Safety and Efficacy of PB-119 in Subjects With Type 2 Diabetes and Not Well-controlled by Metformin Monotherapy

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of 24 once-weekly subcutaneous doses of PB-119 to subjects with type 2 diabetes mellitus (T2DM) not well-controlled by metformin monotherapy.

Detailed Description
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This is a phase 3 multicenter, randomized, double-blind, placebo-controlled, parallel dose cohort study to evaluate the efficacy and safety 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,a 24-week double-blind treatment period and a 28-week open-label treatment period. The eligible patients will be randomized to PB-119 or placebo cohort at a 1:1 ratio for the first 24-week. Patients in PB-119 group will subsequently be given active drug and patients in placebo group will take placebo, all patients in two groups will remain metformin background therapy. In the 28-week open-label period, all patients will be administered active drugs. After that, there will be a 4-week follow-up period; All randomized patients will be taken blood samples for the pharmacokinetic (PK) analysis.

Official Title
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A Multicenter, Randomized, Double-blinded, Placebo-controlled Trial Comparing the Efficacy and Safety of PB-119 in Combination With Metformin in Subjects With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin Alone

Conditions
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Type 2 Diabetes Mellitus (T2DM)

Intervention / Treatment
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* Drug: GLP-1 receptor agonist
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, aged 18 75 years old; T2DM and treated with Metformin ≥ 1500mg/day or maximum tolerated dose(≥1000mg,<1500mg) constantly for at least 8 consecutive weeks; 7.5% ≤ HbA1c ≤ 10.0% at screening; 18.5 kg/m2 < BMI < 40.0 kg/m2 at screening; Exclusion Criteria: Any anti-diabetic therapy other than Metformin within 8 weeks before screening； T1DM; Received insulin therapy more than 14 days within 1 year before screening; Female who is pregnant, breast-feeding; Any disorder which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol; History of acute diabetic complications, such as diabetic ketoacidosis or hyperglycemic hyperosmolar status within 6 months before screening； History or presence of pancreatitis (acute or chronic); Presence or history of malignant neoplasms within the past 5 years prior to the day of screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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 once-weekly-subcutaneous injection<br>PB119 (polyethylene glycol exenatide) is a long-acting GLP-1RA for injection, which will be administered 150μg once-weekly subcutaneously to patients in active drug group for 24 weeks. | Drug: GLP-1 receptor agonist<br>* PB-119 is an investigational pegylated human glucagon-like peptide-1 (GLP-1) receptor agonist. The dosing regimen is 150μg once every week as subcutaneous administration. Patients in PB-119 group will be administered the active drugs for 52 weeks (24+28).<br>|
| Placebo Comparator: Placebo once-weekly-subcutaneous injection<br>PB-119 150μg matched placebo which will be used in placebo group for 24 weeks. | Drug: Placebo<br>* PB-119 matched placebo will be used once every week as subcutaneous administration to placebo group for 24 weeks.<br>* Other names: PB-119 Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Change in HbA1c from baseline(week 1) to week 25 | week 1, week 25 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c Below 7.0% | Percentage of participants with HbA1c below 7.0% was evaluated at week 25. | week 1, week 25 | 
| Change in Body Weight (kg) | Change from baseline (week 1) in body weight was evaluated at week 25 | week 1, week 25 | 
| Change in Fasting Plasma Glucose (FPG) | Change from baseline (week 1) in FPG was evaluated at week 25 | week 1, week 25 | 
| Change in Body Mass Index | Change from baseline (week 1) in body mass index (BMI) was evaluated at week 25. | week 1, week 25 |