A Phase I, Randomized, Double-Blind, Placebo-Controlled, Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of Orally Administered PRN2246 in Healthy Volunteers

Exclusion Criteria26

• Pregnant or lactating women, and male partners of women who are pregnant or lactating
• Women of child-bearing potential
• Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV)
• Any active acute or chronic disease or infection judged to be clinically significant by the Investigator
• Use of more than 1-2 tobacco/nicotine-containing or cannabis products per month within 6 months prior to the first study drug administration
• Participant is febrile, temperature > 37.5 °C. at screening, clinic check-in/ Day -1, or pre dose
• History or presence of alcoholism or drug abuse within the 2 years prior to the first study drug administration
• History of any significant (as determined by the Investigator) drug-related allergic reactions such as, anaphylaxis, Stevens-Johnson syndrome, urticaria or multiple drug allergies
• Use of any over-the-counter (OTC) medication, including herbal products, within the 7 days prior to Day 1, other than limited paracetamol use (less than or equal to 2g/day). Use of any prescription medication within the 14 days prior to the first study drug administration or 5 half-lives, whichever is longer
• Blood donation or significant blood loss within 60 days prior to screening
• Plasma donation within 14 days prior to the first study drug administration
• Participation in another clinical trial of a drug or device whereby the last investigational drug/device administration is within 60 days prior to the first study drug administration or 5 half-lives, whichever is longer
• Surgery within the past three months prior to the first study drug administration determined by the Investigator to be clinically relevant
• Personal or family history of prolonged QT syndrome or family history of sudden cardiac death
• QTcF > 450 msec (males) or > 470 msec (females) or < 300 msec at screening or baseline visit, or deemed clinically significant by the Investigator
• Screening ECG with QRS and/or T-wave judged to be unfavorable for a consistently accurate QT measurement as judged by the Investigator
• History of active treatment for tuberculosis within the past 5 years
• Receipt of a live vaccine within 60 days prior to Day 1 thru to the study follow-up visit
• Evidence of atrial fibrillation, atrial flutter, complete bundle branch block, Wolff-Parkinson-White Syndrome, or cardiac pacemaker at screening or baseline visit
• Resting systolic blood pressure (SBP) greater than 140 or less than 90 mm Hg, or diastolic blood pressure greater than 90 or less than 50 mm Hg
• Resting HR < 45 pm or > 90 bpm at screening or baseline visit
• Hypersensitivity or history of idiosyncratic reaction to any components or excipients of the investigational or placebo formulation
• Regular alcohol consumption > 14 units per week (1 unit equals ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine)
• Failure to satisfy the Investigator of fitness to participate for any other reason
• History or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic, neurological, or psychiatric disease
• Any significant acute illness within 30 days prior to Day 1