To Compare the Efficacy and Safety of INS068 and Insulin Glargine in Subjects With Type 2 Diabetes Mellitus Not Adequately Controlled With Oral Antidiabetic Drugs

Study Overview
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Brief Summary
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The study is being conducted to evaluate the efficacy and safety of INS068 once daily (QD) in subjects with type 2 diabetes not adequately controlled with oral antidiabetic drugs compared to insulin Glargine QD for 26+26 weeks.

Official Title
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A Randomized, Open-Label, Controlled, Parallel-group, Multicenter Trial Comparing the Efficacy and Safety of INS068 and Insulin Glargine in Subjects With Type 2 Diabetes Mellitus Not Adequately Controlled With Oral Antidiabetic Drugs

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: INS068 injection
* Drug: Insulin Glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosed with type 2 diabetes ≥ 6 months； Stable daily dose(s) for ≥8 weeks prior to screening of any of the following anti-diabetic drug(s) or combination regimen(s): 1) Any metformin formulations ≥1500 mg daily or maximum tolerated (≥1000mg daily). 2) Any of the following oral antidiabetic drugs with dose ≥half of the maximum approved dose according to local label or maximum tolerated): Sulfonylureas, Meglitinides (glinides), dipeptidyl peptidase-4 (DPP-4) inhibitors, Sodium-glucose co-transporter-2 (SGLT2) inhibitors, Thiazolidinediones and Alpha-glucosidase inhibitors. Glycated hemoglobin was 7.0% 11.0% (both inclusive) at screening Exclusion Criteria: Known or suspected allergy or intolerance to the investigational medicinal products or related products； Hospitalization for diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome during the previous 6 months； Potentially unstable diabetic retinopathy or maculopathy requiring treatment (e.g., laser, surgical treatment or injectable drugs) during the previous 6 months； Have used insulin therapy anytime in the past 2 years, except for short-term insulin treatment and prior treatment for gestational diabetes. Participation in any clinical trial of an approved or non-approved investigational product/treatment within the last 1 month or 5 half-lives, whichever is longer, prior to screening; Women who are pregnant, breastfeeding or planning to conceive, or women of childbearing potential are reluctant to use appropriate contraception during the trial and for at least 14 days after the last dose of the investigational medicinal drug; Any conditions that the Investigator judges might not besuitable to participate in the trial.

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Randomized, Open-Label, Controlled, Parallel-group, Multicenter Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INS068 injection<br> | Drug: INS068 injection<br>* INS068 injected subcutaneously once daily. Treat-to-target dose titration during the trial<br>|
| Active Comparator: Insulin Glargine<br> | Drug: Insulin Glargine<br>* Insulin Glargine injected subcutaneously once daily. Treat-to-target dose titration during the trial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c | Change from baseline in Glycosylated Haemoglobin after 26 weeks of treatment | Week 0 to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in FPG(fasting plasma glucose) | Change from baseline in FPG after 26 weeks and 52 weeks of treatment | Week 0 to Week 26, Week 0 to Week 52 | 
| Proportion of Subjects with HbA1c<7% and HbA1c≤6.5% | Proportion of subjects with HbA1c<7% and HbA1c≤6.5% after 26 weeks and 52 weeks of treatment | Week 0 to Week 26 、Week 0 to Week 52 | 
| Proportion of Subjects achieving HbA1c targets (HbA1c<7%; HbA1c≤6.5%) and without grade 2 or 3 hypoglycaemia in the last 12 weeks of the treatment period |  | Week 0 to Week 26, Week 0 to Week 52 | 
| Change in HbA1c |  | Week 0 to Week 52 | 
| per-breakfast SMPG |  | Week 0 to Week 26 、Week 0 to Week 52 | 
| 8-point SMPG profiles |  | Week 0 to Week 26 、Week 0 to Week 52 | 
| Average daily Insulin dose |  | Week 0 to Week 26 、Week 0 to Week 52 | 
| Proportion of Subjects requiring rescue therapy during treatment |  | Week 0 to Week 26 、Week 0 to Week 52 | 
| Frequency and severity of adverse events |  | Week 0 to Week 52 + 14 days follow-up | 
| Incidence and rate of Hypoglycemic events |  | Week 0 to Week 52 + 14 days follow-up | 
| Change in weight |  | Week 0 to Week 26、Week 0 to Week 52 | 
| Anti-drug Antibodies |  | Week 0 to Week 52 + 14 days follow-up | 
| Serum INS068 concentration |  | Week 0 to Week 52 | 
| Change in scores of diabetes treatment satisfaction questionnaire status version (DTSQs) |  | Week 0 to Week 26 、Week 0 to Week 52 |