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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03401346




Registration number
NCT03401346
Ethics application status
Date submitted
17/12/2017
Date registered
17/01/2018
Date last updated
15/03/2019

Titles & IDs
Public title
Bioavailability of DHE Administered by I123 POD Device, IV Injection, and Migranal Nasal Spray in Healthy Adults
Scientific 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
Secondary ID [1] 0 0
ACTRN12617001381370p
Secondary ID [2] 0 0
INP104-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Migraine Headache 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Combination Product - INP104
Treatment: Drugs - Dihydroergotamine Mesylate (DHE)
Combination Product - Migranal Nasal Spray

Experimental: INP104 - Single dose 1.45 mg Dihydroergotamine Mesylate (DHE), administered by I123 Precision Olfactory Delivery (POD) device nasal spray (INP104)

Active Comparator: D.H.E. 45 Injection (IV) - Single dose 1 mg Dihydroergotamine Mesylate (DHE) for intravenous injection

Active Comparator: Migranal Nasal Spray - Single dose 2 mg Migranal Nasal Spray Dihydroergotamine Mesylate (DHE)


Combination Product: INP104
Dihydroergotamine Mesylate (DHE) administered via I123 Precision Olfactory Delivery (POD) Device

Treatment: Drugs: Dihydroergotamine Mesylate (DHE)
Dihydroergotamine Mesylate (DHE) injection (intravenous)

Combination Product: Migranal Nasal Spray
Dihydroergotamine Mesylate (DHE) delivered via Migranal Nasal Spray pump

Intervention code [1] 0 0
Combination Product
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DHE pharmacokinetics - Cmax
Timepoint [1] 0 0
48 hours
Primary outcome [2] 0 0
DHE pharmacokinetics - Tmax
Timepoint [2] 0 0
48 hours
Primary outcome [3] 0 0
DHE pharmacokinetics - AUC(0-t)
Timepoint [3] 0 0
48 hours
Primary outcome [4] 0 0
DHE pharmacokinetics - kel
Timepoint [4] 0 0
48 hours
Primary outcome [5] 0 0
DHE pharmacokinetics - T(1/2)
Timepoint [5] 0 0
48 hours
Primary outcome [6] 0 0
DHE pharmacokinetics - AUC(0-inf)
Timepoint [6] 0 0
48 hours
Primary outcome [7] 0 0
DHE pharmacokinetics - CL/F (CL for IV administration)
Timepoint [7] 0 0
48 hours
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Day 1 to day 22 post first dosing
Secondary outcome [2] 0 0
8'-OH-DHE pharmacokinetics - Cmax
Timepoint [2] 0 0
48 hours
Secondary outcome [3] 0 0
8'-OH-DHE pharmacokinetics - Tmax
Timepoint [3] 0 0
48 hours
Secondary outcome [4] 0 0
8'-OH-DHE pharmacokinetics - AUC(0-t)
Timepoint [4] 0 0
48 hours
Secondary outcome [5] 0 0
8'-OH-DHE pharmacokinetics - kel
Timepoint [5] 0 0
48 hours
Secondary outcome [6] 0 0
8'-OH-DHE pharmacokinetics - T(1/2)
Timepoint [6] 0 0
48 hours
Secondary outcome [7] 0 0
8'-OH-DHE pharmacokinetics - AUC(0-inf)
Timepoint [7] 0 0
48 hours
Secondary outcome [8] 0 0
8'-OH-DHE pharmacokinetics - CL/F (CL for IV administration)
Timepoint [8] 0 0
48 hours

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Centre for Clinical Studies/Nucleus Network - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Impel NeuroPharma Inc.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03401346
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jason Lickliter, MD
Address 0 0
Centre for Clinical Studies/Nucleus Network
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications