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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
Other interventions - INP104
Treatment: Drugs - Dihydroergotamine Mesylate (DHE)
Other interventions - 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)


Other interventions: INP104
Dihydroergotamine Mesylate (DHE) administered via I123 Precision Olfactory Delivery (POD) Device

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

Other interventions: Migranal Nasal Spray
Dihydroergotamine Mesylate (DHE) delivered via Migranal Nasal Spray pump
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
DHE pharmacokinetics
Timepoint [1] 0 0
48 hours
Primary outcome [2] 0 0
DHE pharmacokinetics
Timepoint [2] 0 0
48 hours
Primary outcome [3] 0 0
DHE pharmacokinetics
Timepoint [3] 0 0
48 hours
Primary outcome [4] 0 0
DHE pharmacokinetics
Timepoint [4] 0 0
48 hours
Primary outcome [5] 0 0
DHE pharmacokinetics
Timepoint [5] 0 0
48 hours
Primary outcome [6] 0 0
DHE pharmacokinetics
Timepoint [6] 0 0
48 hours
Primary outcome [7] 0 0
DHE pharmacokinetics
Timepoint [7] 0 0
48 hours
Secondary outcome [1] 0 0
Incidence of treatment-emergent adverse events
Timepoint [1] 0 0
Day 1 to day 22 post first dosing
Secondary outcome [2] 0 0
8'-OH-DHE pharmacokinetics
Timepoint [2] 0 0
48 hours
Secondary outcome [3] 0 0
8'-OH-DHE pharmacokinetics
Timepoint [3] 0 0
48 hours
Secondary outcome [4] 0 0
8'-OH-DHE pharmacokinetics
Timepoint [4] 0 0
48 hours
Secondary outcome [5] 0 0
8'-OH-DHE pharmacokinetics
Timepoint [5] 0 0
48 hours
Secondary outcome [6] 0 0
8'-OH-DHE pharmacokinetics
Timepoint [6] 0 0
48 hours
Secondary outcome [7] 0 0
8'-OH-DHE pharmacokinetics
Timepoint [7] 0 0
48 hours
Secondary outcome [8] 0 0
8'-OH-DHE pharmacokinetics
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
Sex
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
19/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/12/2017
Sample size
Target
Accrual to date
Final
36
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 Pharmaceuticals
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/study/NCT03401346
Trial related presentations / 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.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03401346