A Phase 2 Study of DS-8500a in Japanese Subjects With Type 2 Diabetes Mellitus (T2DM)

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

Detailed Description
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The objectives of the study is to evaluate the efficacy, safety, and dose of DS-8500a compared with placebo in patients with type 2 diabetes mellitus after a 12-week oral administration of DS-8500a at 25, 50, or 75 mg in a double-blind, parallel-group comparison study. In addition, the clinical positioning of DS-8500a relative to an existing drug will be investigated using sitagliptin as a comparator.

Official Title
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A Phase 2, Randomized, Double-blind, Dose Finding Study of DS-8500a in Japanese Patients With Type 2 Diabetes Mellitus

Conditions
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Type2 Diabetes Mellitus

Intervention / Treatment
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* Drug: DS-8500a
* Drug: Sitagliptin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged ≥ 20 years at the time of informed consent Japanese patients with type 2 diabetes Patients who have HbA1c ≥ 7.0% and < 10.0% 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 tablet once daily (QD), orally, for up to 12 weeks, and matching sitagliptin placebo capsule | Drug: DS-8500a<br>* DS-8500a tablets 25mg, 50mg, 75mg<br>Drug: placebo<br>* matching DS-8500a tablets and sitagliptin capsules<br>|
| Experimental: DS-8500a 50 mg QD<br>DS-8500a 50 mg QD tablet, orally, once daily for up to 12 weeks, and matching sitagliptin placebo capsule | Drug: DS-8500a<br>* DS-8500a tablets 25mg, 50mg, 75mg<br>Drug: placebo<br>* matching DS-8500a tablets and sitagliptin capsules<br>|
| Experimental: DS-8500a 75 mg QD<br>DS-8500a 75 mg QD tablet, orally, once daily for up to 12 weeks, and matching sitagliptin placebo capsule | Drug: DS-8500a<br>* DS-8500a tablets 25mg, 50mg, 75mg<br>Drug: placebo<br>* matching DS-8500a tablets and sitagliptin capsules<br>|
| Placebo Comparator: placebo<br>placebo tablet and placebo capsule, orally, once daily for up to 12 weeks to match DS-8500a and sitagliptin, respectively. | Drug: placebo<br>* matching DS-8500a tablets and sitagliptin capsules<br>|
| Active Comparator: Sitagliptin<br>capsule, orally, once daily for up to 12 weeks and matching DS-8500 placebo tablet | Drug: Sitagliptin<br>* capsules<br>* Other names: Januvia;Drug: placebo<br>* matching DS-8500a tablets and sitagliptin capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in HbA1c | HbA1c = glycated hemoglobin | baseline (Day -1) to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in HbA1c |  | baseline (Day -1) to Week 4 | 
| change in HbA1c |  | baseline (Day -1) to Week 8 | 
| proportion of subjects with HbA1c <7.0 | proportion of subjects who achieve HbA1c <7.0 | baseline (Day -1) to Week 12 | 
| change in plasma glucose |  | baseline (Day -1) to Week 4 | 
| change in plasma glucose |  | baseline (Day -1) to Week 12 | 
| change in AUC derived from plasma glucose | change in pharmacodynamics profile consists of Area Under Curve (AUC), Concentration maximum (Cmax), Time of maximum concentration (Tmax) | baseline (Day -1) to Week 4 | 
| change in AUC derived from plasma glucose | pharmacodynamics profile consists of AUC, Cmax, Tmax | baseline (Day -1) to Week 12 | 
| change in serum insulin |  | baseline (Day -1) to Week 4 | 
