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

NCT05625347 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: BORA-1A-C302
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 4

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.

Conditions

Obstructive Pulmonary Function; Restrictive Pulmonary Function

Keywords

ASA; acetylsalicylic acid; cyclooxygenase-1 enzyme; COPD; oral inhalation; inhaled; myocardial Infarction

Outcome Measures

Primary Outcomes (3)

• Peak plasma concentration of ASA (Cmax)

  pre-dose and 24 hours post-dose

• Area under the ASA plasma concentration versus time curve (AUC0-inf)

  pre-dose and 24 hours post-dose

• Area under the ASA plasma concentration versus time curve (AUC0-t)

  pre-dose and 24 hours post-dose

Secondary Outcomes (17)

• Tmax of plasma concentrations of ASA.

  assessed up to 24 hours post-dose

• Tmax of plasma concentrations of SA.

  assessed up to 24 hours post-dose

• Peak Plasma Concentration (Cmax) of SA.

  minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 240, 360, 480, 720

• Area under the plasma concentration versus time curve (AUC0-inf) of SA.

  minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 240, 360, 480, 720

• Area under the plasma concentration versus time curve (AUC0-t) of SA.

  minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 240, 360, 480, 720

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: single dose (100 mg) of ASA; Drug: single dose (162 mg) of non-enteric-coated chewable aspirin tablets

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

EXPERIMENTAL

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.

Drug: single dose (100 mg) of ASA; Drug: single dose (162 mg) of non-enteric-coated chewable aspirin tablets

Interventions

single dose (100 mg) of ASA DRUG

powder for oral inhalation via a Dry Powder Inhaler (DPI)

Arm 1: I-ASA 100mg, then C-ASA 162mg tablet; Arm 2: C-ASA 162mg tablet, then I-ASA 100mg

single dose (162 mg) of non-enteric-coated chewable aspirin tablets DRUG

orally administered

Arm 1: I-ASA 100mg, then C-ASA 162mg tablet; Arm 2: C-ASA 162mg tablet, then I-ASA 100mg

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Non-symptomatic subject on stable uninterrupted maintenance COPD therapy, such that, in the judgement of the Investigator, on the day of dosing in each period, it would be safe to withhold the morning dose of the maintenance treatment until 2 hours post-dose and to withhold PRN short acting rescue bronchodilators from 1 hour pre-dose until 2 hours post-dose.
• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vectura, Inc.: lead
• Syneos Health: collaborator

Study Sites (4)

Omega Research Orlando, LLC

Orlando, Florida, 32808, United States

Location

Clinical Site Partners, LLC CSP Orlando

Winter Park, Florida, 32789, United States

Location

Sinai Hospital

Baltimore, Maryland, 21209, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Respiratory Aspiration; Myocardial Infarction

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiration Disorders; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Necrosis

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: November 22, 2022
• Study Start: March 11, 2023
• Primary Completion: June 30, 2023
• Study Completion: June 30, 2023
• Last Updated: March 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)