Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Pharmacodynamics and Pharmacokinetics of Aspirin Inhalation Powder With Non-Enteric-Coated Chewable Aspirin

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04328883
Recruitment Status : Completed
First Posted : April 1, 2020
Last Update Posted : April 1, 2020
Sponsor:
Information provided by (Responsible Party):
Inova Health Care Services

Brief Summary:

ASA inhalation powder is an inhaled nonsteroidal anti-inflammatory drug-device combination that has been developed to reduce the risk of vascular mortality in patients with suspected acute myocardial infarction (MI), an FDA approved indication for oral formulations of aspirin.

The primary goal of study OTP-P0-926 is to collect pharmacokinetic (PK)and pharmacodynamics (PD) pilot data to determine onset and extent of aspirin response after administration of varying doses of inhaled ASA (50-100mg) and 162 mg Non-Enteric-Coated Chewable ASA. PD will be assessed using standard methods to measure platelet inhibition by aspirin including platelet aggregation, serum thromboxane,and urinary thromboxane. Furthermore, the pharmacokinetics (PK) of ASA will be determined and compared to PD measurements. Results of this pilot study will guide dosing in a subsequent larger Phase II study.


Condition or disease Intervention/treatment Phase
Platelet Aggregation Inhibitors Drug: Aspirin Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Single-dose, Open-label, Pilot Study to Compare the Pharmacodynamics and Pharmacokinetics of Acetylsalicylic Acid Inhalation Powder With Non-Enteric-Coated Chewable Aspirin in Healthy Adults
Actual Study Start Date : July 16, 2019
Actual Primary Completion Date : October 3, 2019
Actual Study Completion Date : October 10, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
Active Comparator: 162 mg Non-Enteric-Coated Chewable aspirin
Non-enteric coated aspirin (162mg, single dose)
Drug: Aspirin
Oral and inhaled ASA formulations
Other Name: Bayer Aspirin

Experimental: 50 mg ASA inhalation powder
Dry powder inhaled aspirin (50mg,1 dry powder inhalation capsule using dry powder inhaler, single dose)
Drug: Aspirin
Oral and inhaled ASA formulations
Other Name: Bayer Aspirin

Experimental: 100 mg ASA inhalation powder
Dry powder inhaled aspirin (100mg,1 dry powder inhalation capsule using dry powder inhaler, single dose)
Drug: Aspirin
Oral and inhaled ASA formulations
Other Name: Bayer Aspirin




Primary Outcome Measures :
  1. Compare the onset and extent of the pharmacodynamic effect of ASA inhalation powder (50-100 mg) and chewed non-enteric coated aspirin (162 mg) on arachidonic acid (AA)-induced platelet aggregation. [ Time Frame: 24 hours ]
    Change from pre-dose in 1mM arachidonic-induced platelet aggregations at 2, 5, 10, 20,30, 40 minutes and 1,4, and 24hours after dosing with 50, 100mg aspirin dry powder inhalation and 162mg chewed non-enteric coated aspirin.


Secondary Outcome Measures :
  1. Compare the onset and extent of the pharmacodynamic effect of ASA inhalation powder and chewed non-enteric coated aspirin on ADP-induced platelet aggregation. [ Time Frame: 24 hours ]
    Change from pre-dose on 5uM ADP-induced platelet aggregation at 2, 5, 10, 20,30, 40 minutes and 1,4, and 24hours after dosing with 50, 100mg aspirin dry powder inhalation and 162mg chewed non-enteric coated aspirin.

  2. Compare the onset and extent of the pharmacodynamic effect of ASA inhalation powder and chewed non-enteric coated aspirin on Collagen-induced platelet aggregation. [ Time Frame: 24 hours ]
    Change from pre-dose on 4ug Collagen-induced platelet aggregation at 2, 5, 10, 20,30, 40 minutes and 1,4, and 24hours after dosing with 50, 100mg aspirin dry powder inhalation and 162mg chewed non-enteric coated aspirin.

  3. Compare the onset and extent of the pharmacodynamic effect of ASA inhalation powder and chewed non-enteric coated aspirin on serum concentrations of thromboxane B2 (TxB2). [ Time Frame: 24 hours ]
    Change from pre-dose on serum concentrations of TxB2 at 2, 5, 10, 20,30, 40 minutes and 1,4, and 24hours after dosing with 50, 100mg aspirin dry powder inhalation and 162mg chewed non-enteric coated aspirin.

  4. Compare the onset and extent of the pharmacodynamic effect of ASA inhalation powder and chewed non-enteric coated aspirin on 6-keto- PGI1α. [ Time Frame: 24 hours ]
    Change from pre-dose on 6-keto- PGI1α at 2, 5, 10, 20,30, 40 minutes and 1,4, and 24hours after dosing with 50, 100mg aspirin dry powder inhalation and 162mg chewed non-enteric coated aspirin.