| change in AUC 0-3h serum insulin |  | baseline (Day -1) to Week 4 | 
| change in serum insulin |  | baseline (Day -1) to Week 12 | 
| change in AUC 0-3h serum insulin |  | baseline (Day -1) to Week 12 | 
| change in proinsulin |  | baseline (Day -1) to Week 4 | 
| change in AUC 0-3h proinsulin |  | baseline (Day -1) to Week 4 | 
| change in proinsulin |  | baseline (Day -1) to Week 12 | 
| change in AUC 0-3h proinsulin |  | baseline (Day -1) to Week 12 | 
| change in C-peptide |  | baseline (Day -1) to Week 4 | 
| change in AUC 0-3h C-peptide |  | baseline (Day -1) to Week 4 | 
| change in C-peptide |  | baseline (Day -1) to Week 12 | 
| change in AUC 0-3h C-peptide |  | baseline (Day -1) to Week 12 | 
| change in PYY | PYY = peptide YY | baseline (Day -1) to Week 4 | 
| change in AUC 0-3h PYY |  | baseline (Day -1) to Week 4 | 
| change in PYY |  | baseline (Day -1) to Week 12 | 
| change in AUC 0-3h PYY |  | baseline (Day -1) to Week 12 | 
| change in total GLP-1 | GLP-1 = Glucagon-Like Peptide-1 | baseline (Day -1) to Week 4 | 
| change in total AUC 0-3h GLP-1 |  | baseline (Day -1) to Week 4 | 
| change in total GLP-1 |  | baseline (Day -1) to Week 12 | 
| change in AUC 0-3h total GLP-1 |  | baseline (Day -1) to Week 12 | 
| change in active GLP-1 |  | baseline (Day -1) to Week 4 | 
| change in AUC 0-3h active GLP-1 |  | baseline (Day -1) to Week 4 | 
| change in active GLP-1 |  | baseline (Day -1) to Week 12 | 
| change in AUC 0-3h active GLP-1 |  | baseline (Day -1) to Week 12 | 
| change in total GIP | GIP = Gastric Inhibitory Polypeptide | baseline (Day -1) to Week 4 | 
| change in AUC 0-3h total GIP |  | baseline (Day -1) to Week 4 | 
| change in total GIP |  | baseline (Day -1) to Week 12 | 
| change in AUC 0-3h total GIP |  | baseline (Day -1) to Week 12 | 
| change in glucagon |  | baseline (Day -1) to Week 4 | 
| change in AUC 0-3h glucagon |  | baseline (Day -1) to Week 4 | 
| change in glucagon |  | baseline (Day -1) to Week 12 | 
| change in AUC 0-3h glucagon |  | baseline (Day -1) to Week 12 | 
| change in 1,5 AG | 1,5 AG = 1,5 anhydrogucitol | baseline (Day -1) to Week 4 | 
| change in AUC 0-3h 1,5 AG |  | baseline (Day -1) to Week 4 | 
| change in 1,5 AG |  | baseline (Day -1) to Week 12 | 
| change in AUC 0-3h 1,5 AG |  | baseline (Day -1) to Week 12 | 
| change in total cholesterol |  | baseline (Day -1) to Week 2 | 
| change in total cholesterol |  | baseline (Day -1) to Week 4 | 
| change in total cholesterol |  | baseline (Day -1) to Week 8 | 
| change in total cholesterol |  | baseline (Day -1) to Week 12 | 
| change in HDL cholesterol | HDL = high density lipoprotein | baseline (Day -1) to Week 2 | 
| change in HDL cholesterol |  | baseline (Day -1) to Week 4 | 
| change in HDL cholesterol |  | baseline (Day -1) to Week 8 | 
| change in HDL cholesterol |  | baseline (Day -1) to Week 12 | 
| change in LDL cholesterol | LDL = low density lipoprotein | baseline (Day -1) to Week 2 | 
| change in LDL cholesterol |  | baseline (Day -1) to Week 4 | 
| change in LDL cholesterol |  | baseline (Day -1) to Week 8 | 
| change in LDL cholesterol |  | baseline (Day -1) to Week 12 | 
| change in triglyceride |  | baseline (Day -1) to Week 2 | 
| change in triglyceride |  | baseline (Day -1) to Week 4 | 
| change in triglyceride |  | baseline (Day -1) to Week 8 | 
| change in triglyceride |  | baseline (Day -1) to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus, Adult, Developmental Phase II