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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: placebo; Drug: DS-8500a 25 mg; Drug: DS-8500a 75 mg

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 Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Osaka
    • Yodogawaku, Osaka, Japan, 565-0853

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DS-8500a 25 mg QD; DS-8500a 25 mg tablets, orally, once daily (QD) for up to 28 days	Drug: DS-8500a 25 mg
Experimental: DS-8500a 75 mg QD; DS-8500a 75 mg tablets, orally, once daily (QD) for up to 28 days	Drug: DS-8500a 75 mg
Placebo Comparator: placebo; placebo tablets, orally, once daily for up to 28 days	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.
• Collaborators: Mediscience Planning, Inc.
• Investigators: Principal Investigator: Yasuo Terauchi, MD, PhD, Yokohama city university

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: February 3, 2016
• First Submitted That Met QC Criteria: February 12, 2016
• First Posted (Estimate): February 18, 2016

Study Record Updates

• Last Update Posted (Actual): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: adult; sitagliptin; Type 2 Diabetes Mellitus; Phase 2
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Firuglipel
• Other Study ID Numbers: DS8500-A-J204

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR