A Phase 1, Double-blind, Randomized, Placebo-controlled, Single- and Multiple-dose Escalating Study

A Phase 1, double-blind, randomized, placebo-controlled, single and multiple-dose escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PB-718 following subcutaneous administration in healthy subjects.

Inclusion criteria

• Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
• Males or females, of any race, between 18 and 55 years of age, inclusive.
• Male subjects will weigh at least 50 kg, and female subjects will weigh at least 45 kg. Body mass index between 20.0 and 30.0 kg/m2 (Part A) or 25.0 to 50.0 kg/m2 (Part B), inclusive.
• In good health, determined by no clinically significant findings from medical history, physical examination, 12-lead ECG, vital signs measurements, and clinical laboratory evaluations (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at Screening and Check-in/predose as assessed by the Investigator (or designee).

Exclusion criteria

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, renal, hematological, pulmonary, cardiovascular or other heart disease, gastrointestinal, urinary/prostatic, neurological, respiratory, endocrine, or psychiatric disorder, or glaucoma, as determined by the Investigator (or designee).
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
• Liver disease or liver injury, as indicated by abnormal liver function tests (e.g. serum bilirubin, direct bilirubin, ALT, AST, γ-GT, or ALK exceeding the ULN) at Screening or Baseline which may be repeated for confirmation per the Investigators discretion at Screening and Check-in.
• History of multiple endocrine neoplasia type 2 or an abnormal thyroid function test (thyroid stimulating hormone, triiodothyronine, thyroxine) at Screening or Baseline.
• Fasting plasma glucose greater than ≥126 mg/dL at Baseline.
• Hemoglobin A1c value >6.5%
• History of chronic or acute pancreatitis, or amylase or lipase exceeding 2 × ULN at Screening or Baseline. -