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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 36
- 试验地点
- 1
- 主要终点
- DHE pharmacokinetics
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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 -
- •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.
研究组 & 干预措施
INP104
Single dose 1.45 mg Dihydroergotamine Mesylate (DHE), administered by I123 Precision Olfactory Delivery (POD) device nasal spray (INP104)
干预措施: INP104 (Combination Product)
D.H.E. 45 Injection (IV)
Single dose 1 mg Dihydroergotamine Mesylate (DHE) for intravenous injection
干预措施: Dihydroergotamine Mesylate (DHE) (Drug)
Migranal Nasal Spray
Single dose 2 mg Migranal Nasal Spray Dihydroergotamine Mesylate (DHE)
干预措施: Migranal Nasal Spray (Combination Product)
结局指标
主要结局
DHE pharmacokinetics
时间窗: 48 hours
CL/F (CL for IV administration)
次要结局
- Incidence of treatment-emergent adverse events(Day 1 to day 22 post first dosing)
- 8'-OH-DHE pharmacokinetics(48 hours)