A Study Evaluating the Safety, Tolerability and Pharmacokinetics of ASY202 in Healthy Adults

A Phase-1, Open-label Randomized, 4-treatment, 4-period Crossover Study to Evaluate the Pharmacokinetics, Relative Bioavailability, Safety and Tolerability of Single Doses of Dihydroergotamine Mesylate (DHE) Inhalation Powder, DHE Intravenous (IV), and DHE Nasal Spray in Healthy Adult Subjects.

A Phase 1 clinical trial to evaluate the pharmacokinetics, relative bioavailability, safety and tolerability of DHE inhalation powder delivered by dry powder inhaler, DHE IV, and DHE nasal spray.

Study Overview

• Status: Completed
• Conditions: Safety, and Tolerability
• Intervention / Treatment: Combination product: DHE inhalation powder low dose administered via dry powder inhaler (DPI) device; Combination product: DHE inhalation powder high dose administered via dry powder inhaler (DPI) device; Drug: DHE injected intravenously (1 mg); Drug: Metoclopramide 10mg; Drug: DHE 2 mg administered by nasal spray (Migranal®)

Detailed Description

This is an open-label, randomized, 4-treatment, 4-period crossover study to evaluate the PK, relative BA, safety, and tolerability of single doses of study medication in healthy adult subjects.

Following screening, eligible subjects will be enrolled and randomized to one of the 4 treatment sequences. Subjects will receive single doses of DHE inhalation powder (low dose and high dose), DHE IV (1 mg) and DHE nasal spray (2 mg).

Subjects will be administered one treatment in each period according to their assigned sequence. Each subject will receive all 4 treatments in the study.

During each treatment period subjects will remain in the clinical research unit for 3 days, until completion of the 48-hour post-dose assessments.

Subjects will return for their next treatment period after at least 7 days washout after the administration of their previous treatment until all periods have been completed in their sequence.

A follow-up will be conducted on Day 7 after the last dose in the study to assess safety.

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Alliance for Multispecialty research (AMR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Subjects must meet all the following criteria to be included in the study:

  1. Male or female, ≥ 18 and ≤ 55 years of age, with body mass index (BMI) >18.5 and < 32.0 kg/m2
  2. Healthy subjects
  3. Female subjects of non-childbearing potential or childbearing potential willing to use protocol required methods of contraception
  4. Current non-smoker
  5. Able to understand the study procedures and provide signed informed consent to participate in the study.

Exclusion Criteria:

• Subjects to whom any of the following applies will be excluded from the study:

  1. Positive pregnancy test or lactating female subjects at screening or on Day 1 of each treatment period
  2. Clinically significant abnormal laboratory or serology test results
  3. History or current diagnosis of uncontrolled or significant cardiac disease
  4. Significant risk factors for cardiovascular disease
  5. Subject with abnormal lung function at screening
  6. History or current diagnosis of lung disease e.g. asthma, COPD
  7. Known allergic reactions, hypersensitivity or contraindications to DHE, other ergot-derived products or to any excipient
  8. History of drug or alcohol abuse

