Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PAL-119 in Healthy Volunteers and Adult Participants With Type 1 or Type 2 Diabetes

This is a Phase 1/2 randomized study of oral doses of PAL-119 in healthy volunteers and participants with diabetes.

Inclusion Criteria: Phase 1 Parts 1, 2 and 3 * Healthy volunteers age 18 to 55 years of age * Medically healthy with no clinically significant findings * BMI 18-35 kg/m² * eGFR ≥90 * Able and willing to provide written informed consent * Able to swallow an oral solid-dosage form of medication. * Willing and able to follow a low-tyramine diet and abstain from prohibited medications from 48 hours prior to first dose and for the duration of the study and for 14 days after the last dose * Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies * ability to consume high-fat meal (Part 3 only) Phase 2 Part 4: * 18 to ≤70 years of age * Confirmed Type 2 diabetes diagnosis ≥6 months and ≤15 years prior to screening * BMI 25 to 40 kg/m² at Screening * Able and willing to provide written informed consent * Stable diabetes therapy for ≥12 weeks prior to screening visit * Willing and able to follow a low-tyramine diet and abstain from prohibited medications for the duration of the study and for 14 days after the last dose * Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies Phase 2 Part 5 * 18 to ≤70 years of age * Confirmed Type 1 diabetes diagnosis ≥6 months and ≤10 years prior to screening visit * Stable insulin regimen for ≥12 weeks prior to screening visit * Willingness to use continuous glucose monitoring (CGM) for continuous periods during the study * Able and willing to provide written informed consent * Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies * Willing and able to follow a low-tyramine diet and abstain from prohibited medications for the duration of the study and for 14 days after the last dose Exclusion Criteria: Phase 1 Parts 1, 2 and 3: * Any physical or psychological condition that prohibits study completion * Known cardiac disease * HIV, hepatitis B and/or hepatitis C positive * Active or history of malignancy * Blood donation within 30 days Phase 2 Part 4: * History of diabetic ketoacidosis or severe hypoglycemia (ADA Level 3) in the 6 months prior to Screening * Current use of insulin (except ≤20 units/day stable basal insulin for ≥12 weeks * Any physical or psychological condition that prohibits study completion * Known cardiac disease * HIV, hepatitis B and/or hepatitis C positive * Receipt of investigational products within 30 days Phase 2 Part 5: * History of diabetic ketoacidosis or severe hypoglycemia (ADA Level 3) in the 6 months prior to Screening * Daily insulin requirement \>1.0 units/kg/day * Any physical or psychological condition that prohibits study completion * Known cardiac disease * active autoimmune disease requiring immunosuppression * diabetic retinopathy * HIV, hepatitis B and/or hepatitis C positive * symptomatic neuropathy * nephrotic-range proteinuria * Receipt of investigational products within 30 days