A Study to Compare Zavegepant Concentration Using Samples Collected From the Vein Versus Patient-Centric Microsampling

Study Overview
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Brief Summary
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The purpose of this clinical trial is to learn about the pharmacokinetics and safety of a drug called zavegepant from samples collected using a patient-centric device called Tasso-Plus (for liquid blood sample collection) and Tasso-M20 (for dried blood sample collection) compared to standard venous sample collection. This study consists of two periods and will enroll approximately 14 healthy participants. In period 1, half of the enrolled participants (n=7) will use Tasso-Plus, and the other 50% (n=7) will use Tasso-M20. For each participant, PK samples will be collected after zavegepant administration in period 1 using the assigned Tasso device simultaneously with collecting venous blood samples. In addition, taste assessments will be performed at time intervals of 1 (immediately after dosing), 5, 10 and 20 minutes after zavegepant IN administration. Also, if feasible, 4 Japanese participants will be enrolled among those 14 participants to evaluate the PK and safety of zavegepant IN in Japanese vs. non Japanese participants. In period 2, a butterscotch candy will be given 5 minutes before administering the zavegepant IN study intervention. Taste assessment will also be performed after zavegepant IN administration with a butterscotch candy in period 2. For taste assessment, each participant will record the sensory attributes at timed intervals of 1 (immediately after dosing), 5, 10 and 20 minutes after zavegepant administration in each period. The expected duration of participation from screening until follow-up telephone contact is approximately 9 weeks.

Official Title
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A Pharmacokinetic Study of Zavegepant Intranasal in Healthy Adults Comparing Conventional Venous Blood Sampling With Patient-Centric Sampling

Conditions
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Healthy

Intervention / Treatment
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* Drug: Zavegepant 10 mg IN


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥18 years of age and older at the time of signing the informed consent document (ICD). Male and female participants who are overtly healthy as determined by medical evaluation. Body Mass Index (BMI) 16.0-32.0 kg/m2 and body weight ≥45.0 kg (99 lb). Females must not be breastfeeding or lactating and must have a negative urine or serum pregnancy test (minimum sensitivity 25 international units per liter [IU/L] or equivalent units of human chorionic gonadotropin [HCG]) at screening. Woman/women of childbearing potential (WOCBP) must have negative urine or serum pregnancy test at admission. Exclusion Criteria: Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing). Clinically significant history of nasal conditions that may affect the administration or absorption of the nasal product (eg, severe septum deviation or nasal deformity, inflammation, perforation, mucosal erosion, localized infection or ulceration, congestion, polyposis, rhinorrhea, nasal surgery within the previous 6 months, or nasal trauma). Significant history of seizure disorder other than a single childhood febrile seizure (eg, epilepsy) or history of gallstone or cholecystectomy. Any other medical or psychiatric condition, including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to coronavirus disease 2019 (COVID-19) pandemic that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study. Use of organic anion transporting polypeptide 1B3 (OATP1B3) inhibitors within 14 days or 5 half-lives, whichever is longer, before first dosing. Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to investigational product (IP) dosing, administration of a biological product in the context of a clinical research study within 90 days prior to IP dosing, or concomitant participation in an investigational study involving no drug or device administration. Any clinically significant abnormal laboratory test results or positive test found during medical screening. A single repeat for positive drug screen may be allowed at the discretion of the PI. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination or nasal inspection beyond what is consistent with the target population. Any reason that, in the opinion of the PI, would prevent the participant from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zavegepant 10 mg Intranasal (IN)<br>All participants will receive zavegepant 10 mg IN spray in period 1 and a butterscotch candy + zavegepant 10 mg IN spray in period 2 | Drug: Zavegepant 10 mg IN<br>* All participants will receive zavegepant 10 mg IN spray in period 1 and a butterscotch candy + zavegepant 10 mg IN spray in period 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Zavegepant Concentrations from Samples Collected Using Tasso Devices Versus Standard Venous Phlebotomyi |  | 0, 15, 30 minutes, 1, 1.5-, 2-, 3-, 4-, 6-, 8-, 12-, and 24-hour post-dose | 
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) if data permits |  | 0, 15, 30 minutes, 1, 1.5-, 2-, 3-, 4-, 6-, 8-, 12-, and 24-hour post-dose | 
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) |  | 0, 15, 30 minutes, 1, 1.5-, 2-, 3-, 4-, 6-, 8-, 12-, and 24-hour post-dose | 
| Maximum Observed Plasma Concentration (Cmax) |  | 0, 15, 30 minutes, 1, 1.5-, 2-, 3-, 4-, 6-, 8-, 12-, and 24-hour post-dose | 
| Time to Reach Maximum Observed Plasma Concentration (Tmax) |  | 0, 15, 30 minutes, 1, 1.5-, 2-, 3-, 4-, 6-, 8-, 12-, and 24-hour post-dose | 
| Plasma Decay Half-Life (t1/2) |  | 0, 15, 30 minutes, 1, 1.5-, 2-, 3-, 4-, 6-, 8-, 12-, and 24-hour post-dose | 
| Apparent Oral Clearance (CL/F) |  | 0, 15, 30 minutes, 1, 1.5-, 2-, 3-, 4-, 6-, 8-, 12-, and 24-hour post-dose | 
| Apparent Volume of Distribution (Vz/F) |  | 0, 15, 30 minutes, 1, 1.5-, 2-, 3-, 4-, 6-, 8-, 12-, and 24-hour post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of Treatment Emergent Adverse Events (TEAE's) |  | Screening to follow-up (Day 30 to 37) | 
| Number of Participants With Clinical Laboratory Abnormalities | including vital signs, blood pressure, pulse rate, and Electrocardiogram (ECG) parameters | Screening to follow-up (Day 30 to 37) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zavegepant, Migraine, Healthy Volunteers, Tasso