Dose-finding of PB-119 Administered Subcutaneously Once Weekly Versus Placebo in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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A phase 2, multicenter study to evaluate the efficacy and safety of twelve once weekly subcutaneous doses of PB-119 to patients with type 2 diabetes mellitus (T2DM) not well-controlled by metformin mono therapy.

Detailed Description
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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 to patients with T2DM not well-controlled by metformin monotherapy. Patients will be assessed for eligibility over a 2 week screening period prior to a 4-week run-in period and a 12-week double-blind treatment period.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 to patients with type 2 diabetes mellitus (T2DM) not well-controlled by metformin monotherapy 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 1) active drug or placebo at a 3:1 active drug:placebo ratio and 2) exclusion from or inclusion in the pharmacokinetic (PK) blood sample collection subgroup at a 3:1 excluded:included ratio

Official Title
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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 to Patients With Type 2 Diabetes Mellitus (T2DM) Not Well-controlled by Metformin Monotherapy

Conditions
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Type 2 Diabetes Mellitus (T2DM)

Intervention / Treatment
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* Drug: PB-119 100 μg+ Glucophage®
* Drug: PB-119 150 μg+ Glucophage®
* Drug: PB-119 200 μg+ Glucophage®
* Drug: PB-119 placebo + Glucophage®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients in whom T2DM has been diagnosed according to 2018 American Diabetes Association T2DM diagnostic criteria, have made lifestyle modifications (ie, diet and exercise) for at least 3 months prior to Screening, and have been taking metformin for at least 3 months before Screening with a stable dosage for at least 8 weeks (stable dosage is defined as metformin dosage ≥1500 mg/day or maximum tolerated dose). Males and/or females between the ages of ≥18 and ≤70 years at Screening HbA1c ≥7.5% and ≤11% at Screening and at Week -1, Visit 3.1; FPG ≥126 and ≤240 mg/dL (≥7.0 and ≤13.3 mmol/L) at Screening and at Week -1, Visit 3.1; Body mass index (BMI) ≥18.5 and ≤40.0 kg/m2 at Screening, with inclusion of patients with BMIs at the lower end of the range enrolled into the study to enable comparisons across BMI range; Exclusion Criteria: Medical history or current diagnosis of: Type 1 diabetes mellitus, diabetes caused by pancreas injury or by other diseases (like acromegaly or Cushing syndrome); Diabetes acute complication, like ketoacidosis or hyperosmolar coma; Diagnosed proliferative retinopathy; 3 instances of severe hypoglycemia (events during which the patient required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions; episodes may be associated with sufficient neuroglycopenia to have induced seizure or coma) in the 6 months prior to Screening; Significant vascular disease; Current/ongoing diagnosis of any type of malignant tumor or evidence of recurrence in the 6 months prior to Screening (patients who have been stable for ≥6 months or those who have had basal or squamous cell skin cancers removed and have no evidence of recurrence will not be excluded). Patients with a medical history of any other type of cancer in the last 5 years prior to Screening will be excluded; Severe cardiovascular diseases occurring within 6 months prior to Screening (eg, congestive heart disease, myocardial infarction, acute coronary syndrome, apoplexy, transient ischemic attack);

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PB-119 100 μg<br>PB-119 100 μg subcutaneous (SC) once weekly (QW) + Metformin oral (p.o.) Glucophage® (stable dosage) | Drug: PB-119 150 μg+ Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>Drug: PB-119 200 μg+ Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>Drug: PB-119 placebo + Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>|
| Experimental: PB-119 150 μg<br>PB-119 150 μg SC QW + Metformin oral (p.o.) Glucophage® (stable dosage) | Drug: PB-119 100 μg+ Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>Drug: PB-119 200 μg+ Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>Drug: PB-119 placebo + Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>|
| Experimental: PB-119 200 μg<br>PB-119 200 μg SC QW + Metformin oral (p.o.) Glucophage® (stable dosage) | Drug: PB-119 100 μg+ Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>Drug: PB-119 150 μg+ Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>Drug: PB-119 placebo + Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>|
| Placebo Comparator: PB-119 Placebo<br>PB-119 Placebo SC QW + Metformin oral (p.o.) Glucophage® (stable dosage) | Drug: PB-119 100 μg+ Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>Drug: PB-119 150 μg+ Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>Drug: PB-119 200 μg+ Glucophage®<br>* Each patient will subsequently be randomized within the designated cohort to active drug or placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from baseline value of HbA1c will be compared between treatments |  | From Baseline to end of treatment (up to Week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from baseline value of Fasting Plasma Glucose at Weeks 2, 4, 8, and 12 |  | From Baseline to end of treatment (up to Week 12) |