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

Phase 2

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: placebo; Drug: DS-8500a 25 mg; Drug: DS-8500a 75 mg

• Registration Number: NCT02685345
• Lead Sponsor: Daiichi Sankyo Co., Ltd.

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-02-03
• Study First Submitted QC: 2016-02-12
• Study First Posted: 2016-02-18
• Primary Completion: 2016-09
• Study Completion: 2016-10
• Status Verified: 2016-11
• Last Update Submitted: 2019-02-08
• Last Update Posted: 2019-02-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 85

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	placebo tablets, orally, once daily for up to 28 days
DS-8500a 25 mg QD	DS-8500a 25 mg	DS-8500a 25 mg tablets, orally, once daily (QD) for up to 28 days
DS-8500a 75 mg QD	DS-8500a 75 mg	DS-8500a 75 mg tablets, orally, once daily (QD) for up to 28 days

Primary Outcome Measures

Name	Time	Method
change in 24 hour weighted mean glucose	baseline (Day -1) to Day 28

Secondary Outcome Measures

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