12-Week Study of DS-8500a in Subjects With Type 2 Diabetes Mellitus on Metformin

A Randomized, Double-Blind, Placebo-Controlled With Active Comparator, 12-Week Study of DS-8500a in Subjects With Type 2 Diabetes Mellitus on Metformin

The hypothesis of this Phase 2, 12-week study, is that DS-8500a will improve glycemic control relative to placebo, based on changes in HbA1c, with acceptable safety and tolerability, in patients with Type 2 Diabetes Mellitus (T2DM) who are treated with metformin.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: DS-8500a 25mg; Drug: Placebo Tablet; Drug: Placebo Capsule; Drug: Sitagliptin 100 mg

• Study Type: Interventional
• Enrollment (Actual): 298
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1W 4R4
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 4A1
  • Ontario
    • Brampton, Ontario, Canada, L6T 0G1
    • London, Ontario, Canada, N5W 6A2
    • Newmarket, Ontario, Canada, L3Y 5GB
    • Toronto, Ontario, Canada, M9W 4L6
    • Toronto, Ontario, Canada, M9V 4B4
  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
    • Montreal, Quebec, Canada, H4N 2W2
    • Sherbrooke, Quebec, Canada, J1H 1Z1
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
  • Arizona
    • Litchfield Park, Arizona, United States, 85340
    • Tempe, Arizona, United States, 85282
  • California
    • Anaheim, California, United States, 92801
    • Chino, California, United States, 91710
    • Chula Vista, California, United States, 91911
    • Fresno, California, United States, 93720
    • Gold River, California, United States, 95670
    • Greenbrae, California, United States, 94904
    • San Diego, California, United States, 92103
  • Colorado
    • Colorado Springs, Colorado, United States, 80920
    • Lakewood, Colorado, United States, 80227
  • Florida
    • Hallandale Beach, Florida, United States, 33009
    • Miami, Florida, United States, 33126
    • Miami, Florida, United States, 33135
    • Pembroke Pines, Florida, United States, 33026
    • West Palm Beach, Florida, United States, 33409
  • Georgia
    • Atlanta, Georgia, United States, 30331
  • Idaho
    • Boise, Idaho, United States, 83704
  • Indiana
    • Avon, Indiana, United States, 46123
    • Evansville, Indiana, United States, 47725
    • Franklin, Indiana, United States, 46131
    • Greenfield, Indiana, United States, 46140
  • Iowa
    • Council Bluffs, Iowa, United States, 51503
  • Michigan
    • Troy, Michigan, United States, 48098
  • Minnesota
    • Edina, Minnesota, United States, 55435
  • Missouri
    • Washington, Missouri, United States, 63090
  • Nebraska
    • Omaha, Nebraska, United States, 68114
  • North Carolina
    • Mooresville, North Carolina, United States, 28117
    • Morgantown, North Carolina, United States, 28655
    • Winston-Salem, North Carolina, United States, 27103
  • Ohio
    • Columbus, Ohio, United States, 43213
  • Oregon
    • Medford, Oregon, United States, 97504
  • South Carolina
    • Charleston, South Carolina, United States, 29425
    • Charleston, South Carolina, United States, 29407
    • Greer, South Carolina, United States, 29651
    • Mount Pleasant, South Carolina, United States, 29464
    • Spartanburg, South Carolina, United States, 29303
  • Texas
    • Austin, Texas, United States, 78705
    • Dallas, Texas, United States, 75231
    • Houston, Texas, United States, 77036
    • Plano, Texas, United States, 75024
    • San Antonio, Texas, United States, 78229
    • San Antonio, Texas, United States, 78228
  • Utah
    • Salt Lake City, Utah, United States, 84121
    • Salt Lake City, Utah, United States, 84102
    • South Jordan, Utah, United States, 84095
  • Virginia
    • Burke, Virginia, United States, 22015

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to provide written informed consent and adhere to the study visit schedule and treatment
• Diagnosed with Type 2 diabetes mellitus as defined in the American Diabetes Association Standards of Medical Care in Diabetes 2015
• Male or female ≥ 18 and ≤ 70 years of age
• Screening fasting C-peptide > 0.5 ng/mL
• Women of child bearing potential (WOCBP) must be willing to use double-barrier contraception for the entire study
• WOCBP must have a negative pregnancy test (human chorionic gonadotropin, beta subunit [βhCG]) before entering the Lead-in Period
• Body mass index ≥ 25 kg/m2 and ≤ 45 kg/m2 at the Screening Visit
• On stable (≥ 8 weeks) metformin monotherapy ≥ 1000 mg/day
• Screening HbA1c ≥ 7.0% and ≤ 10%
• Taking ≥ 80% and ≤ 120% of both dispensed DS-8500a placebo tablets and sitagliptin placebo capsules during the Lead-in Period

Exclusion Criteria:

• History of type 1 diabetes and/or history of ketoacidosis
• History of insulin use for > 2 weeks within 2 months prior to the Screening Visit
• Two or more readings of fasting Self-monitoring of Blood Glucose (SMBG) > 240 mg/dL or worsening symptoms of hyperglycemia with one SMBG level of > 240 mg/dL during the second week of Lead-in Period, confirmed by laboratory measurement
• Screening hemoglobin <12 g/dL for males and <11 g/dL for females
• Blood donation within 2 months prior to the Screening Visit or plans to donate blood or blood products during the study
• Subjects after bariatric surgery or any gastric bypass
• Screening thyroid stimulating hormone (TSH) levels not within normal range (based on reference laboratory values )
• Screening Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 2.0 x upper limit of normal (ULN), and/or total bilirubin > 1.5 x ULN. If a subject has total bilirubin > 1.5 ULN, unconjugated and conjugated bilirubin fractions should be analyzed and only subjects documented to have Gilbert's syndrome may be enrolled
• Screening Serum creatinine ≥ 1.5 mg/dL for males and ≥ 1.4 mg/dL for females, or creatinine clearance (CrCl) < 50 mL/min for both males and females
• Screening Creatine kinase (CK) > 3.0 × ULN
• History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, peripheral arterial event or any revascularization procedure during the 6 months prior to the Screening Visit or planned vascular procedures or surgery during study period
• History of congestive heart failure (CHF)

• Exclusionary concomitant medications:

  a. Eight weeks prior to screening and throughout the duration of the study:

• Any diabetes medication other than metformin; any prescription or over the counter medication for weight-loss.
• Systemic corticosteroids (including nasal and inhaled), with the exception of use of topical and ophthalmic corticosteroids.
• Rosuvastatin > 20 mg daily. b. During treatment periods, additional medications will be prohibited based on potential drug-drug interaction (DDI) (see Section 5.6)
• Subjects with anticipated interruption in metformin or study drug use during the course of the clinical trial (e.g., due to an imaging procedure involving iodinated contrast media)
• Subjects in whom treatment with sitagliptin 100 mg is contraindicated ( e.g., known hypersensitivity or intolerance to sitagliptin) or may not be medically advisable (e.g., history of pancreatitis)
• Abuse of or dependence on prescription medications, illicit drugs, or alcohol within the last 1 year
• Any history of a malignancy other than basal cell carcinoma within the past 5 years
• Pregnancy or breast-feeding, or intent to become pregnant during the study period
• Known (or evidence of) infection with human immunodeficiency virus
• Any condition, laboratory abnormality, or concomitant therapy which, in the opinion of the Investigator, might pose a risk to the subject or make participation not in the subject's best interest
• Subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents
• A direct or familial relationship with the Sponsor, Investigator, or site personnel affiliated with the study

