An Open-label, Single Ascending Dose Study of the Safety, Tolerability, and Pharmacokinetics of LYN-163 in Healthy Volunteers

Exclusion Criteria58

• Individuals with known clinically significant esophageal or GI disease, including but not limited to:
• a. Known strictures such as esophageal web, pyloric stenosis, or small intestinal stricture, or individuals with high risk of stricture, i.e., Crohn's disease.
• b. Diagnosis of a condition known to elevate or lower gastric pH, e.g., achlorhydria or hypochlorhydria.
• c. Prior varices or small or large bowel obstructions.
• d. Prior abdominal or upper gastrointestinal surgery. (Prior uncomplicated laparoscopic procedures are permitted.)
• e. History of dysphagia or aspiration in the last 5 years.
• f. History of an esophageal motility disorder or undergoing treatment for a gastric motility disorder.
• g. Multiple episodes of abdominal pain in the prior 3 months.
• h. Moderate or severe dysmenorrhea or menorrhagia (with use of pain medication) in the prior 3 months.
• History of moderate to severe Acid Reflux Disease or a score of greater than or equal to 2 on the Acid Reflux Severity Scale (ARSS), indicating moderate to severe symptoms. The ARSS scale is as follows:
• None = 0 no symptoms.
• Mild = 1 awareness of symptom, but easily tolerated.
• Moderate = 2 discomfort sufficient to cause interference with normal activities.
• Severe = 3 incapacitating, with inability to perform normal activities.
• Individuals with PILL-5 questionnaire score of 5 or greater.
• Medical history or current diagnoses indicating the presence of any of the following conditions:
• a. Presence of an uncontrolled, unstable, clinically significant medical condition that could put the participant at risk because of participation in the study, interfere with the participant’s ability to participate in the study or influence the interpretation of safety or PK evaluations.
• b. History of a major cardiovascular event (myocardial infarction, cardiac surgery or revascularization, unstable angina, stroke, or transient ischemic attack) or a hospitalization forheart failure within 6 months of Screening.
• c. Any clinically significant illness, medical or surgical procedure, or trauma within 4weeks of Screening.
• d. Known immunocompromised status, including individuals who have undergone organ transplantation, on immunosuppression therapy for an immune mediated disease, or are positive for human immunodeficiency virus (HIV).
• e. Positive test for active hepatitis B or C at Screening. Individuals with successfully treated hepatitis B infection which has been resolved for greater than 1 year or successfully treated hepatitis C infection will not be excluded.
• f. Donated more than 250 mL of blood within 4 weeks of Screening.
• g. Difficulties with venipuncture/cannulation, including difficulty accessing veins for blood sampling and/or history of coagulopathy or endocarditis.
• h. Active SARS-CoV-2 infection
• Use of the following medications/treatments in the 2 weeks before enrollment, including:
• a. Warfarin.
• b. Proton pump inhibitors.
• c. H2 blockers.
• d. Prokinetic agents.
• e. Concomitant medications, natural remedies, supplements, or vitamins. Use of antacids is permissible, except within 2 hours of dosing with LYN-163.
• f. Non-steroidal anti-inflammatory drugs or acetylsalicylic acid.
• g. Medications that may interfere with the absorption, metabolism, or excretion of ivermectin.
• h. Hormonal contraceptives.
• Use of blood products within 3 months of Screening.
• Clinically significant abnormal safety (e.g.,physical examination, vital signs) or laboratory assessments at Screening, specifically:
• a. Presence of a clinically significant abnormal laboratory result on blood or urine safety tests.
• b. Anemia (hemoglobin below the lower limit of normal reference range).
• c. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) greater than or equal to 3.0 × the upper limit of normal (ULN), or total bilirubin greater than or equal to 1.5 × ULN.
• d. Moderate or severe renal insufficiency (glomerular filtration rate <60mL/min, as determined using the Cockcroft-Gault formula).
• e. Heart rate of <50 beats per minute (bpm).
• f. Systolic blood pressure greater than or equal to 150 and/or diastolic blood pressure greater than or equal to 100mmHg.
• g. Diabetes or HbA1c greater than or equal to 7.0 % at Screening.
• h. Positive fecal occult blood test at Screening.
• i. Thrombocytopenia (platelet count <150×109/L) or bleeding diathesis (INR >1.4) at Screening.
• j. Creatine kinase >3 × ULN.
• History of any drug or alcohol use disorder in the past 2years. Positive results for drugs of abuse or positive ethanol breathalyzer screen finding will exclude individuals unless the positive finding can be accounted for by documented prescription use. Exclusions include:
• a. History of alcohol consumption exceeding moderate use; in males exceeding 21units per week and in females exceeding 14 units per week (1 unit is equal to 360 ml beer, 25 mL of 40% spirit or a 125 mL glass of wine) over the past month. Participants are not permitted to consume alcohol during the inpatient stay nor 12 hours before any clinic visit while an outpatient.
• b. Current smokers, users of e-cigarettes, vaping products, or nicotine replacement products and individuals who have smoked within the last 12months. Positive results for cotinine are exclusionary.
• Individuals of reproductive potential who are (hetero) sexually active but unwilling to use acceptable means of contraception through the EOS. For clarity, individuals who are at least 1 year post-menopausal are not of reproductive potential. Acceptable means of contraception include:
• a. Individuals who have been surgically sterilized.
• b. Females of reproductive potential: diaphragm, contraceptive sponge, or intrauterine device in use before enrollment.
• c. Males: condom in combination with any of the above means of contraception for their female partners.
• d. All individuals: abstinence.
• Individuals who are nursing or who have a positive or indeterminate pregnancy test at either Screening (serum test) or enrollment (urine test).
• Use of any experimental agent within 3 months or 5 half-lives of Screening, whichever is longer.
• Employees or immediate family members of employees of the site, Sponsor, or study-related vendors.
• History of hypersensitivity to LYN-163 components (ivermectin and excipients).
• Individuals with history of X-ray, computed tomography scan,or angiogram of the abdomen within one year of Screening.