Clinical trial NCT05625334: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: ASA
acetylsalicylic acid
cyclooxygenase-1 enzyme
oral inhalation
inhaled
myocardial Infarction
Lead sponsor: Vectura, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2022-11-22
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Healthy as defined by:

   1. the absence of clinically significant illness and surgery within 4 weeks prior to dosing.
   2. 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.
3. Female subjects of non-childbearing potential must be:

   1. post-menopausal OR
   2. surgically sterile at least 3 months prior to dosing.
4. Sexually active female subjects of childbearing potential must be willing to use an acceptable contraceptive method throughout the study as defined in the protocol.
5. 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.
6. Agrees to refrain from alcohol consumption for at least 48 hours prior to admission and 48 hours after drug administration of each period.
7. Able to understand the study procedures and provide signed informed consent to participate in the study.

Exclusion Criteria:

1. Any clinically significant abnormal finding at physical examination at screening.
2. Positive serology test results for HBsAg, HCV antibody, or HIV antigen and antibody, at screening.
3. Positive pregnancy test or lactating female subject.
4. Positive urine drug screen, urine cotinine test, or alcohol breath test.
5. Known allergic reactions, hypersensitivity or contraindications to aspirin (ASA), ibuprofen, other NSAIDs, or other related drugs, or to any excipient in the formulation.
6. Known lack of response (lack of effect) to aspirin in the past.
7. Clinically significant x-ray, ECG abnormalities or vital signs abnormalities at screening.
8. Clinically significant abnormal laboratory parameters including:

   1. Hematocrit value ≤ 32%;
   2. Platelet count \<142,000 or \> 450,000 platelets per µL;
   3. ALT ≥ 3 x ULN;
   4. AST ≥ 3 x ULN.
9. 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.
10. 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.

Primary outcomes:
measure: Serum thromboxane B2 (TxB2) serum concentration - Area under the effect curve (AUEC) of the % Change from baseline (CFB) in serum TxB2 concentration (TxB2 suppression)
timeFrame: 24 hours post-dose
Secondary outcomes:
measure: Proportion of subjects achieving significant inhibition of platelet aggregation (<550 Aspirin Reaction Units [ARU])
timeFrame: 2 minutes post-dose
measure: TxB2 serum concentration - AUEC of the % CFB in serum TxB2 concentration (TxB2 suppression)
timeFrame: 20 minutes post-dose.
measure: TxB2 serum concentration - AUEC of the % CFB in serum TxB2 concentration (TxB2 suppression)
timeFrame: 30 minutes post-dose
measure: Time to significant inhibition of platelet aggregation (<550 ARU).
timeFrame: assessed up to 24 hours post-dose
measure: Peak plasma concentrations (Cmax) of ASA
timeFrame: pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
measure: Peak plasma concentrations (Cmax) of SA
timeFrame: pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
measure: Area under the plasma concentration versus time curve (AUC0-inf)
timeFrame: pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
measure: Area under the plasma concentration versus time curve (AUC0-t)
timeFrame: pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
measure: Time to peak plasma concentrations (Tmax) of ASA
timeFrame: pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
measure: Time to peak plasma concentrations (Tmax) of SA
timeFrame: pre-dose. minutes post-dose: 2, 5, 10, 20, 30, 45, 60, 120, 180, 360, 480, 720 and 1440
measure: Incidence and frequency of Adverse Events.
timeFrame: screening through the 7-day to follow-up period
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Sinai Hospital
state: Maryland
city: Springfield
country: United States
facility: Bio-Kinetic Clinical Applications, LLC dba QPS-MO
state: Missouri
Study officials:
References:
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.