Multiple-dose Tolerability and Pharmacokinetic of IBI362 in Chinese Patients With T2DM

Study Overview
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Brief Summary
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This trial is aimed to investigate the safety, tolerability, PK and PD of multiple subcutaneous injections of IBI362 in Chinese patients with type 2 diabetes who have poor glycemic control after lifestyle or metformin intervention

Detailed Description
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This is a multicenter, randomized, double-blind, placebo-controlled trial, the first trial to assess the safety, tolerability, and PK/PD of IBI362 administered as multiple injections in Chinese patients with type 2 diabetes. The investigators and subjects will be blinded to the study drug IBI362 and placebo. Dulaglutide will be used as an open-label active control group. In this trial, 42 eligible patients will be recruited and randomly allocated to three cohorts. Each corhot will be randomized as an 8:4:2 ratio to IBI362 (n = 8), placebo (n = 4), and Dulaglutide 1.5 mg (n = 2).

Official Title
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A Multiple Dose Human Tolerability and Pharmacokinetic Study of IBI362 in Chinese Patients With Type 2 Diabetes Mellitus and Poor Glycemic Control

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: IBI362
* Drug: Placebo
* Drug: Dulaglutide


Participation Criteria
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Eligibility Criteria
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* Eligibility Criteria： Inclusion Criiteria: Male or female 18 to 75 years of age at the time of consent. T2D patients with poorly controlled blood glucose treated with lifestyle intervention or stable dose of metformin (≥ 1000mg/day or maximum tolerated dose) within 2 months prior to screening. HbA1c 7.5% ≤ 11.0% by local laboratory at screening. Body mass index 20 ≤ BMI ≤ 35 kg/m2. Exclusion Criteria: Type 1 diabetes, special types of diabetes, or gestational diabetes. Ketoacidosis or lactic acidosis within 6 months prior to screening. History of severe hypoglycaemic episodes within 6 months prior to screening. Acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting, coronary intervention (except diagnostic angiography), transient ischemic attack (TIA), cerebrovascular accident, acute and chronic heart failure within 6 months before screening. Clinically symptomatic liver disease, acute or chronic hepatitis, or transaminases (ALT and AST) and alkaline phosphatase (ALP) > 2 times the upper limit of normal and total bilirubin above the upper limit of normal at screening. The patient was previously diagnosed with autonomic neuropathy, manifested as urinary retention, resting tachycardia, orthostatic hypotension and diabetic diarrhea.

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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IBI362 low dose cohort<br>Participants receive low dose level of IBI362, matched placebo or Dulaglutide administrated by multiple subcutaneous injection. | Drug: IBI362<br>* Administrated by subcutaneous injection<br>Drug: Placebo<br>* Administrated by subcutaneous injection<br>Drug: Dulaglutide<br>* Administrated by subcutaneous injection<br>|
| Experimental: IBI362 medium dose cohort<br>Participants receive medium dose level of IBI362, matched placebo or Dulaglutide administrated by multiple subcutaneous injection | Drug: IBI362<br>* Administrated by subcutaneous injection<br>Drug: Placebo<br>* Administrated by subcutaneous injection<br>Drug: Dulaglutide<br>* Administrated by subcutaneous injection<br>|
| Experimental: IBI362 high dose cohort<br>Participants receive high dose level of IBI362, matched placebo or Dulaglutide administrated by multiple subcutaneous injection | Drug: IBI362<br>* Administrated by subcutaneous injection<br>Drug: Placebo<br>* Administrated by subcutaneous injection<br>Drug: Dulaglutide<br>* Administrated by subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the number and incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of IBI362 compared with placebo | Number of subjects with treatment emergent adverse events and serious adverse events through the end of the follow-up period | From the first dose of study drug to week 19 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The PK/PD parameters of IBI362 in patients with T2DM |  | From Baseline to week 12 | 
| Evaluate the Peak Plasma Concentration (Cmax) of IBI362 in patients with T2DM |  | From Baseline to week 12 | 
| Evaluate the Area under the plasma concentration versus time curve (AUC) of IBI362 in patients with T2DM |  | From Baseline to week 12 | 
| Evaluate the Fasting Blood Glucose (FBG ) of IBI362 in patients with T2DM |  | From Baseline to week 12 | 
| Evaluate the Glucagon of IBI362 in patients with T2DM |  | From Baseline to week 12 | 
| Evaluate the Insulin of IBI362 in patients with T2DM |  | From Baseline to week 12 | 
| Evaluate the C-peptide of IBI362 in patients with T2DM |  | From Baseline to week 12 | 
| Number of Participants With Anti-IBI362 Antibodies | Serum samples will be analyzed by an electrochemiluminescence (ECL)-based immunoassay for anti-IBI362 binding antibodies. Positive samples will be subsequently tested in a receptor-ligand binding bioassay for anti-IBI362 neutralizing antibodies. | From the first dose of study drug to week 19 |