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 25mg; One DS-8500a 25 mg tablet, 2 placebo tablets, and one placebo capsule in a once-daily oral dose	Drug: DS-8500a 25mg; DS-8500a 25mg tablet for oral administration; Other Names: Investigational product; Drug: Placebo Tablet; Placebo matching DS-8500a tablet for oral administration; Other Names: Placebo; Drug: Placebo Capsule; Placebo matching sitagliptin over-capsule for oral administration; Other Names: Placebo
Experimental: DS-8500a 50 mg; Two DS-8500a 25 mg tablets, 1 placebo tablet, and one placebo capsule in a once-daily oral dose	Drug: DS-8500a 25mg; DS-8500a 25mg tablet for oral administration; Other Names: Investigational product; Drug: Placebo Tablet; Placebo matching DS-8500a tablet for oral administration; Other Names: Placebo; Drug: Placebo Capsule; Placebo matching sitagliptin over-capsule for oral administration; Other Names: Placebo
Experimental: DS-8500a 75 mg; Three DS-8500a 25 mg tablets and one placebo capsule in a once-daily oral dose	Drug: DS-8500a 25mg; DS-8500a 25mg tablet for oral administration; Other Names: Investigational product; Drug: Placebo Capsule; Placebo matching sitagliptin over-capsule for oral administration; Other Names: Placebo
Placebo Comparator: Placebo; Three placebo tablets and one placebo capsule in a once-daily oral dose	Drug: Placebo Tablet; Placebo matching DS-8500a tablet for oral administration; Other Names: Placebo; Drug: Placebo Capsule; Placebo matching sitagliptin over-capsule for oral administration; Other Names: Placebo
Active Comparator: Sitagliptin 100 mg; Three placebo tablets and one sitagliptin 100 mg over-capsule in a once-daily oral dose	Drug: Placebo Tablet; Placebo matching DS-8500a tablet for oral administration; Other Names: Placebo; Drug: Sitagliptin 100 mg; Two sitagliptin 50 mg tablets, over-encapsulated to provide a once-daily dose of 100 mg, for oral administration; Other Names: Januvia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12	Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the three-month average glucose concentration in the blood. Target HbA1c for Type 2 diabetics was less than 7% at the time of this trial. Negative scores show improvement from baseline.	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Total Cholesterol (TC) at Week 12	Total cholesterol is a measure of the total amount of cholesterol in the blood, including low-density lipoprotein cholesterol (LDL-C) - the "bad" cholesterol, high-density lipoprotein cholesterol (HDL-C) - the "good" cholesterol, and triglycerides. The equation to calculate total cholesterol is: LDL + HDL + (triglycerides/5) = total cholesterol.	Baseline, Week 12
Change From Baseline in LDL-C at Week 12	LDL-C is known as the "bad" cholesterol, so a lower score (negative change) means improvement.	Baseline, Week 12
Change From Baseline in HDL-C at Week 12	HDL-C is known as the "good" cholesterol, so a higher score (positive change) means improvement.	Baseline, Week 12
Change From Baseline in Non-HDL-C at Week 12	Non-HDL-C is the measure of "bad" cholesterol in the blood, including triglycerides and LDL-C, so a negative change means improvement. The equation for Non-HDL-C = LDL-C + (triglycerides/5).	Baseline, Week 12
Change From Baseline in Triglycerides at Week 12	Triglycerides are a type of fat found in the blood. The body uses them for energy. Some triglycerides are needed for good health. But high triglycerides might raise the risk of heart disease. Since Type 2 diabetics tend to have high triglycerides, a negative change means improvement.	Baseline, Week 12
Change From Baseline in Area-Under-the Curve 0-3 Hours (AUC0-3h) of Plasma Glucose (PG) in Response to the Mixed Meal Tolerance Test (MMTT) at Week 4	The MMTT requires a participant to drink a "mixed meal," such as Boost or Ensure, that contains protein, carbohydrates, and fat. The goal of the test is to find out how much insulin the pancreas makes in response to food by measuring the level of glucose in the blood. The lower the level of glucose in the blood during the first three hours after the test (AUC0-3h), the more insulin the body has made in response to the test. This would mean a negative change shows improvement.	Baseline, Week 4
Change From Baseline in AUC0-3h of PG in Response to the MMTT at Week 12	The MMTT requires a participant to drink a "mixed meal," such as Boost or Ensure, that contains protein, carbohydrates, and fat. The goal of the test is to find out how much insulin the pancreas makes in response to food by measuring the level of glucose in the blood. The lower the level of glucose in the blood during the first three hours after the test (AUC0-3h), the more insulin the body has made in response to the test. This would mean a negative change shows improvement.	Baseline, Week 12
Change From Baseline in Maximum Concentration (Cmax) of PG in Response to MMTT at Week 4	Cmax measures the highest amount of glucose in the blood, so a negative change means improvement.	Baseline, Week 4
Change From Baseline in Cmax of PG in Response to MMTT at Week 12	Cmax measures the highest amount of glucose in the blood, so a negative change means improvement.	Baseline, Week 12
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 2	Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement.	Baseline, Week 2
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4	Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement.	Baseline, Week 4
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 8	Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement.	Baseline, Week 8
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12	Normal fasting plasma glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter (mg/dL) for people who do not have diabetes. People with Type 2 diabetes typically have FPG that is too high, so a negative change from baseline means improvement.	Baseline, Week 12
Count of Participants With HbA1c Less Than 7.0% at Week 12	HbA1C less than 7% is the success goal for many Type 2 diabetics.	Week 12

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): January 31, 2017
• Study Completion (Actual): January 31, 2017

Study Registration Dates

• First Submitted: January 4, 2016
• First Submitted That Met QC Criteria: January 4, 2016
• First Posted (Estimate): January 6, 2016

Study Record Updates

• Last Update Posted (Actual): February 25, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: interventional; type 2 diabetes mellitus; phase 2; double blind
• 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-U202

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; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)