Safety and Efficacy of S-707106 in Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control With Metformin Therapy

A Phase 2, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study of S-707106 in Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control With Metformin Therapy

The purpose of this study is to evaluate the safety and efficacy of S-707106 co-administered with metformin in subjects with type 2 diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: S-707106 Dose A; Drug: Placebo A tablet; Drug: Metformin; Drug: S-707106 Dose B; Drug: S-707106 Dose C

Detailed Description

Based on the unmet clinical need for more safe and effective type 2 diabetes mellitus therapies, together with the nonclinical efficacy and safety profile of S-707106, Shionogi USA, Inc. is initiating studies to further assess the efficacy, clinical pharmacology and safety profile of S-707106 in preparation for full clinical development as a novel treatment for type 2 diabetes mellitus. It is anticipated that S-707106 will provide clinicians and patients with a new therapeutic option to treat type 2 diabetes mellitus with potential advantages over existing therapy.

• Study Type: Interventional
• Enrollment (Actual): 218
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77074
      • Juno Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Main Inclusion Criteria:

• Subjects with type 2 diabetes mellitus receiving a stable dose of metformin for the past 3 months (with no other medication for glycemic control) and who are clinically stable as determined by medical history
• Body mass index (BMI) ≥25.0 and <45.0 (kg/m2) using http://www.bmicalculator.org/ as the BMI calculator
• No clinically significant abnormal laboratory tests as determined by the investigator except Hemoglobin A1c level ≥7.5% and ≤11.0% and C peptide level >1.0 ng/mL

Main Exclusion Criteria:

• Type 1 diabetes mellitus or gestational diabetes mellitus within last 6 months
• Use of any medication for glycemic control other than metformin during the past 3 months or thiazolidinediones within the past year
• Congestive heart failure as defined by New York Heart Association class III or IV
• Fasting glucose >270 mg/dL
• Creatinine clearance is <60 mL/minute
• History of myocardial infarction within the past 3 months, history of clinically significant cardiac arrhythmia, clinically significant hypotension or hypertension, or clinically significant abnormal electrocardiogram as determined by the investigator

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: S-707106 Dose A; One S-707106 A tablet + 3 Placebo A tablets	Drug: S-707106 Dose A; One S-707106 A tablet; Drug: Placebo A tablet; Up to 4 Placebo A tablets; Drug: Metformin; The standard of care dose of metformin for each patient
Experimental: S-707106 Dose B; One S-707106 B tablet + 3 Placebo A tablets	Drug: Placebo A tablet; Up to 4 Placebo A tablets; Drug: Metformin; The standard of care dose of metformin for each patient; Drug: S-707106 Dose B; One S-707106 B tablet
Experimental: S-707106 Dose C; S-707106 Dose C = Four S-707106 B tablets	Drug: Metformin; The standard of care dose of metformin for each patient; Drug: S-707106 Dose C; Four S-707106 4 X B tablets
Active Comparator: Metformin; The standard of care dose of metformin for the individual patient + 3 Placebo A tablets	Drug: Placebo A tablet; Up to 4 Placebo A tablets; Drug: Metformin; The standard of care dose of metformin for each patient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline to Week 12 in Hemoglobin A1c (HbA1c)	Hemoglobin A1c	Baseline and at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serial pharmacokinetic (PK) assessments	Serial pharmacokinetic sampling at Visit 6 prior to dosing, at Visit 7 prior to dosing and at 0.5, 1, 2, 3, 4, 6, 8 and 24 hours after dosing, at Visit 8, at Visit 9, and Early Termination Visit	5 days
Sparse pharmacokinetic assessments	Sparse pharmacokinetic sampling at Visit 6 and Visit 7 prior to dosing, at Visit 6 or Visit 7 one additional post-dose sample, at Visit 8, at Visit 9, and Early Termination Visit	5 days
Percent of subjects with Hemoglobin A1c < 7.0% at Week 12	Hemoglobin A1c	12 weeks
Change from Baseline at Week 12 in: Fasting plasma glucose, 1,5-Anhydroglucitol, Fructosamine, Glycoalbumin, C-peptide, Beta-cell function and insulin resistance indices using Homeostatic Model Assessment, and Postprandial glucose test	Fasting plasma glucose, 1,5-Anhydroglucitol, Fructosamine, Glycoalbumin, C-peptide, Beta-cell function and insulin resistance indices using Homeostatic Model Assessment, and Postprandial glucose test	Baseline and at 12 weeks
Safety assessments	Safety will be assessed by monitoring of treatment-emergent adverse events, serious adverse events, treatment-emergent adverse events leading to study drug discontinuation, clinical laboratory evaluations, vital signs, 12-lead electrocardiograms (ECGs), adrenal axis hormones, and treatment-emergent adverse events of hypoglycemia, hyperglycemia, confirmed hypoglycemia or hyperglycemia	5-6 months

Collaborators and Investigators

• Sponsor: Shionogi

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: November 11, 2010
• First Submitted That Met QC Criteria: November 12, 2010
• First Posted (Estimate): November 15, 2010

Study Record Updates

• Last Update Posted (Actual): May 15, 2018
• Last Update Submitted That Met QC Criteria: May 10, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Metformin; Type 2 Diabetes Mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 1010N0921