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

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

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.

Study Overview

• Status: Completed
• Conditions: Type2 Diabetes Mellitus
• Intervention / Treatment: Drug: DS-8500a; Drug: placebo; Drug: Sitagliptin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 368
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Japan
  • Osaka
    • Suita-shi, Osaka, Japan
      • Heishinkai Medical Group Incorporated OCROM Clinic

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DS-8500a 25 mg QD; DS-8500a 25 mg tablet once daily (QD), orally, for up to 12 weeks, and matching sitagliptin placebo capsule	Drug: DS-8500a; DS-8500a tablets 25mg, 50mg, 75mg; Drug: placebo; matching DS-8500a tablets and sitagliptin capsules
Experimental: DS-8500a 50 mg QD; DS-8500a 50 mg QD tablet, orally, once daily for up to 12 weeks, and matching sitagliptin placebo capsule	Drug: DS-8500a; DS-8500a tablets 25mg, 50mg, 75mg; Drug: placebo; matching DS-8500a tablets and sitagliptin capsules
Experimental: DS-8500a 75 mg QD; DS-8500a 75 mg QD tablet, orally, once daily for up to 12 weeks, and matching sitagliptin placebo capsule	Drug: DS-8500a; DS-8500a tablets 25mg, 50mg, 75mg; Drug: placebo; matching DS-8500a tablets and sitagliptin capsules
Placebo Comparator: placebo; placebo tablet and placebo capsule, orally, once daily for up to 12 weeks to match DS-8500a and sitagliptin, respectively.	Drug: placebo; matching DS-8500a tablets and sitagliptin capsules
Active Comparator: Sitagliptin; capsule, orally, once daily for up to 12 weeks and matching DS-8500 placebo tablet	Drug: placebo; matching DS-8500a tablets and sitagliptin capsules; Drug: Sitagliptin; capsules; Other Names: Januvia

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo Co., Ltd.

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): September 1, 2016

Study Registration Dates

• First Submitted: December 9, 2015
• First Submitted That Met QC Criteria: December 9, 2015
• First Posted (Estimate): December 11, 2015

Study Record Updates

• Last Update Posted (Actual): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Adult; Type 2 Diabetes Mellitus; Developmental Phase II
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate; Firuglipel
• Other Study ID Numbers: DS8500-A-J203

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