A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Smartech Topical Aspirin Gel Formulation Following Multiple Applications in Healthy Adult Volunteers Compared to Oral Aspirin

Exclusion Criteria33

• Participants are excluded from the study if any of the following apply:
• Participant has a platelet aggregation result at screening demonstrating unresponsiveness to AA (defined as less than 60% aggregation).
• Note: If a participant’s screening assessment indicates a platelet aggregation response to AA that is less than 60% (indicating recent aspirin use), the participant may be re-tested once, at the Investigator’s discretion, after abstaining from the use of aspirin and products containing salicylic acid, including dietary or herbal supplements containing salicylates, and from use of NSAIDs, and any antiplatelet or anticoagulant agent for a minimum of 14 days (2 weeks) or 5 half-lives (whichever is longer). If a participant’s platelet aggregation remains unresponsive to AA (defined as less than 60% of aggregation upon repeat testing) the participant will not be eligible for study participation.
• Participant has a history of asthma (resolved childhood asthma acceptable), rhinitis, nasalpolyps, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs.
• Participant has evidence of uncontrolled, clinically significant neurologic (including seizure disorders), cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, or endocrine disease, psychiatric disorder, laboratory abnormality, allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing) that may increase the risksassociated with study participation or in the Investigator’s judgment, make the participant inappropriate for the study. It is the responsibility of the Investigator to assess the clinical significance; however, consultation with the MM may be warranted.
• The participant has a medical history or positive blood test at screening for human immunodeficiency virus (HIV) (anti-HIV1 and anti-HIV2 antibodies), hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody (HCVAb).
• Note: Participants who demonstrate positive HCV serology but return a negative polymerase chain reaction (PCR) follow-up test (i.e., false positive) may be eligible for study participation, at the discretion of the Investigator, and if they meet all other study eligibility criteria.
• Participant has risk factors for cardiovascular thrombotic events, known cardiovascular disease or risk factors for cardiovascular disease.
• Participant has had coronary artery bypass graft surgery within the past 12 months.
• The participant has a history of and/or risk factors for serious gastrointestinal events including peptic ulcer disease and/or gastrointestinal tract bleeding (cholecystectomy and Gilbert’s Syndrome acceptable) that, in the opinion of the Investigator, may compromise the safety of the participant.
• The participant has a history of gastric bypass surgery.
• Acute disease state (unstable medical condition such as nausea, vomiting, fever or diarrhea) within 7 days of admission to the CRU on Day -1.
• Use of systemic/topical corticosteroids within 3 weeks prior to the start of the planned first dose of study drug administration and/or during the study.
• Participant has a diagnosed bleeding disorder (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with blood draws or is unable to provide a blood sample without undue
• trauma or distress or has poor peripheral venous access and is unsuitable for cannulation or repeated venipuncture.
• Platelet count less than 150 x 106/µL.
• Estimated glomerular filtration rate (eGFR) less than 80 mL/min as per the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
• Gamma glutamyl transferase (GGT), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5x the upper limit of normal (ULN). Participants with ALP and/or ALT/AST >1.5x the ULN may be included, at the discretion of the Investigator (or qualified designee), if the levels are unaccompanied by clinical signs and are determined to be normal variants. Liver function tests >1.5x the ULN for bilirubin (total) are exclusionary for this study.
• Loss or donation of whole blood (>499 mL) within 3 months and/or plasma donation within 2 weeks, prior to dosing with the study drug, or intention to donate blood or blood products during the study.
• Use of tobacco or nicotine products exceeding 5 cigarettes (or equivalent) per week in any form within 30 days prior to treatment with the study drug, or unwillingness to refrain from smoking, vaping, or using any nicotine products for at least 48 hours prior to dosing with the study drug, during the confinement period/s, and any follow-up visits.
• History of substance abuse within 3 months prior to screening and/or a positive drug or alcohol screen. A positive drug or alcohol screen test result may be verified by re-testing (up to 1 false positive result permitted) at the discretion of the Investigator (or qualified designee).
• History of excessive regular alcohol consumption within 6 months of screening defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 10 g of alcohol and the following can be used as a guide: a half-pint (~240 ml) of beer, 1 glass (125 mL) of wine or 1 (30 mL) measure of spirits.
• Participation in a clinical trial and receipt of an investigational medication within 30 days, 5 half-lives (if known) or twice the duration of the biological effect of any medication, whichever is longer, prior to the first dose of study drug.
• For WOCBP, a positive serum pregnancy test at screening or a positive urine pregnancy test (with confirmatory serum pregnancy test) at admission (Day -1).
• The participant is planning to become pregnant within 90 days of the study or is breastfeeding.
• Major surgery within 4 weeks of screening that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the participant in the opinion of the Investigator (or qualified
• designee). Any participants who have elective surgical procedures scheduled to occur over the duration of the study and for up to 14 days (2 weeks) following final dosing.
• The participant is unwilling or unable to follow protocol requirements and attendance at follow-up visit(s), or otherwise unsuitable for study participation in the opinion of the Investigator.
• Smartech Topical Aspirin or Vehicle Cohorts Only
• Participants who have a history of or have active forms of dermatitides/eczematous conditions (e.g., contact dermatitis, seborrhhoeic, discoid, gravitational, asteatotic and
• dishydrotic eczema) or other inflammatory skin diseases (e.g., psoriasis, viral infection, fungal infection, bacterial infection), extremely dry skin at the site of application (defined as skin which may be red, scaly, itchy or painful), or any visible skin damage or skin condition (e.g., sunburn, uneven skin tones, tattoos, scars, excessive hair, numerous freckles, or other disfigurations) in or around the intended application site which, in the
• opinion of the Investigator, may interfere with evaluation for skin reactions.
• Unwilling or unable to refrain from the use of sunscreens, cosmetics, creams, ointments, lotions or any other topical products in the intended site of study treatment application for the duration of the study. The use of tanning products or tanning salons is not permitted within 14 days of CRU admission (Day -1) and for the duration of the study.