TOFO Insulin Combination Trial

Study Overview
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Brief Summary
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Primary Objectives: To assess the effects of tofogliflozin on glycemic control in comparison to placebo as an add-on treatment to insulin treatment in terms of glycated hemoglobin (HbA1c) reduction over a period of 16 weeks in patients with type 2 diabetes mellitus. To assess the safety of tofogliflozin in combination with insulin treatment throughout 52 weeks. Secondary Objectives: To assess the effects of tofogliflozin in comparison to placebo on: Body weight Fasting plasma glucose (FPG) Postprandial plasma glucose (PPG) To assess the long term safety and tolerability of tofogliflozin.

Detailed Description
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The total study duration from screening for a patient can be approximately up to 1 year, including a screening period of 2 weeks, double-blinded placebo controlled treatment period of 16 weeks, an open-labeled extension period of 36 weeks, and a follow-up period of 3 days.

Official Title
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A Randomized, Double Blind Placebo Controlled 2-Arm Parallel Group, Multicenter Study With A 16-Week Treatment Assessing The Efficacy And Safety, And 52-Week Long Term Safety Including 36-Week Open Label Extension Of Tofogliflozin With Insulin Treatment In Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: TOFOGLIFLOZIN CSG452
* Drug: insulin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients aged 20-75 years old with type 2 diabetes mellitus (T2DM). Hemoglobin A1c ≥7.5% - ≤10.5% and FPG ≤220 mg/dL. Basal bolus (BB), Bolus, Premix, Basal supported oral therapy (BOT) regimens used for more than 12 weeks before screening. Stable dose (-/+20%) of insulin and no change in the dose of oral hypoglycemic agents for more than 12 weeks before screening. Only Dipeptidyl peptidase-4 inhibitor is allowed for basal supported oral therapy (BOT) regimen. Body mass index (BMI) ≥18.5 kg/m^2 and <35.0 kg/m^2. No change of antihypertensive, anti-hypercholesterolemia and uric acid lowering drug 4 weeks before screening. Exclusion criteria: Type 1 diabetes mellitus. Pregnancy or lactation. Severely uncontrolled glycemic situation. History of metabolic acidosis, including diabetic ketoacidosis, within 1 year prior to screening. History of myocardial infarction, stroke, or heart failure requiring hospitalization or drug or alcohol abuse within the previous 6 months. A measured serum creatinine level greater than 2.0 mg/dL for men and 1.5 mg/dL for women. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥2.5 times the upper limit of the reference range at the central laboratory test facility. Has previously received treatment with the investigational product. Has received treatment with another investigational product or non-approved drug within 3 months before tests for provisional enrolment. Corticosteroid therapy for 14 or more days in total within 8 weeks before tests for provisional enrolment (excluding those used for localized effects, such as drugs for topical [skin] application, eye drops and sprays). Patients who are frequently experiencing orthostatic hypotension. Required a change in the dosing regimen for the following drugs within 4 weeks before tests for provisional enrolment: Lipid-lowering drug Antihypertensive drug Thyroid hormone preparation Uric acid lowering drug The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 20 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: tofogliflozin<br>Tofogliflozin administered once daily for 52 weeks. Insulin administered as base treatment. | Drug: TOFOGLIFLOZIN CSG452<br>* Pharmaceutical form:tablet Route of administration: oral<br>* Other names: Deberza;Drug: insulin<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>|
| Placebo Comparator: placebo<br>Placebo administered once daily for 16 weeks. After 16-weeks, Tofogliflozin administered once daily for 36 weeks. Insulin administered as base treatment. | Drug: TOFOGLIFLOZIN CSG452<br>* Pharmaceutical form:tablet Route of administration: oral<br>* Other names: Deberza;Drug: insulin<br>* Pharmaceutical form:solution Route of administration: subcutaneous<br>Drug: placebo<br>* Pharmaceutical form:tablet Route of administration: oral<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c from baseline |  | 16 weeks after first intake of investigational product | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Body Weight (BW) from baseline |  | 16 weeks after first intake of investigational product | 
| Change of FPG from baseline |  | 16 weeks after first intake of investigational product | 
| Change of PPG from baseline |  | 16 weeks after first intake of investigational product | 
| Number of subjects with adverse events |  | Up to 52 weeks from the first intake of investigational medicinal product |