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: inhaled DHE low dose; Low dose of DHE inhalation powder	Combination product: DHE inhalation powder low dose administered via dry powder inhaler (DPI) device; The DHE inhalation powder is a pre-metered drug-device combination product containing DHE dry powder low dose formulation for oral inhalation
Experimental: Treatment B: inhaled DHE high dose; High dose of DHE inhalation powder	Combination product: DHE inhalation powder high dose administered via dry powder inhaler (DPI) device; The DHE inhalation powder is a pre-metered drug-device combination product containing DHE dry powder high dose formulation for oral inhalation
Active Comparator: Treatment C: intravenous DHE; 1 mg DHE injected intravenously	Drug: DHE injected intravenously (1 mg); A single dose of DHE injection consists of 1 mg/mL ampoule of DHE solution for slow intravenous administration.; Drug: Metoclopramide 10mg; To prevent nausea caused by IV administration of DHE, participants will receive antiemetic pre-medication with metoclopramide 10 mg administered by slow intravenous push over 1-2 min, given 5 to 10 minutes prior to IV DHE dosing.
Active Comparator: Treatment D: intranasal DHE; 2 mg DHE nasal spray (Migranal®)	Drug: DHE 2 mg administered by nasal spray (Migranal®); A single vial of DHE nasal spray (Migranal®) contains 1 mL of 4 mg/mL DHE solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics: Area under the curve (AUC 0-t) of DHE	Area under the concentration-time curve from time zero until the last observed plasma concentration of DHE (AUC 0-t)	For each of the 4 treatment periods on baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Area under the curve (AUC 0-inf) of DHE	Area under the concentration-time curve from time zero to infinity (extrapolated) of plasma concentrations of DHE (AUC 0-inf)	For each of the 4 treatment periods on baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Peak plasma concentration (C max) of DHE	Maximal observed plasma concentration of DHE (C max)	For each of the 4 treatment periods on baseline and post-dose measurements from 2 minutes up to 48 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Number of participants with adverse events	Adverse events will be recorded and evaluated for their seriousness, severity and relationship to the study drug	From the time of signing the informed consent until the last visit on Day 7 after the last treatment period
Physical examination	Physical examination (including oral cavity, nasal cavity and injection site examination) will be performed	At screening, and for each of the 4 treatment periods at baseline, and post-dose at day 2 and day 3
Lung function by spirometry : Forced Expiratory Volume in 1 sec in % of predicted normal (FEV1 )	Effect of DHE on lung function will be measured by collecting FEV 1 pre- and post-dose at specified timepoints and will be analyzed by FEV1 < 70 % of predicted normal and/or comparison of pre- and post-dose > 20 % decline in FEV1.	At screening, and for each of the 4 treatment periods at pre-dose, and post-dose up to 48 hours
Lung function by spirometry : Forced Vital Capacity (FVC) in liters	Effect of DHE on lung function will be measured by collecting Forced Vital Capacity pre- and post-dose at specified timepoints	At screening, and for each of the 4 treatment periods at pre-dose, and post-dose up to 48 hours
Lung function by spirometry : FEV1/FVC ratio	Effect of DHE on lung function will be measured by collecting the FEV1/FVC ratio pre- and post-dose at specified timepoints	At screening, and for each of the 4 treatment periods at pre-dose, and post-dose up to 48 hours
Lung function by spirometry : Forced Expiratory Flow 25-75 in %	Effect of DHE on lung function will be measured by collecting the mean Forced expiratory Flow between 25% and 75% of the forced vital capacity pre- and post-dose at specified timepoints	At screening, and for each of the 4 treatment periods at pre-dose, and post-dose up to 48 hours
Clinical laboratory tests blood and urine	Change from baseline in clinical laboratory tests (including hematology, biochemistry, coagulation, and urinalysis) will be analyzed at different timepoints	At screening, and for each of the 4 treatment periods at pre-dose, and post-dose up to 48 hours
Pharmacokinetics: Area under the curve (AUC 0-t) of 8'-OH-DHE	Area under the concentration-time curve from time zero until the last observed plasma concentration of 8'-OH-DHE (AUC 0-t)	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Area under the curve (AUC 0-inf) of 8'-OH-DHE	Area under the concentration-time curve from time zero to infinity (extrapolated) of plasma concentrations of 8'-OH-DHE (AUC 0-inf)	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Peak plasma concentration (C max) of 8'-OH-DHE	Maximal plasma observed concentration of 8'-OH-DHE (C max)	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Time of peak maximal concentration (T max) of DHE and 8'-OH-DHE	Time when the maximal plasma concentration of DHE and 8'-OH-DHE are observed (T max)	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Terminal elimination half-life (T 1/2 el) of DHE and 8'-OH-DHE	Terminal elimination half-life of plasma concentrations of DHE and 8'-OH-DHE (T 1/2 el)	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Area under the curve (AUC 0-30 min) of DHE	Area under the concentration-time curve from time zero to 30 min of plasma concentrations of DHE (AUC 0-30min)	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Area under the curve (AUC 0-2 hours) of DHE	Area under the concentration-time curve from time zero to 2 hours of plasma concentrations of DHE (AUC 0-2 hours)	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Apparent clearance of DHE (CL/F)	Apparent clearance of DHE (CL/F) for DHE inhalation powder and DHE nasal spray Migranal®	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Clearance of DHE (CL)	Clearance of DHE for intravenous DHE (CL)	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Apparent volume of distribution of DHE (Vz/F)	Apparent volume of distribution (Vz/F) during terminal phase of DHE for DHE inhalation powder and DHE nasal spray Migranal®	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Pharmacokinetics: Volume of distribution of DHE (Vz)	Volume of distribution (Vz) of DHE intravenous	For each of the 4 treatment periods on Baseline and post-dose measurements from 2 minutes up to 48 hours
Safety: Blood pressure in mmHg	The changes from baseline in systolic and diastolic blood pressure will be assessed	Baseline and post-dose measurements from 10 minutes up to 48 hours for each of the 4 treatment periods
Safety: Heart rate in beats/min	The changes from baseline in heart rate will be assessed	Baseline and post-dose measurements from 10 minutes up to 48 hours for each of the 4 treatment periods
Safety: Respiratory rate in breaths/min	The changes from baseline in respiratory rate will be assessed	Baseline and post-dose measurements from 10 minutes up to 48 hours for each of the 4 treatment periods
Safety: Oral body temperature in degree Celsius	The changes from baseline in oral body temperature will be assessed	Baseline and post-dose measurements from 10 minutes up to 48 hours for each of the 4 treatment periods
ECG PR interval in msec	The changes from baseline in 12-lead ECG PR interval will be assessed	Baseline and post-dose measurements from 10 minutes up to 4 hours for each of the 4 treatment periods
ECG QRS complex in msec	The changes from baseline in 12-lead ECG QRS complex will be assessed	Baseline and post-dose measurements from 10 minutes up to 4 hours for each of the 4 treatment periods
ECG QT interval in msec	The changes from baseline in 12-lead ECG QT interval and Fridericia's corrected QT interval will be assessed	Baseline and post-dose measurements from 10 minutes up to 4 hours for each of the 4 treatment periods

Collaborators and Investigators

• Sponsor: Aspeya Switzerland SA

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2025
• Primary Completion (Actual): October 2, 2025
• Study Completion (Actual): October 2, 2025

Study Registration Dates

• First Submitted: October 28, 2025
• First Submitted That Met QC Criteria: November 7, 2025
• First Posted (Actual): November 10, 2025

Study Record Updates

• Last Update Posted (Actual): March 19, 2026
• Last Update Submitted That Met QC Criteria: March 17, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Inhalation powder; Dihydroergotamine mesylate
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Hydrocarbons, Cyclic; Carboxylic Acids; Hydroxy Acids; Alkaloids; Hydrocarbons, Aromatic; Amides; Phenols; Benzene Derivatives; Heterocyclic Compounds, 4 or More Rings; Acids, Carbocyclic; para-Aminobenzoates; Aminobenzoates; Benzoates; Hydroxybenzoates; Phenyl Ethers; Benzamides; Chlorobenzoates; Ergotamines; Ergot Alkaloids; Hydroxybenzoate Ethers; Metoclopramide; Dihydroergotamine
• Other Study ID Numbers: VFC202-102

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: No