A Study of DS-8500a in Japanese Subjects With Type 2 Diabetes Mellitus Receiving Sitagliptin

Study Overview
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Brief Summary
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The objectives of the study is to evaluate the efficacy and safety of DS-8500a compared with placebo in patients with type 2 diabetes mellitus (T2DM) receiving sitagliptin.

Detailed Description
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In patients with type 2 diabetes mellitus being treated with sitagliptin, efficacy and safety of DS-8500a are to be evaluated after 28-day multiple oral administration of DS-8500a at 25 or 75 mg, in a double-blind, placebo-controlled, parallel-group comparison study.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled, add-on Study of DS-8500a in Japanese Patients With Type 2 Diabetes Mellitus Receiving Sitagliptin

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: DS-8500a 25 mg
* Drug: DS-8500a 75 mg
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Japanese patients with type 2 diabetes Patients aged ≥ 20 years at the time of informed consent Patients who have been treated with sitagliptin 50 mg monotherapy for the treatment of type 2 diabetes mellitus Patients who have HbA1c ≥ 7.0% and < 9.0% Exclusion Criteria: Patients with type 1 diabetes mellitus or with a history of diabetic coma, precoma, or ketoacidosis Patients receiving or requiring treatment with insulin Patients with a body mass index (BMI) of < 18.5 kg/m2 or ≥ 35.0 kg/m2 Patients with clinically evident renal impairment (estimated glomerular filtration rate [eGFR] of < 45 mL/min per 1.73 m2) or clinically significant renal disease Patients with fasting plasma glucose ≥ 240 mg/dL

Ages Eligible for Study
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Minimum Age: 20 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: DS-8500a 25 mg QD<br>DS-8500a 25 mg tablets, orally, once daily (QD) for up to 28 days | Drug: DS-8500a 25 mg<br> <br> |
| Experimental: DS-8500a 75 mg QD<br>DS-8500a 75 mg tablets, orally, once daily (QD) for up to 28 days | Drug: DS-8500a 75 mg<br> <br> |
| Placebo Comparator: placebo<br>placebo tablets, orally, once daily for up to 28 days | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in 24 hour weighted mean glucose |  | baseline (Day -1) to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in fasting plasma glucose |  | baseline (Day -1) to Day 28 | 
| change in plasma glucose | Day -1 and Day 28: Before breakfast; 0.5, 1, 2, and 4 hours after starting breakfast; 0.5, 1, 2, and 4 hours after starting lunch before evening meal; 0.5, 1, 2, and 4 hours after starting evening meal | baseline (Day -1) and Day 28 | 
| change in glycoalbumin |  | baseline (Day -1) and Day 28 | 
| change in serum insulin | Day -1 and Day 28: Before breakfast; 0.5, 1, 2, and 4 hours after starting breakfast; 0.5, 1, 2, and 4 hours after starting lunch before evening meal; 0.5, 1, 2, and 4 hours after starting evening meal | baseline (Day -1) and Day 28 | 
| change in proinsulin |  | baseline (Day -1) and Day 28 | 
| change in C-peptide | Before breakfast; 0.5, 1, 2, and 4 hours after starting breakfast | baseline (Day -1) and Day 28 | 
| change in PYY (pancreatic peptide YY3-36) | Before breakfast; 0.5, 1, 2, and 4 hours after starting breakfast | baseline (Day -1) and Day 28 | 
| change in total GLP-1 (Glucagon-like peptide-1) |  | baseline (Day -1) and Day 28 | 
| change in active GLP-1 (Glucagon-like peptide-1) | Before breakfast; 0.5, 1, 2, and 4 hours after starting breakfast | baseline (Day -1) and Day 28 | 
| change in total GIP (Gastric inhibitory polypeptide) | Before breakfast; 0.5, 1, 2, and 4 hours after starting breakfast | baseline (Day -1) and Day 28 | 
| change in total glucagon | Before breakfast; 0.5, 1, 2, and 4 hours after starting breakfast | baseline (Day -1) and Day 28 | 
| change in total total cholesterol |  | baseline (Day -1) to after dosing on Day 28 | 
| change in total HDL (high density lipoprotein) cholesterol |  | baseline (Day -1) to after dosing on Day 28 | 
| change in total LDL (low density lipoprotein) cholesterol |  | baseline (Day -1) to after dosing on Day 28 | 
| change in total triglyceride |  | baseline (Day -1) to after dosing on Day 28 | 
| number and severity of adverse events |  | baseline (Day -1) to after dosing on Day 28 | 
| change in derived plasma glucose AUC | change in pharmacodynamic parameters derived from plasma glucose; AUC0-24h, AUC 0-4h, AUC4-8h, AUC9-13h | baseline (Day -1) to after dosing on Day 28 | 
| change in derived serum insulin AUC | change in pharmacodynamic parameters derived from serum insulin; AUC0-24h, AUC 0-4h, AUC4-8h, AUC9-13h | baseline (Day -1) to after dosing on Day 28 | 
| change in derived C-peptide AUC | change in pharmacodynamic parameters derived from C-peptide; AUC0-4h | baseline (Day -1) to after dosing on Day 28 | 
| change in derived PYY AUC | change in pharmacodynamic parameters derived from PYY; AUC0-4h | baseline (Day -1) to after dosing on Day 28 | 
| change in derived total GLP-1 AUC | change in pharmacodynamic parameters derived from total GLP-1; AUC0-4h | baseline (Day -1) to after dosing on Day 28 | 
| change in derived active GLP-1 AUC | change in pharmacodynamic parameters derived from active GLP-1; AUC0-4h | baseline (Day -1) to after dosing on Day 28 | 
| change in derived total GIP AUC | change in pharmacodynamic parameters derived from total GIP; AUC0-4h | baseline (Day -1) to after dosing on Day 28 | 
| change in derived glucagon AUC | change in pharmacodynamic parameters derived from glucagon; AUC0-4h | baseline (Day -1) to after dosing on Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus, sitagliptin, adult, Phase 2