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

Primary Purpose

Healthy Volunteers

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ASA
non-enteric-coated chewable aspirin
Sponsored by
Vectura, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Healthy Volunteers focused on measuring ASA, acetylsalicylic acid, cyclooxygenase-1 enzyme, oral inhalation, inhaled, myocardial Infarction

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Sinai Hospital
  • Bio-Kinetic Clinical Applications, LLC dba QPS-MO

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm 1: I-ASA 100mg, then C-ASA 162mg tablet

Arm 2: C-ASA 162mg tablet, then I-ASA 100mg

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

Serum thromboxane B2 (TxB2) serum concentration - Area under the effect curve (AUEC) of the % Change from baseline (CFB) in serum TxB2 concentration (TxB2 suppression)

Secondary Outcome Measures

Proportion of subjects achieving significant inhibition of platelet aggregation (<550 Aspirin Reaction Units [ARU])
TxB2 serum concentration - AUEC of the % CFB in serum TxB2 concentration (TxB2 suppression)
TxB2 serum concentration - AUEC of the % CFB in serum TxB2 concentration (TxB2 suppression)
Time to significant inhibition of platelet aggregation (<550 ARU).
Peak plasma concentrations (Cmax) of ASA
PK endpoints
Peak plasma concentrations (Cmax) of SA
PK endpoints
Area under the plasma concentration versus time curve (AUC0-inf)
PK endpoints
Area under the plasma concentration versus time curve (AUC0-t)
PK endpoints
Time to peak plasma concentrations (Tmax) of ASA
PK endpoints
Time to peak plasma concentrations (Tmax) of SA
PK endpoints
Incidence and frequency of Adverse Events.

Full Information

First Posted
November 1, 2022
Last Updated
May 11, 2023
Sponsor
Vectura, Inc.
Collaborators
Syneos Health
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1. Study Identification

Unique Protocol Identification Number
NCT05625334
Brief Title
Study to Compare the Pharmacodynamics and Pharmacokinetics of Acetylsalicylic Acid Powder for Oral Inhalation With Non-enteric-coated Chewable Aspirin in Healthy Adults.
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
October 14, 2022 (Actual)
Primary Completion Date
March 9, 2023 (Actual)
Study Completion Date
March 9, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vectura, Inc.
Collaborators
Syneos Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy Volunteers
Keywords
ASA, acetylsalicylic acid, cyclooxygenase-1 enzyme, oral inhalation, inhaled, myocardial Infarction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
86 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1: I-ASA 100mg, then C-ASA 162mg tablet
Arm Type
Experimental
Arm Description
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).
Arm Title
Arm 2: C-ASA 162mg tablet, then I-ASA 100mg
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ASA
Intervention Description
powder for oral inhalation via a Dry Powder Inhaler (DPI)
Intervention Type
Drug
Intervention Name(s)
non-enteric-coated chewable aspirin
Intervention Description
Orally administered
Primary Outcome Measure Information:
Title
Serum thromboxane B2 (TxB2) serum concentration - Area under the effect curve (AUEC) of the % Change from baseline (CFB) in serum TxB2 concentration (TxB2 suppression)
Time Frame
24 hours post-dose
Secondary Outcome Measure Information:
Title
Proportion of subjects achieving significant inhibition of platelet aggregation (<550 Aspirin Reaction Units [ARU])
Time Frame
2 minutes post-dose
Title
TxB2 serum concentration - AUEC of the % CFB in serum TxB2 concentration (TxB2 suppression)
Time Frame
20 minutes post-dose.
Title
TxB2 serum concentration - AUEC of the % CFB in serum TxB2 concentration (TxB2 suppression)
Time Frame
30 minutes post-dose
Title
Time to significant inhibition of platelet aggregation (<550 ARU).
Time Frame
assessed up to 24 hours post-dose
Title
Peak plasma concentrations (Cmax) of ASA
Description
PK endpoints
Time Frame
pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
Title
Peak plasma concentrations (Cmax) of SA
Description
PK endpoints
Time Frame
pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
Title
Area under the plasma concentration versus time curve (AUC0-inf)
Description
PK endpoints
Time Frame
pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
Title
Area under the plasma concentration versus time curve (AUC0-t)
Description
PK endpoints
Time Frame
pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
Title
Time to peak plasma concentrations (Tmax) of ASA
Description
PK endpoints
Time Frame
pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
Title
Time to peak plasma concentrations (Tmax) of SA
Description
PK endpoints
Time Frame
pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
Title
Incidence and frequency of Adverse Events.
Time Frame
screening through the 7-day to follow-up period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Facility Information:
Facility Name
Sinai Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21215
Country
United States
Facility Name
Bio-Kinetic Clinical Applications, LLC dba QPS-MO
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65802
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32986482
Citation
Gurbel PA, Bliden KP, Chaudhary R, Tantry US. First In-Human Experience With Inhaled Acetylsalicylic Acid for Immediate Platelet Inhibition: Comparison With Chewed and Swallowed Acetylsalicylic Acid. Circulation. 2020 Sep 29;142(13):1305-1307. doi: 10.1161/CIRCULATIONAHA.120.047477. Epub 2020 Sep 28. No abstract available.
Results Reference
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Study to Compare the Pharmacodynamics and Pharmacokinetics of Acetylsalicylic Acid Powder for Oral Inhalation With Non-enteric-coated Chewable Aspirin in Healthy Adults.

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