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

March 13, 2019 updated by: Impel Pharmaceuticals

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
DHE pharmacokinetics
Time Frame: 48 hours
Cmax
48 hours
DHE pharmacokinetics
Time Frame: 48 hours
Tmax
48 hours
DHE pharmacokinetics
Time Frame: 48 hours
AUC(0-t)
48 hours
DHE pharmacokinetics
Time Frame: 48 hours
kel
48 hours
DHE pharmacokinetics
Time Frame: 48 hours
T(1/2)
48 hours
DHE pharmacokinetics
Time Frame: 48 hours
AUC(0-inf)
48 hours
DHE pharmacokinetics
Time Frame: 48 hours
CL/F (CL for IV administration)
48 hours

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
Day 1 to day 22 post first dosing
8'-OH-DHE pharmacokinetics
Time Frame: 48 hours
Cmax
48 hours
8'-OH-DHE pharmacokinetics
Time Frame: 48 hours
Tmax
48 hours
8'-OH-DHE pharmacokinetics
Time Frame: 48 hours
AUC(0-t)
48 hours
8'-OH-DHE pharmacokinetics
Time Frame: 48 hours
kel
48 hours
8'-OH-DHE pharmacokinetics
Time Frame: 48 hours
T(1/2)
48 hours
8'-OH-DHE pharmacokinetics
Time Frame: 48 hours
AUC(0-inf)
48 hours
8'-OH-DHE pharmacokinetics
Time Frame: 48 hours
CL/F (CL for IV administration)
48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Impel Pharmaceuticals

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jason Lickliter, MD, Centre for Clinical Studies/Nucleus Network

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 19, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 6, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 17, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 16, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 17, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 15, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 13, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • INP104-101
  • ACTRN12617001381370p (Registry Identifier: ANZCTR)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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