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
Overview
- Phase
- Phase 1
- Intervention
- single dose (100 mg) of ASA
- Conditions
- Obstructive Pulmonary Function
- Sponsor
- Vectura, Inc.
- Enrollment
- 4
- Locations
- 4
- Primary Endpoint
- Area under the ASA plasma concentration versus time curve (AUC0-inf)
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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
Investigators
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.
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-
- •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.
Arms & Interventions
Arm 1: I-ASA 100mg, then C-ASA 162mg tablet
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.
Intervention: single dose (100 mg) of ASA
Arm 1: I-ASA 100mg, then C-ASA 162mg tablet
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.
Intervention: single dose (162 mg) of non-enteric-coated chewable aspirin tablets
Arm 2: C-ASA 162mg tablet, then I-ASA 100mg
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: single dose (100 mg) of ASA
Arm 2: C-ASA 162mg tablet, then I-ASA 100mg
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: single dose (162 mg) of non-enteric-coated chewable aspirin tablets
Outcomes
Primary Outcomes
Area under the ASA plasma concentration versus time curve (AUC0-inf)
Time Frame: pre-dose and 24 hours post-dose
Area under the ASA plasma concentration versus time curve (AUC0-t)
Time Frame: pre-dose and 24 hours post-dose
Peak plasma concentration of ASA (Cmax)
Time Frame: pre-dose and 24 hours post-dose
Secondary Outcomes
- 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-t) of SA.(minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 240, 360, 480, 720)
- 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)
- 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)
- Proportion of subjects achieving significant inhibition of platelet aggregation (<550 Aspirin Reaction Units [ARU])(2 minutes)
- Time to significant reduction in platelet aggregation (<550 ARU)(assessed up to 24 hours post-dose)
- Time to half-maximal % inhibition (suppression) of serum TxB2 (ID-50).(assessed up to 24 hours post-dose)
- Time to maximum % inhibition of serum TxB2.(assessed up to 24 hours post-dose)
- Time to maximum inhibition of platelet aggregation, assessed by VerifyNow Aspirin test.(assessed up to 24 hours post-dose)
- Maximum % CFB in ARU assessed by VerifyNow tests.(assessed up to 24 hours post-dose)
- Maximum % CFB in urinary 11-dehydro-TxB2.(assessed up to 24 hours post-dose)
- Maximum % CFB in serum 6-keto-PGF1α levels.(assessed up to 24 hours post-dose)
- Incidence and frequency of adverse events(Screening through the 7-day follow-up period)
- Tmax of plasma concentrations of ASA.(assessed up to 24 hours post-dose)
- 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)