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Study to Compare the Pharmacokinetics and Pharmacodynamics of ASA Powder for Oral Inhalation With Non-enteric-coated Chewable Aspirin in Adult Subjects With Obstructive or Restrictive Pulmonary Function

Primary Purpose

Obstructive Pulmonary Function, Restrictive Pulmonary Function

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
single dose (100 mg) of ASA
single dose (162 mg) of non-enteric-coated chewable aspirin tablets
Sponsored by
Vectura, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Obstructive Pulmonary Function focused on measuring ASA, acetylsalicylic acid, cyclooxygenase-1 enzyme, COPD, oral inhalation, inhaled, myocardial Infarction

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: All Cohorts Subjects must meet all of the following criteria to be included in the study: Male or female, ≥ 40 years of age. BMI >18.0 and <35.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females. Clinically stable as determined by medical history, physical examination, vital signs, and clinical laboratory evaluation. Female subjects of non-childbearing potential must be: post-menopausal; or surgically sterile at least 3 months prior to first dosing. Sexually active female subjects of childbearing potential must be willing to use an acceptable contraceptive method throughout the study as detailed in protocol. Smoker (no more than 25 cigarettes or equivalent daily) or non-smoker. Obstructive Pulmonary Function Cohort Subject with a smoking history of at least 10 pack-years. Subject with an established diagnosis of COPD at least 12 months prior to the screening visit AND confirmed at screening by spirometry, with a post bronchodilator FEV1 greater than 40% and equal to or less than 70% of the subject's normal predicted value and a post-bronchodilator FEV1 greater than 40% and equal to or less than 70% of the subject's normal predicted value and a post-bronchodilator FEV1/ FVC ratio < 0.70. Subject on stable uninterrupted maintenance COPD therapy for at least 3 months prior to screening as per SoC and without any history of moderate or severe exacerbations within 6 months prior to screening. Restrictive Pulmonary Function Cohort Subject with a history and documented prior diagnosis of underlying chronic respiratory or cardiac disease with restrictive pulmonary function as confirmed at the screening visit by: FEV1/FVC ≥ 0. 7 and FVC < LLN (or < 80% predicted) and TLC < 5th percentile predicted (or < 80% predicted) and DLCO ≤ 75% to ≥ 35% predicted Continued uninterrupted SoC therapy for underlying disease for at least 12 consecutive weeks immediately prior to screening. Exclusion Criteria: All Cohorts: Presence of clinically significant uncontrolled or unstable cardiovascular, pulmonary, hepatic, renal, endocrinological, hematological, immunologic, metabolic, psychological, neurological, or gastrointestinal disease. Any new clinically significant abnormal finding at physical examination at screening. Positive serology test results for HBsAg, HCV antibody, or HIV antigen and antibody, or TB test at screening. Positive pregnancy test or lactating female subject. Positive urine drug screen or alcohol breath test. Positive test for active COVID-19. Known allergic reactions, hypersensitivity or contraindications to ASA, ibuprofen, other NSAID, 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 ECG abnormalities or vital signs abnormalities at screening. Clinically significant abnormal laboratory parameters at screening Presence of active or latent tuberculosis. History of asthma, including childhood asthma, syndrome of asthma, rhinitis (including allergic rhinitis), nasal polyps, angioedema, urticaria, angioedema, or bronchospasm that in investigator's opinion is not suitable to participate in the study. Subject with current asthma defined as post-bronchodilator FEV1 > 12% increase AND >200 ml absolute increase from pre-bronchodilator values. History of non-trauma related hemorrhage. Restrictive Pulmonary Function Cohort Subject had lung surgery, with lung removal, as the reason for restrictive pulmonary function. Subject receiving systemic corticosteroid treatment of prednisone > 10 mg/day or equivalent within 3 months of screening. Subject suffers from restrictive pulmonary function, co-existent with obstructive pulmonary function disease. Subject has baseline resting oxygen saturation of < 89% on room air. Subject in need of continuous oxygen use and/or prescribed long-term continuous home oxygen therapy. Other Protocol defined I/E criteria that apply

Sites / Locations

  • Clinical Site Partners, LLC CSP OrlandoRecruiting
  • Sinai HospitalRecruiting
  • Hassman Research InstituteRecruiting

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) tablets.

Treatment A: Single dose of 162 mg chewable non-enteric-coated Aspirin (C-ASA)tablets. Treatment B: Single dose of 100 mg ASA powder for oral inhalation (I-ASA) via DPI.

