Primary completion: 1 Dec 2017 (actual)
Study completion: 6 Dec 2017 (actual)
First posted: 17 Jan 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
INP104	Experimental	Combination Product: INP104Single dose 1.45 mg Dihydroergotamine Mesylate (DHE), administered by I123 Precision Olfactory Delivery (POD) device nasal spray (INP104)
D.H.E. 45 Injection (IV)	Active comparator	Drug: Dihydroergotamine Mesylate (DHE)Single dose 1 mg Dihydroergotamine Mesylate (DHE) for intravenous injection
Migranal Nasal Spray	Active comparator	Combination Product: Migranal Nasal SpraySingle dose 2 mg Migranal Nasal Spray Dihydroergotamine Mesylate (DHE)

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

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.

Key exclusion criteria (12 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
INP104Dihydroergotamine Mesylate (DHE) administered via I123 Precision Olfactory Delivery (POD) Device	Combination product	INP104
Dihydroergotamine Mesylate (DHE)Dihydroergotamine Mesylate (DHE) injection (intravenous)	Drug	D.H.E. 45 Injection (IV)
Migranal Nasal SprayDihydroergotamine Mesylate (DHE) delivered via Migranal Nasal Spray pump	Combination product	Migranal Nasal Spray

Primary outcome

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)

8 secondary outcomes

Incidence of treatment-emergent adverse events
Time frame: Day 1 to day 22 post first dosing
8'-OH-DHE pharmacokinetics
Time frame: 48 hours
8'-OH-DHE pharmacokinetics
Time frame: 48 hours
8'-OH-DHE pharmacokinetics
Time frame: 48 hours
8'-OH-DHE pharmacokinetics
Time frame: 48 hours
8'-OH-DHE pharmacokinetics
Time frame: 48 hours
8'-OH-DHE pharmacokinetics
Time frame: 48 hours
8'-OH-DHE pharmacokinetics
Time frame: 48 hours

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2019.
Derived from this study: PubMed 30659611Shrewsbury SB, Jeleva M, Satterly KH, Lickliter J, Hoekman J. STOP 101: A Phase 1, Randomized, Open-Label, Comparative Bioavailability Study of INP104, Dihydroergotamine Mesylate (DHE) Administered Intranasally by a I123 Precision Olfactory Delivery (POD(R) ) Device, in Healthy Adult Subjects. Headache. 2019 Mar;59(3):394-409. doi: 10.1111/head.13476. Epub 2019 Jan 19.
Individual participant dataSharing planned: No

Related trials for Migraine Headache

Active, not recruiting
App-Based Migraine Treatment: The Health enSuite Study
Migraine, Migraine With Aura
Enrolling by invitation
App-based Breathing Program for Migraine Relief
Migraine, Heart Rate Variability (HRV)
Recruiting
Headache Education and Awareness vs. Daily Mindfulness Strategies - Understanding Pain
Migraine, Migraine in Adolescence
Active, not recruiting
Intra-Nasal Mechanical Stimulation (INMEST) as a Potential Preventative Treatment for Migraine
Migraine
RecruitingPhase 3
Eary Infusion of Eptinezumab for TreatmEnt of ACute Post-Traumatic Headaches (ELITE-ACT)
Post Traumatic Headache

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Jason Lickliter, MD principal investigator

Centre for Clinical Studies/Nucleus Network

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing INP104, Dihydroergotamine Mesylate (DHE) and Migranal Nasal Spray in people with Migraine Headache, run by Impel Pharmaceuticals at 1 site in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

DHE pharmacokinetics (time frame: 48 hours). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03401346, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2019; AzTrials last refreshed its copy on 6 Nov 2026.