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

NCT04328883 | Completed Phase 1 FDA Drug

• 1 other identifier: InovaHCS
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Platelet Aggregation Inhibitors

Outcome Measures

Primary Outcomes (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.

  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.

  24 hours

Secondary Outcomes (8)

• Compare the onset and extent of the pharmacodynamic effect of ASA inhalation powder and chewed non-enteric coated aspirin on ADP-induced platelet aggregation.

  24 hours

• Compare the onset and extent of the pharmacodynamic effect of ASA inhalation powder and chewed non-enteric coated aspirin on Collagen-induced platelet aggregation.

  24 hours

• 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).

  24 hours

• Compare the onset and extent of the pharmacodynamic effect of ASA inhalation powder and chewed non-enteric coated aspirin on 6-keto- PGI1α.

  24 hours

• Compare the extent of the pharmacodynamic effect of ASA inhalation powder and chewed non-enteric coated aspirin on urinary 11-dehydro TxB2.

  24 hours

Study Arms (3)

162 mg Non-Enteric-Coated Chewable aspirin

ACTIVE COMPARATOR

Non-enteric coated aspirin (162mg, single dose)

Drug: Aspirin

50 mg ASA inhalation powder

EXPERIMENTAL

Dry powder inhaled aspirin (50mg,1 dry powder inhalation capsule using dry powder inhaler, single dose)

Drug: Aspirin

100 mg ASA inhalation powder

EXPERIMENTAL

Dry powder inhaled aspirin (100mg,1 dry powder inhalation capsule using dry powder inhaler, single dose)

Drug: Aspirin

Interventions

Aspirin DRUG

Oral and inhaled ASA formulations

Also known as: Bayer Aspirin

100 mg ASA inhalation powder; 162 mg Non-Enteric-Coated Chewable aspirin; 50 mg ASA inhalation powder

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Inova Health Care Services: lead

Study Sites (1)

Inova Fairfax Hospital

Falls Church, Virginia, 22042, United States

Location

Related Publications (1)

• Gurbel PA, Bliden KP, Tantry US. Defining platelet response to acetylsalicylic acid: the relation between inhibition of serum thromboxane B2 and agonist-induced platelet aggregation. J Thromb Thrombolysis. 2021 Feb;51(2):260-264. doi: 10.1007/s11239-020-02334-x. Epub 2020 Nov 10.

  PMID: 33170486 DERIVED

MeSH Terms

Interventions

Aspirin

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Design

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

Study Record Dates

• First Submitted: December 9, 2019
• First Posted: April 1, 2020
• Study Start: July 16, 2019
• Primary Completion: October 3, 2019
• Study Completion: October 10, 2019
• Last Updated: April 1, 2020

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)