Outcomes

Primary Outcome Measures

Peak plasma concentration of ASA (Cmax)
Area under the ASA plasma concentration versus time curve (AUC0-inf)
Area under the ASA plasma concentration versus time curve (AUC0-t)

Secondary Outcome Measures

Tmax of plasma concentrations of ASA.
Tmax of plasma concentrations of SA.
Peak Plasma Concentration (Cmax) of SA.
Area under the plasma concentration versus time curve (AUC0-inf) of SA.
Area under the plasma concentration versus time curve (AUC0-t) of SA.
Serum thromboxane B2 (TxB2) serum concentration - Area under the effect curve (AUEC) of the % Change from baseline (CFB) in serum TxB2 concentration (TxB2 suppression).
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)
Proportion of subjects achieving significant inhibition of platelet aggregation (<550 Aspirin Reaction Units [ARU])
Time to significant reduction in platelet aggregation (<550 ARU)
Time to half-maximal % inhibition (suppression) of serum TxB2 (ID-50).
Time to maximum % inhibition of serum TxB2.
Time to maximum inhibition of platelet aggregation, assessed by VerifyNow Aspirin test.
Maximum % CFB in ARU assessed by VerifyNow tests.
Maximum % CFB in urinary 11-dehydro-TxB2.
Maximum % CFB in serum 6-keto-PGF1α levels.
Incidence and frequency of adverse events

Full Information

First Posted
November 1, 2022
Last Updated
April 27, 2023
Sponsor
Vectura, Inc.
Collaborators
Syneos Health
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1. Study Identification

Unique Protocol Identification Number
NCT05625347
Brief Title
Study to Compare the Pharmacokinetics and Pharmacodynamics of ASA Powder for Oral Inhalation With Non-enteric-coated Chewable Aspirin in Adult Subjects With Obstructive or Restrictive Pulmonary Function
Official Title
A Single-dose, Open-label, Multi-center, Randomized, 2-treatment Crossover Study to Compare the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Acetylsalicylic Acid Powder for Oral Inhalation With Non-enteric-coated Chewable Aspirin in Adult Subjects With Obstructive or Restrictive Pulmonary Function
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 11, 2023 (Actual)
Primary Completion Date
July 11, 2023 (Anticipated)
Study Completion Date
July 11, 2023 (Anticipated)

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 pharmacokinetics (PK) pharmacodynamics (PD), safety and tolerability of acetylsalicylic acid powder for oral inhalation (I-ASA) with non-enteric-coated chewable aspirin (C-ASA) in adult subjects with obstructive or restrictive pulmonary function. 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.
Detailed Description
Up to 16 adult males and females subjects are planned for enrollment in this study, to achieve a minimum of 10 subjects with evaluable PD/PK, safety, and tolerability data: 5 subjects with obstructive lung function [i.e., diagnosed with chronic obstructive pulmonary disease (COPD)]; and 5 subjects with restrictive lung function

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obstructive Pulmonary Function, Restrictive Pulmonary Function
Keywords
ASA, acetylsalicylic acid, cyclooxygenase-1 enzyme, COPD, 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
16 (Anticipated)

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) tablets.
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)tablets. Treatment B: Single dose of 100 mg ASA powder for oral inhalation (I-ASA) via DPI.
Intervention Type
Drug
Intervention Name(s)
single dose (100 mg) of ASA
Intervention Description
powder for oral inhalation via a Dry Powder Inhaler (DPI)
Intervention Type
Drug
Intervention Name(s)
single dose (162 mg) of non-enteric-coated chewable aspirin tablets
Intervention Description
orally administered
Primary Outcome Measure Information:
Title
Peak plasma concentration of ASA (Cmax)
Time Frame
pre-dose and 24 hours post-dose
Title
Area under the ASA plasma concentration versus time curve (AUC0-inf)
Time Frame
pre-dose and 24 hours post-dose
Title
Area under the ASA plasma concentration versus time curve (AUC0-t)
Time Frame
pre-dose and 24 hours post-dose
Secondary Outcome Measure Information:
Title
Tmax of plasma concentrations of ASA.
Time Frame
assessed up to 24 hours post-dose
Title
Tmax of plasma concentrations of SA.
Time Frame
assessed up to 24 hours post-dose
Title
Peak Plasma Concentration (Cmax) of SA.
Time Frame
minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 240, 360, 480, 720
Title
Area under the plasma concentration versus time curve (AUC0-inf) of SA.
Time Frame
minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 240, 360, 480, 720
Title
Area under the plasma concentration versus time curve (AUC0-t) of SA.
Time Frame
minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 240, 360, 480, 720
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
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
Proportion of subjects achieving significant inhibition of platelet aggregation (<550 Aspirin Reaction Units [ARU])
Time Frame
2 minutes
Title
Time to significant reduction in platelet aggregation (<550 ARU)
Time Frame
assessed up to 24 hours post-dose
Title
Time to half-maximal % inhibition (suppression) of serum TxB2 (ID-50).
Time Frame
assessed up to 24 hours post-dose
Title
Time to maximum % inhibition of serum TxB2.
Time Frame
assessed up to 24 hours post-dose
Title
Time to maximum inhibition of platelet aggregation, assessed by VerifyNow Aspirin test.
Time Frame
assessed up to 24 hours post-dose
Title
Maximum % CFB in ARU assessed by VerifyNow tests.
Time Frame
assessed up to 24 hours post-dose
Title
Maximum % CFB in urinary 11-dehydro-TxB2.
Time Frame
assessed up to 24 hours post-dose
Title
Maximum % CFB in serum 6-keto-PGF1α levels.
Time Frame
assessed up to 24 hours post-dose
Title
Incidence and frequency of adverse events
Time Frame
Screening through the 7-day follow-up period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All Cohorts Subjects must meet all of the following criteria to be included in the study: Male or female, ≥ 40 years of age. BMI >18.0 and <35.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females. Clinically stable as determined by medical history, physical examination, vital signs, and clinical laboratory evaluation. Female subjects of non-childbearing potential must be: post-menopausal; or surgically sterile at least 3 months prior to first dosing. Sexually active female subjects of childbearing potential must be willing to use an acceptable contraceptive method throughout the study as detailed in protocol. Smoker (no more than 25 cigarettes or equivalent daily) or non-smoker. Obstructive Pulmonary Function Cohort Subject with a smoking history of at least 10 pack-years. Subject with an established diagnosis of COPD at least 12 months prior to the screening visit AND confirmed at screening by spirometry, with a post bronchodilator FEV1 greater than 40% and equal to or less than 70% of the subject's normal predicted value and a post-bronchodilator FEV1 greater than 40% and equal to or less than 70% of the subject's normal predicted value and a post-bronchodilator FEV1/ FVC ratio < 0.70. Subject on stable uninterrupted maintenance COPD therapy for at least 3 months prior to screening as per SoC and without any history of moderate or severe exacerbations within 6 months prior to screening. Restrictive Pulmonary Function Cohort Subject with a history and documented prior diagnosis of underlying chronic respiratory or cardiac disease with restrictive pulmonary function as confirmed at the screening visit by: FEV1/FVC ≥ 0. 7 and FVC < LLN (or < 80% predicted) and TLC < 5th percentile predicted (or < 80% predicted) and DLCO ≤ 75% to ≥ 35% predicted Continued uninterrupted SoC therapy for underlying disease for at least 12 consecutive weeks immediately prior to screening. Exclusion Criteria: All Cohorts: Presence of clinically significant uncontrolled or unstable cardiovascular, pulmonary, hepatic, renal, endocrinological, hematological, immunologic, metabolic, psychological, neurological, or gastrointestinal disease. Any new clinically significant abnormal finding at physical examination at screening. Positive serology test results for HBsAg, HCV antibody, or HIV antigen and antibody, or TB test at screening. Positive pregnancy test or lactating female subject. Positive urine drug screen or alcohol breath test. Positive test for active COVID-19. Known allergic reactions, hypersensitivity or contraindications to ASA, ibuprofen, other NSAID, 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 ECG abnormalities or vital signs abnormalities at screening. Clinically significant abnormal laboratory parameters at screening Presence of active or latent tuberculosis. History of asthma, including childhood asthma, syndrome of asthma, rhinitis (including allergic rhinitis), nasal polyps, angioedema, urticaria, angioedema, or bronchospasm that in investigator's opinion is not suitable to participate in the study. Subject with current asthma defined as post-bronchodilator FEV1 > 12% increase AND >200 ml absolute increase from pre-bronchodilator values. History of non-trauma related hemorrhage. Restrictive Pulmonary Function Cohort Subject had lung surgery, with lung removal, as the reason for restrictive pulmonary function. Subject receiving systemic corticosteroid treatment of prednisone > 10 mg/day or equivalent within 3 months of screening. Subject suffers from restrictive pulmonary function, co-existent with obstructive pulmonary function disease. Subject has baseline resting oxygen saturation of < 89% on room air. Subject in need of continuous oxygen use and/or prescribed long-term continuous home oxygen therapy. Other Protocol defined I/E criteria that apply
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Pankaj Goyal, M.D.
Phone
+41 (58) 242 23 58
Email
Pankaj.Goyal@vecturafertinpharma.com
First Name & Middle Initial & Last Name or Official Title & Degree
Misty D'Ottavio, RN
Phone
(919) 996-0332
Email
misty.dottavio@vecturafertinpharma.com
Facility Information:
Facility Name
Clinical Site Partners, LLC CSP Orlando
City
Winter Park
State/Province
Florida
ZIP/Postal Code
32789
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alison Only
Phone
407-740-8078
Ext
239
Email
aonly@flourishresearch.com
Facility Name
Sinai Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21209
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kevin Bliden
Phone
410-601-1412
Email
kbliden@lifebridgehealth.org
First Name & Middle Initial & Last Name & Degree
Paul Gurbel, M.D.
Facility Name
Hassman Research Institute
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Allen Salm, M.D.
Phone
856-753-7335
Email
a.salm@cenexel.com

12. IPD Sharing Statement

Learn more about this trial

Study to Compare the Pharmacokinetics and Pharmacodynamics of ASA Powder for Oral Inhalation With Non-enteric-coated Chewable Aspirin in Adult Subjects With Obstructive or Restrictive Pulmonary Function

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