None listed
Conditions
Brief summary
This Phase I clinical trial will compare the bioavailability of dihydroergotamine mesylate (DHE) following a single dose administration of INP104 (DHE administered by I123 Precision Olfactory Delivery (POD TM) Device nasal spray to that of D.H.E. 45 for Injection (intravenous [IV]) 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 randomised sequence. They will receive a single dose of INP104 via the POD device, 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 at least 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.
Interventions
Arm 1: Single dose 1.45 mg Dihydroergotamine Mesylate (DHE), administered by I123 Precision Olfactory Delivery (POD TM) device nasal spray (INP104). The 'wash out' period between each treatment will be 7days.
Sponsors
Clinical Network Services (CNS) Pty Ltd
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Adult male and females, 18 to 55 years of age (inclusive) at the time of screening. 2. 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. 3. Subjects must have a Body Mass Index (BMI) between 18 and 32 kg/m2, inclusive. 4. 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. 5. Negative urine drug screen/alcohol breath test at screening. 6. Subjects who are willing to refrain from smoking for the duration of the study. 7. Female subjects of childbearing potential must agree to use 2 methods of adequate contraception during the study and for 30 days after the last dose of investigational product. A female of childbearing potential is defined as a premenopausal female capable of becoming pregnant. This includes women on oral, injectable, or mechanical contraception; women who are single; women whose husbands have been vasectomized or whose husbands have received or are utilizing mechanical contraceptive devices. 8. Male subjects and their partners must agree to use two forms of effective methods of contraception during the study and for 90 days after study completion.
Exclusion criteria
1. Subjects with a recent history of migraine and its variants including hemiplegic migraine and basilar migrane. 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. 2. Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV). 3. 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. 4. Subjects with ischemic heart disease or subjects who have clinical symptoms or findings consistent with coronary artery vasospasm including Prinzmetal’s variant angina. 5. Subjects with hypertension, known peripheral arterial disease, Raynaud’s phenomenon, sepsis, history of vascular surgery or severely impaired hepatic or renal function 6. Subjects who have previously shown hypersensitivity to ergot alkaloids. 7. Females who are pregnant or lactating. 8. Subjects with any underlying physical, psychological or medical condition that, in the opinion of the Investigator, would make it unlikely that they would comply with the study requirements. 9. 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]. 10. Abnormal, clinically significant laboratory tests. 11. History or presence of alcoholism or drug abuse within the 2 years prior to the first investigational product administration. 12. Blood donation or significant blood loss within 60 days prior to the first investigational product administration. 13. Plasma donation within 7 days prior to the first investigational product administration. 14. Administration of IP in another trial within 30 days or 5 half-lives (whichever is longer) prior to the first investigational product administration. 15. Surgery within the past three months prior to the first investigational product administration as determined by the PI to be clinically relevant. 16. Failure to satisfy the PI of fitness to participate for any other reason (including under the influence of alcohol or drugs of abuse). 17. Active infection and/or use of macrolide antibiotics within 14 days prior to enrolment. 18. History of recurrent infections. 19. Serious local infection or systemic infection within 3 months requiring antibiotic treatment. 20. Any acute illness within 30 days prior to Day 1, unless the subject has recovered from recent minor ailments. 21. Any nasal congestion or physical blockage in either nostril or deviated nasal septum as determined by nasal examination.
Outcome results
None listed