Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PN-881 in Healthy Subjects.

PN-881 will be administered in oral solution and tablet formulations, with dosing under fasting or fed conditions depending on the study part.

The study consists of five parts:

Part 1 - Single Ascending Dose (SAD): Randomised, double-blind, placebo-controlled Part 2 - Multiple Ascending Dose (MAD): Randomised, double-blind, placebo-controlled Part 3 - Tablet Formulation Comparison: Open-label, crossover design; participants will receive different oral tablet formulations Part 4 - Effect of Food: Open-label, crossover design to assess the effect of food on the pharmacokinetics of PN-881. Participants will receive PN-881 tablet formulations in fasted and fed conditions.

Part 5 - Dosing Frequency Comparison: Open-label, randomized study comparing once-daily and twice-daily dosing.

Inclusion criteria

• Healthy male and female participants of non-childbearing potential, aged 18-65 years inclusive
• Body mass index (BMI) between 18 and 32 kg/m² (inclusive) at screening
• Willing and able to comply with all study requirements and provide written informed consent
• Male participants with female partners of childbearing potential must agree to use highly effective contraception during the study and for 90 days after the last dose

Exclusion criteria

• Clinically significant history or presence of cardiovascular, gastrointestinal, hepatic, renal, neurological, psychiatric, or allergic diseases
• History of neoplastic disease (except adequately treated non-melanoma skin cancer)
• Positive test for hepatitis B, hepatitis C, or HIV at screening
• History of substance abuse or recreational IV drug use within the past 2 years
• Clinically significant infection or fever (>38°C) within 2 weeks prior to screening
• Use of any prescription/non-prescription drugs or herbal supplements within 7 days or 5 half-lives before dosing (unless approved by investigator)
• Supine blood pressure or ECG abnormalities outside protocol-defined ranges
• Use of tobacco/nicotine products exceeding 5 cigarettes/day or 2 chews/day
• Consumption of >21 alcohol units/week (males) or >14 units/week (females)