Janagliflozin Treat T2DM Monotherapy

Study Overview
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Brief Summary
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The purpose of this study is to assess the effect of Janagliflozin relative to placebo on glycated hemoglobin (HbA1c) after 24 weeks of treatment, and to assess the efficacy after 52 weeks of treatment, overall safety and Population pharmacokinetics.

Detailed Description
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A multicentre, randomized, double-blind, parallel group, placebo-controlled study(24 weeks core period followed by 28 Weeks Extension period), to evaluate the efficacy and safety of Janagliflozin (25 mg and 50 mg) compared to placebo in patients diagnosed with T2DM who are not achieving an adequate response from diet and exercise to control their diabetes. Approximately 390 patients with inadequate glycemic control with diet and exercise will receive once-daily double-blind treatment with Janagliflozin 25 mg or 50 mg once daily for 52 weeks, or 24 weeks of double-blind treatment with placebo followed by 28 weeks of single-blind treatment with Janagliflozin 25 mg or 50 mg. During the treatment, if a patient's glycemic level remains high despite treatment with study drug and reinforcement with diet and exercise, the patient will receive treatment with metformin (rescue therapy) consistent with local prescribing information. Study drug will be taken orally once daily.

Official Title
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A Multicentre, Randomized, Double-blind, Parallel Group, Placebo-controlled Study, to Evaluate the Efficacy and Safety of Janagliflozin (25 mg and 50 mg) as Monotherapy in Chinese Patients Diagnosed With T2DM

Conditions
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Diabetes Type 2

Intervention / Treatment
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* Drug: Janagliflozin 25mg
* Drug: Janagliflozin 50mg
* Drug: Placebo/Janagliflozin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients must have a diagnosis of T2DM (meet the diagnostic criteria for diabetes issued by the World Health Organization in 1999) Patients must have a hemoglobin A1c (HbA1c) level ≥7.5% and ≤11% at screening, and ≥7.0% and ≤10.5% at baseline. Drug -naïve (never received anti-diabetic medication or did not receive anti-diabetic medication within 8 weeks before screening). Body Mass Index: 18.0 35.0 kg/m2 (both inclusive) Exclusion Criteria: History of type 1 diabetes mellitus (T1DM), diabetes caused by pancreatic injury, or secondary diabetes (e.g., diabetes caused by Cushing's syndrome or acromegaly) More than 10% change in body weight within the 3 months before screening Any laboratory test indicators meet the following standards: fasting plasma glucose ≥ 15 mmol/L aspartate aminotransferase, alanine aminotransferase levels > 3 times the upper limit of normal (ULN); total bilirubin > 1.5 times ULN hemoglobin < 100 g/L eGFR < 60 mL/min/1.73m2 fasting triglycerides > 5.64 mmol/L (500 mg/dL)

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: Janagliflozin 25mg<br>Each patient will receive 25 mg of Janagliflozin once daily for 52 weeks (24 weeks core period followed by 28 Weeks Extension period) | Drug: Janagliflozin 25mg<br>* Tablets, Oral, 25 mg, Tablets, Oral, 50 mg<br>* Other names: Placebo 50mg;|
| Experimental: Janagliflozin 50mg<br>Each patient will receive 50 mg of Janagliflozin once daily for 52 weeks (24 weeks core period followed by 28 Weeks Extension period) | Drug: Janagliflozin 50mg<br>* Tablets, Oral, 25 mg, Once daily, 52 weeks<br>* Other names: Placebo 25mg;|
| Experimental: Placebo/Janagliflozin<br>In the core period, each patient will receive placebo once daily for 24 weeks and will then switch from placebo to 25 mg or 50 mg of Janagliflozin once daily until Week 52. | Drug: Placebo/Janagliflozin<br>* Tablets, Oral, 25 mg, Once daily, 52 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to Week 24 | To examine whether the mean change in HbA1c from baseline to week 24 with Janagliflozin is superiority (superiority margin of 0.5%) to placebo | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c From Baseline to Week 52 | To compare the mean change in HbA1c from baseline to week 52 between groups | Baseline and Week 52 | 
| Percentage of Patients With HbA1c <7% at Week 24 (Core period) and week 52 | To compare the percentage of patients with HbA1c <7% at week 24 (core period) and week 52 (extension period) between groups | Baseline, Week 24 and week 52 | 
| Percentage of Patients With HbA1c <6.5% at Week 24 (Core period) and Week 52 (Extension period) | To compare the percentage of patients with HbA1c <6.5% at week 24 (core period) and Week 52 (extension period) between groups | Baseline, Week 24 and Week 52 | 
| Change in Fasting Plasma Glucose (FPG) From Baseline to Week 24 (Core period) and Week 52 (Extension period) | To compare the mean change in fasting plasma glucose (FPG) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups | Baseline, Week 24 and Week 52 | 
| Change in 2-hour Post-prandial Glucose From Baseline to Week 24 (Core period) and Week 52 (Extension period) | To compare the mean change in 2-hour post-prandial glucose from Baseline to Week 24 (core period) and Week 52 (extension period) between groups | Baseline, Week 24 and Week 52 | 
| Change in Blood Lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) From Baseline to Week 24 (Core period) and Week 52 (Extension period) | To compare the mean change in blood lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups | Baseline, Week 24 and Week 52 | 
| Change in Blood Pressure (systolic blood pressure and diastolic blood pressure) From Baseline to Week 24 (Core period) and Week 52 (Extension period) | To compare the mean change in blood pressure (systolic blood pressure and diastolic blood pressure) from Baseline to Week 24 (core period) and Week 52 (extension period) between groups | Baseline, Week 24 and Week 52 | 
| Change in Body Weight From Baseline to Week 24 (Core period) and Week 52 (Extension period) | To compare the mean change in body weight from Baseline to Week 24 (core period) and Week 52 (extension period) between groups | Baseline, Week 24 and Week 52 | 
| Change in Fasting C-peptide From Baseline to Week 24 (Core period) and Week 52 (Extension period) | To compare the mean change in fasting C-peptide from Baseline to Week 24 (core period) and Week 52 (extension period) between groups. | Baseline, Week 24 and Week 52 | 
| Change in Insulin Sensitivity From Baseline to Week 24 (Core period) and Week 52 (Extension period) | To compare the mean change in insulin sensitivity from Baseline to Week 24 (core period) and Week 52 (extension period) between groups | Baseline, Week 24 and Week 52 | 
| Change in β-cell Function From Baseline to Week 24 (Core period) and Week 52 (Extension period) | To compare the mean change in β-cell function from Baseline to Week 24 (core period) and Week 52 (extension period) between groups. | Baseline, Week 24 and Week 52 | 
| Percentage of Patients Who Have Received Rescue Therapy at Week 24 (Core period) and Week 52 (Extension period) | To compare the percentage of patients who have received rescue therapy by Week 24 (core period) and Week 52 (extension period) between groups | Week 24 and Week 52 |