A Phase 1, Randomised, Double-Blind Placebo-Controlled, First in Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of ANPA-0073 in Healthy Volunteers

Exclusion Criteria23

• History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past 3 months determined by the PI to be clinically significant
• Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications
• Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma)
• Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia
• Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration
• History of risk factors for torsade de pointes (including a family history of long QT syndrome or sudden cardiac death) or a known arrythmia
• Findings on transthoracic echocardiogram to have LV ejection fraction on less than 50%, more than mild mitral or aortic valvular regurgitation, or more than mild mitral or aortic valvular stenosis
• Liver function test results elevated more than 1.5-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total, conjugated and unconjugated), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants
• Positive test results for active human immunodeficiency virus (HIV-1 or HIV-2), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at the screening visit
• Presence or having sequelae of gastrointestinal, liver (including Gilbert’s syndrome), kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
• Estimated creatinine clearance (CrCl) less than 60 mL/min using the Cockcroft-Gault formula or serum creatinine more than 1.5-fold above the ULN
• History of substance abuse or alcohol abuse (defined as more than 10 standard drinks per week or regularly consuming more than 4 standard drinks on any one day; where 1 standard drink is 10 g of pure alcohol and is equivalent to 285 mL beer (4.9% Alc./Vol), 100 mL wine (12% Alc./Vol), 30 mL spirit (40% Alc./Vol) within 12 weeks prior to the screening visit
• Positive drugs of abuse or alcohol breath test results at the screening visit or at check-in (Day -1).
• Use of any prescription or over-the-counter medication (including herbal products, diet aids, and hormone supplements) within 10 days or 5 half-lives of the medication (whichever is longer) prior to the first study drug administration, except use of contraceptives and occasional use of paracetamol (doses of 500 mg up to every 6 hours or 2 g per day maximum for no more than 3 consecutive days)
• Consumption of grapefruit or Seville orange (or products containing grapefruit or Seville orange) within 10 days prior to the first administration of study drug
• Demonstrated clinically significant (required intervention, e.g., emergency room visit, epinephrine administration) allergic reactions (e.g., food, drug, or atopic reactions, asthmatic episodes) which, in the opinion of the Investigator, would interfere with the volunteer’s ability to participate in the trial
• Known hypersensitivity to any of the study drug ingredients
• Use of any vaccinations within 14 days prior to the first study drug administration
• For women of childbearing potential, a positive serum pregnancy test at the screening visit or a positive urine pregnancy test (with confirmatory serum pregnancy test) at check-in (Day -1)
• Females who are breastfeeding or planning to breast feed at any time during the study
• Donation of blood or plasma within 30 days prior to first study drug administration, or loss of whole blood of more than 500 mL within 30 days prior to first study drug administration, or receipt of a blood transfusion within 1 year of first study drug administration
• Participation in another clinical trial of an investigational drug within 60 days or 5 half-lives of the investigational agent (whichever is longer) prior to the first study drug administration
• Any other condition or prior therapy that in the opinion of the Investigator would make the volunteer unsuitable for this study, including inability to cooperate fully with the requirements of the study protocol or likelihood of noncompliance with any study requirements