Study to Compare the Pharmacodynamics and Pharmacokinetics of Acetylsalicylic Acid Powder for Oral Inhalation With Non-enteric-coated Chewable Aspirin in Healthy Adults.

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare the pharmacodynamics (PD), pharmacokinetics (PK), safety, and tolerability of acetylsalicylic acid powder for oral inhalation (i-ASA) with non-enteric-coated chewable aspirin (C-ASA) in healthy adults by demonstrating bioequivalence. In the first treatment period, subjects will be randomized to receive either a single dose (100 mg) of I-ASA powder via a Dry Powder Inhaler (DPI) OR a single dose (162 mg) of C-ASA tablets. After a washout period, subjects will be crossed over to receive the other treatment in the second treatment period. All subjects will receive both treatments during the study. Each single dose treatment will be followed by up to 24 hours of serial post-dose PK, PD, and safety/tolerability assessments.

Official Title
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A Single-dose, Open-label, Randomized, Multi-center, 2-treatment Crossover Study to Compare the Pharmacodynamics, Pharmacokinetics, Safety, and Tolerability of Acetylsalicylic Acid Powder for Oral Inhalation With Non-enteric-coated Chewable Aspirin in Healthy Adults

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: ASA
* Drug: non-enteric-coated chewable aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, ≥18 and ≤55 years of age, with BMI >18.5 and <32.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females. Healthy as defined by: the absence of clinically significant illness and surgery within 4 weeks prior to dosing. the absence of clinically significant history of neurological, endocrine, cardiovascular, pulmonary, respiratory, hematological (e.g., thrombocytopenia, neutropenia, bleeding disorders), immunological, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease. Female subjects of non-childbearing potential must be: post-menopausal OR surgically sterile at least 3 months prior to dosing. Sexually active female subjects of childbearing potential must be willing to use an acceptable contraceptive method throughout the study as defined in the protocol. Current non-smoker: no use of tobacco or nicotine products, including any smoking cessation nicotine-containing products (i.e., nicotine replacement therapy [patch, spray, inhaler, gum, lozenge, bupropion SR, clonidine and nortriptyline], e-cigarettes, etc.) for at least 3 months prior to screening. Agrees to refrain from alcohol consumption for at least 48 hours prior to admission and 48 hours after drug administration of each period. Able to understand the study procedures and provide signed informed consent to participate in the study. Exclusion Criteria: Any clinically significant abnormal finding at physical examination at screening. Positive serology test results for HBsAg, HCV antibody, or HIV antigen and antibody, at screening. Positive pregnancy test or lactating female subject. Positive urine drug screen, urine cotinine test, or alcohol breath test. Known allergic reactions, hypersensitivity or contraindications to aspirin (ASA), ibuprofen, other NSAIDs, or other related drugs, or to any excipient in the formulation. Known lack of response (lack of effect) to aspirin in the past. Clinically significant x-ray, ECG abnormalities or vital signs abnormalities at screening. Clinically significant abnormal laboratory parameters including: Hematocrit value ≤ 32%; Platelet count <142,000 or > 450,000 platelets per µL; ALT ≥ 3 x ULN; AST ≥ 3 x ULN. Subject with abnormal lung function defined by spirometric testing such that: the post bronchodilator FEV1 < 80% of predicted normal value OR FEV1/FVC ratio < 0.70. Subject with current asthma defined as post-bronchodilator FEV1 > 12% increase AND > 200 ml absolute increase from pre-bronchodilator values. Other protocol-defined I/E criteria that apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: I-ASA 100mg, then C-ASA 162mg tablet<br>Treatment A: Single dose of 100 mg ASA powder for oral inhalation (I-ASA) via DPI. Treatment B: Single dose of 162 mg chewable non-enteric-coated Aspirin (C-ASA). | Drug: ASA<br>* powder for oral inhalation via a Dry Powder Inhaler (DPI)<br>Drug: non-enteric-coated chewable aspirin<br>* Orally administered<br>|
| Experimental: Arm 2: C-ASA 162mg tablet, then I-ASA 100mg<br>Treatment A: Single dose of 162 mg chewable non-enteric-coated Aspirin (C-ASA). Treatment B: Single dose of 100 mg ASA powder for oral inhalation (I-ASA) via DPI. | Drug: ASA<br>* powder for oral inhalation via a Dry Powder Inhaler (DPI)<br>Drug: non-enteric-coated chewable aspirin<br>* Orally administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum thromboxane B2 (TxB2) serum concentration - Area under the effect curve (AUEC) of the % Change from baseline (CFB) in serum TxB2 concentration (TxB2 suppression) |  | 24 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving significant inhibition of platelet aggregation (<550 Aspirin Reaction Units [ARU]) |  | 2 minutes post-dose | 
| TxB2 serum concentration - AUEC of the % CFB in serum TxB2 concentration (TxB2 suppression) |  | 20 minutes post-dose. | 
| TxB2 serum concentration - AUEC of the % CFB in serum TxB2 concentration (TxB2 suppression) |  | 30 minutes post-dose | 
| Time to significant inhibition of platelet aggregation (<550 ARU). |  | assessed up to 24 hours post-dose | 
| Peak plasma concentrations (Cmax) of ASA | PK endpoints | pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440 | 
| Peak plasma concentrations (Cmax) of SA | PK endpoints | pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440 | 
| Area under the plasma concentration versus time curve (AUC0-inf) | PK endpoints | pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440 | 
| Area under the plasma concentration versus time curve (AUC0-t) | PK endpoints | pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440 | 
| Time to peak plasma concentrations (Tmax) of ASA | PK endpoints | pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440 | 
| Time to peak plasma concentrations (Tmax) of SA | PK endpoints | pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440 | 
| Incidence and frequency of Adverse Events. |  | screening through the 7-day to follow-up period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASA, acetylsalicylic acid, cyclooxygenase-1 enzyme, oral inhalation, inhaled, myocardial Infarction