  5. Compare the extent of the pharmacodynamic effect of ASA inhalation powder and chewed non-enteric coated aspirin on urinary 11-dehydro TxB2. [ Time Frame: 24 hours ]
    Change from pre-dose on urinary 11-dehydro TxB2 at 4, and 24 hours after dosing with 50, 100mg aspirin dry powder inhalation and 162mg chewed non-enteric coated aspirin.

  6. Compare the time to maximum drug concentration (Tmax) on ASA and salicylic acid (SA) pharmacokinetics following single doses of ASA inhalation powder and oral (Non-Enteric-Coated Chewable ) aspirin [ Time Frame: 24 hours ]
    Compare Tmax between treatment groups

  7. Compare the maximum drug concentration (Cmax) on ASA and salicylic acid (SA) pharmacokinetics following single doses of ASA inhalation powder and oral (Non-Enteric-Coated Chewable ) aspirin [ Time Frame: 24 hours ]
    Compare Cmax between treatment groups

  8. Evaluate change in forced expiratory-1 (FEV-1) after a single dose of acetylsalicylic acid (ASA) inhalation powder administered as ASA inhalation powder [ Time Frame: 24 hours ]
    Evaluate change in forced expiratory-1 (FEV-1) from pre-dose measures after a single dose of acetylsalicylic acid (ASA) inhalation powder administered as ASA inhalation after 4 and 24hours post dosing.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female subjects, 18-55 years of age
  • Non-smokers
  • Body mass index (BMI) within 18.5 kg/m2 to 32.0 kg/m2
  • Female subjects of childbearing potential must agree to use acceptable methods of birth control or abstain from sex during study participation and must have a negative serum or urine pregnancy test
  • Subjects must be healthy as determined by medical history, physical examination, vital signs, and clinical laboratory evaluation
  • Signed informed consent

Exclusion Criteria:

  • At screening visit, subjects with a forced expiratory volume in 1 second (FEV1) (i.e., FEV1% predicted < 80%).
  • At screening visit, subjects with a forced expiratory flow at 25%-75% (FEF 25%-75%) of pulmonary volume < 70% predicted.
  • Patients with a flow rate <70 L/min with a G-16 training device set at medium resistance.
  • Hematocrit value ≤32%
  • Clinically significant hemoglobin value, at screening, as per investigator.
  • Arachidonic acid induced-maximum platelet aggregation <50%.
  • Platelet count <142,000 or > 450,000 µL.
  • Presence of any tongue piercings or history of any tongue piercings in the last 90 days prior to the first study drug administration.
  • Presence of braces, partials or dentures.
  • Clinically significant abnormal laboratory parameters.
  • Antiplatelet agents (ASA, NSAID's, P2Y12 inhibitors, etc.) within 10 days of dosing visit.
  • HIV, hepatitis B or C infection.
  • Presence of clinically significant cardiovascular, pulmonary, hepatic, renal, endocrinological, hematological, immunologic, metabolic, neurological, or gastrointestinal disease.
  • Clinically significant physical examination.
  • History of hypersensitivity or allergy to aspirin.
  • History of significant bleeding disorders.
  • History of peptic ulcer disease.
  • History of asthma or chronic obstructive pulmonary disease.
  • Concurrent corticosteroid use with the exception of topical; any previous use must have occurred at least 90 days prior to Day 1 of the study and be approved by the Investigator.
  • Administration of any prescription/over the counter medications/herbal/nutritional supplements within 14 days that has an effect on platelets prior to visit1 of the study.
  • Administration of any investigational drug product (IP) within 30 days prior to visit 1.
  • ALT ≥ 3xULN.
  • Total Bilirubin > 1.5x ULN (isolated bilirubin > 1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin < 35%).
  • Donation of blood or platelets within 60 days prior to visit 1.
  • Any condition, illness, or disease that in the opinion of the investigator would interfere with the subject's ability to comply with the requirements of this protocol.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04328883


Locations
Layout table for location information
United States, Virginia
Inova Fairfax Hospital
Falls Church, Virginia, United States, 22042
Sponsors and Collaborators
Inova Health Care Services
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Inova Health Care Services
ClinicalTrials.gov Identifier: NCT04328883    
Other Study ID Numbers: InovaHCS
First Posted: April 1, 2020    Key Record Dates
Last Update Posted: April 1, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Respiratory Aspiration
Respiration Disorders
Respiratory Tract Diseases
Pathologic Processes
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics