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

Prior treatment

• History of diabetic ketoacidosis or severe hypoglycemia (ADA Level 3) in the 6 months prior to Screening
• 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
• Receipt of investigational products within 30 days

Other illness

• 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
• Any physical or psychological condition that prohibits study completion
• Known cardiac disease
• HIV, hepatitis B and/or hepatitis C positive
• Any physical or psychological condition that prohibits study completion
• Known cardiac disease
• active autoimmune disease requiring immunosuppression
• HIV, hepatitis B and/or hepatitis C positive

Other

• Phase 1 Parts 1, 2 and 3:
• Blood donation within 30 days
  • Phase 2 Part 4:
• Current use of insulin (except ≤20 units/day stable basal insulin for ≥12 weeks
• Daily insulin requirement \>1.0 units/kg/day
• diabetic retinopathy
• symptomatic neuropathy
• nephrotic-range proteinuria

• 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