A Phase 1 Randomized, Double-Blind, Placebo-Controlled Study With A Food Effect Assessment To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Single Ascending Doses And Multiple Ascending Doses Of PX578 In Healthy Adult Participants (Part A & B)

Exclusion Criteria29

• Clinically-significant medical history or ongoing chronic illness that, in the opinion of the study Investigator, would jeopardize the safety of the participant or compromise the integrity of the data derived from their participation in this study.
• History of any depression, anxiety or sleep disorders requiring clinical intervention over the past 12 months.
• Clinically-significant infection of any kind requiring systemic antimicrobial therapy or hospitalization within 4 weeks prior to the first dose of study drug.
• Clinically-significant abnormal findings at Screening on physical examination, ECG, or laboratory testing in the opinion of the Investigator.
• QTcF > 470 ms (females) or > 450 ms (males) at Screening or Day -1 based on the mean of triplicate ECGs.
• Liver test results during Screening or at check-in day (Day -1) that are above the upper limit of normal (ULN) for gamma-glutamyl transferase, bilirubin (total), aspartate aminotransferase (AST) or alanine aminotransferase (ALT), unless a diagnosis of Gilbert syndrome. For history of Gilbert syndrome, the limit is extended to 2-fold above the ULN.
• Positive test results for hepatitis B surface antigen (HBsAg), hepatitis C (HCV) antibody or human immunodeficiency virus (HIV) antibody at Screening. Participants who are positive for HCV antibody but do not have active HCV (ie, test negative for HCV RNA on a polymerase chain reaction [PCR] test) are eligible for the study.
• Estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2 at Screening using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 formula.
• History of active malignancy within 3 years prior to Screening, except basal cell carcinoma of the skin, curatively resected squamous cell carcinoma of the skin, cervical carcinoma in situ curatively treated or low-grade prostate adenocarcinoma for which appropriate management is observation alone.
• History of surgery or hospitalization within 3 months prior to Screening, or surgery planned during the study.
• History of hypersensitivity, allergic or anaphylactic reactions to the study drug ingredients or other therapeutic proteins.
• History of drug or alcohol abuse (as defined by the Investigator) within 5 years prior to Screening, a positive urine drug or alcohol test at Screening or Day -1, or an unwillingness to abstain from drugs of abuse throughout the study, or from alcohol for 48 hours prior to Day -1 and for the duration of the study.
• Participant smokes more than 5 cigarettes or equivalent nicotine-containing products per day, and/or is unwilling to abstain from smoking or the use of nicotine-containing products for 72 hours prior to check-in on Day -1 and throughout the study.
• Note: 1 average cigar equals approximately 5 average cigarettes; 1 average pipe session equals approximately 5 average cigarettes; 1 average nicotine liquid vape session equals 1 average e-cigarette equals 1 average cigarette.
• Has a positive urine screen for cotinine at Day -1.
• Unwilling to abstain from caffeine containing products for 24 hours prior to Day -1 and for the duration of the study.
• Unwilling to abstain from eating cruciferous vegetables, charcoal-grilled meats, and poppy seeds for 48 hours prior to Day -1 and for the duration of the study.
• Unwilling to refrain from consumption of Seville oranges, grapefruit or grapefruit juice, [pomelos, exotic citrus fruits, grapefruit hybrids, or their juices] within 14 days of Day -1 and for the duration of the study.
• Substance abuse, mental illness, or any reason that makes it unlikely in the judgment of the Investigator for the participant to be able to comply fully with study procedures.
• Females who are pregnant (positive pregnancy test at Screening or during the study), lactating, or, if having reproductive potential, are considered potentially unreliable with respect to contraceptive practice.
• Use of prescription medication (with the exception of oral contraceptives) within 7 days or 5 half-lives prior to initiation of study drug dosing (whichever is longer) and for the duration of the study.
• Participant is using medications which are exogenous modulators of CYP pathways as identified in the Flockhart table (Flockhart Table)
• Participant has taken over-the-counter medications including herbal/dietary supplements, protein powders/creatinine, or homeopathic preparations within 7 days prior to initiation of study drug dosing (within 28 days of Day -1 or 10 half lives, whichever is longer, for St John’s Wort). Prophylactic doses of vitamin/mineral supplements and occasional paracetamol or ibuprofen are allowed.
• Participation in any clinical study of an investigational drug or investigational device within 30 days or 5 half-lives of the investigational drug (whichever is longer) prior to Day 1.
• Administration of any live, attenuated vaccines within 30 days and all other vaccinations within 14 days prior to initiation of study drug dosing.
• Participant has donated or lost greater than or equal to 400 mL blood in the 6 weeks prior to Day 1.
• Participant is unable to swallow oral medication.
• Participant has an inability to follow a standardized meal schedule and diet or inability to fast, as required by the study protocol.
• NOTE: Potential study participants with abnormal laboratory values may be rescreened once for specific laboratory tests within the Screening period (up to 4 weeks prior to dosing) before being designated a Screen failure. Repeat values within the normal range must be confirmed at Day -1 for inclusion.