To Evaluate the Bioavailability of a Single Oral Dose of the Acetylsalicylic Acid Containing Dry Powder 500 mg in Comparison to the Bioavailability of a Single Oral Dose of Aspirin Tablets and Aspirin Effervescent Tablets in Healthy Adults.

Study Overview
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Brief Summary
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To evaluate the bioavailability of a single oral dose of the Acetylsalicylic Acid containing dry powder 500 mg in comparison to the bioavailability of a single oral dose of aspirin tablets and aspirin effervescent tablets in healthy adults.

Official Title
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An Open Label Crossover Pharmacokinetic Trial of Aspirin Dry Powder Versus Aspirin Tablets and Aspirin Effervescent Tablets in Healthy Adult Subjects

Conditions
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Pharmacology, Clinical

Intervention / Treatment
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* Drug: Aspirin (Acetylsalicylic acid, BAYe4465)
* Drug: Aspirin (Acetylsalicylic acid, BAYe4465)
* Drug: Aspirin (Acetylsalicylic acid, BAYe4465)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy ,male and female subjects 18 to 55 years of age, inclusive Body Mass Index (BMI) of approximately 18 to 30 kg/m2, and a total body weight >50 kg (110 lbs) Results of screening and clinical laboratory tests are within normal limits or considered not clinically significant by the Principal Investigator or Sponsor Female subjects of childbearing potential must be using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives), e.g., oral or patch contraceptives, intrauterine device, intramuscular injection or double-barrier and have a negative pregnancy test at Screening and on Day 0 of each treatment period. Female subjects of nonchildbearing potential must be amenorrheic for at least 2 years or had a hysterectomy and/or bilateral oophorectomy. Exclusion Criteria: History of hypersensitivity to acetylsalicylic acid (ASA), naproxen sodium, acetaminophen, other non-steroidal anti-inflammatory drugs (NSAIDs), and similar pharmacological agents or components of the products History of gastrointestinal bleeding or perforation, including bleeding related to previous NSAID therapy. Active, or history of recurrent peptic ulcer/hemorrhage (two or more distinct episodes of proven ulceration or bleeding). Have taken ASA, ASA-containing products, acetaminophen or any other NSAID (OTC or prescription) seven days prior to dosing or during the Treatment Periods, other than study product Loss of blood in excess of 500 mL within 56 days of the first dose of trial treatment (e.g., donation, plasmapheresis, or injury) Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic disease, or malignancies Positive alcohol or drug screen at Screening or on Day 0 of Treatment Periods 1,2 and 3 Females who are pregnant or lactating

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: Aspirin dry powder<br>500 mg Acetylsalicylic Acid (ASA) dry powder | Drug: Aspirin (Acetylsalicylic acid, BAYe4465)<br>* One stick pack containing 500 mg acetylsalicylic acid dry powder<br>|
| Active Comparator: Aspirin coated tablet<br>500 mg ASA coated tablet | Drug: Aspirin (Acetylsalicylic acid, BAYe4465)<br>* One tablet containing 500 mg acetylsalicylic acid<br>|
| Active Comparator: Aspirin effervescent tablet<br>500 mg ASA effervescent tablet | Drug: Aspirin (Acetylsalicylic acid, BAYe4465)<br>* One effervescent tablet containing 500 mg acetylsalicylic acid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of Acetylsalicylic Acid (ASA) characterized by AUC0-t |  | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Acetylsalicylic Acid (ASA) characterized by AUC0-∞ | AUC0-∞ : AUC from zero to infinity after single dose. | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Acetylsalicylic Acid (ASA) characterized by Cmax | Cmax: maximum drug concentration in plasma after single dose administration | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Acetylsalicylic Acid (ASA) characterized by tmax | tmax: time to reach maximum drug concentration in plasma after single (first) dose | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Acetylsalicylic Acid (ASA) characterized by λz (Kel) | λz (Kel) : Apparent terminal rate constant, calculated from the slope of a log-linear regression of the unweighted data considering the last concentration-time points > LLOQ | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose | 
| Plasma concentration of Acetylsalicylic Acid (ASA) characterized by t1/2 |  | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Acetylsalicylic Acid (ASA) characterized by t lag | t lag : Lag-time (time delay between drug administration and first observed concentration above LLOQ (Lower limit of quantification) | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Acetylsalicylic Acid (ASA) characterized by Cmax/AUC0-∞ |  | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Acetyl salicylic Acid (ASA) characterized by MRT | MRT :Mean residence time (for extravascular and iv bolus administration) | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Salicylic Acid (SA) characterized by AUC0-t |  | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Salicylic Acid (SA) characterized by AUC0-∞ | AUC0-∞ : AUC from zero to infinity after single dose | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Salicylic Acid (SA) characterized by Cmax | Cmax: maximum drug concentration in plasma after single dose administration | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Salicylic Acid (SA) characterized by tmax | tmax: time to reach maximum drug concentration in plasma after single (first) dose | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Salicylic Acid (SA) characterized by λz (Kel) | λz (Kel) : Apparent terminal rate constant, calculated from the slope of a log-linear regression of the unweighted data considering the last concentration-time points > LLOQ | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Salicylic Acid (SA) characterized by t1/2 |  | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Salicylic Acid (SA) characterized by t lag | t lag : Lag-time (time delay between drug administration and first observed concentration above LLOQ | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Salicylic Acid (SA) characterized by Cmax/AUC0-∞ |  | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Salicylic Acid (SA) characterized by MRT | MRT :Mean residence time (for extravascular and iv bolus administration) | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Acetylsalicylic Acid (ASA) characterized by AUC0-t /AUC0-∞ |  | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 
| Plasma concentration of Salicylic Acid (SA) characterized by AUC0-t /AUC0-∞ |  | baseline (pre-dose), 5, 7.5, 10, 12.5, 15, 17.5, 20, 22.5, 25, 27.5, 30, 32.5, 35, 37.5, 40, 42.5, 45, 50, 55 minutes and 1, 1.25, 1.5, 1.75, 2, 3, 4, 5, 7, 9, 12 and 24 hours post-dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events as measure of safety and tolerability |  | Up to 5 weeks |