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

This will be a randomized, double-blind, placebo-controlled, single- and multiple SC dose escalating study conducted in 2 parts.

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:

1. Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
2. Males or females, of any race, between 18 and 55 years of age, inclusive.
3. 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.
4. 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:

1. 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).
2. 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.
3. 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.
4. History of multiple endocrine neoplasia type 2 or an abnormal thyroid function test (thyroid stimulating hormone, triiodothyronine, thyroxine) at Screening or Baseline.
5. Fasting plasma glucose greater than ≥126 mg/dL at Baseline.
6. Hemoglobin A1c value >6.5%
7. History of chronic or acute pancreatitis, or amylase or lipase exceeding 2 × ULN at Screening or Baseline. -