Dose-finding of PB-119 Administered Subcutaneously Once-weekly Versus Placebo in Drug-naïve T2DM Subjects

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Dose Cohort Study to Evaluate the Efficacy and Safety of Twelve Once-weekly Subcutaneous Doses of PB-119 in Drug-naïve Subjects With Type 2 Diabetes Mellitus

This is a multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort, multiple dose study to evaluate the efficacy, safety, and tolerability of different doses of PB-119 in drug-naïve subjects with T2DM.

Subjects will be assessed for eligibility over a 2-week screening period prior to a 2-week run-in period and a 12-week double-blind treatment period,4-week follow up period. The eligible patients will be randomized to 1 of 3 dose cohorts (A, B, or C). Each patient will subsequently be randomized within the designated cohort to active drug or placebo at a 3:1 active drug:placebo ratio.

Inclusion Criteria:

1. Males and/or females between the ages of ≥18 and ≤70 years at Screening
2. Patients in whom T2DM has been diagnosed according to 1999 WHOT2DM diagnostic criteria
3. HbA1c ≥7.5% and ≤11% at Screening and at Week -1
4. Body mass index (BMI) ≥18.5 and ≤35.0 kg/m2 at Screening

Exclusion Criteria:

1. Female who is pregnant, intends to become pregnant or breast-feeding or is of child-bearing potential and not using adequate contraception methods throughout the trial
2. Treatment with any glucose lowing agent(s) within 3 months prior to screening.An exception is short-term treatment (no longer than 7 days in total) with insulin in connection with inter-current illness
3. Calcitonin ≥50 ng/L at screening
4. Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia, type 2
5. Fasting triglyceride ≥500 mg/dL at Screening, or patients with a history of lipid disorders taking unstable treatment dosage (eg, statins) within 3 months prior to screening
6. Any acute or chronic condition that, in the opinion of the Investigator, would limit the patient's ability to complete and/or participate in this trial
7. Blood amylase or lipase >3x ULN, history of acute or chronic pancreatitis, or history of symptomatic gallbladder disease at Screening
8. Serum creatinine ≥1.5 mg/dL (male patients) or ≥1.4 mg/dL (female patients), or estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 at Screening
9. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2x upper limit of normal (ULN) at Screening and pre-randomization
10. Severe cardiovascular diseases occurring within 6 months prior to screening