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

Phase 2

Completed

Interventions: Drug: S-707106 Dose A
Drug: S-707106 Dose B
Drug: S-707106 Dose C
Drug: Placebo A tablet
Drug: Metformin

Brief Summary: 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.

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
S-707106 Dose B	Placebo A tablet	One S-707106 B tablet + 3 Placebo A tablets
S-707106 Dose A	S-707106 Dose A	One S-707106 A tablet + 3 Placebo A tablets
S-707106 Dose B	S-707106 Dose B	One S-707106 B tablet + 3 Placebo A tablets
S-707106 Dose A	Placebo A tablet	One S-707106 A tablet + 3 Placebo A tablets
S-707106 Dose C	S-707106 Dose C	S-707106 Dose C = Four S-707106 B tablets
Metformin	Placebo A tablet	The standard of care dose of metformin for the individual patient + 3 Placebo A tablets
S-707106 Dose A	Metformin	One S-707106 A tablet + 3 Placebo A tablets
S-707106 Dose B	Metformin	One S-707106 B tablet + 3 Placebo A tablets
S-707106 Dose C	Metformin	S-707106 Dose C = Four S-707106 B tablets
Metformin	Metformin	The standard of care dose of metformin for the individual patient + 3 Placebo A tablets

Primary Outcome Measures

Name	Time	Method
Change from Baseline to Week 12 in Hemoglobin A1c (HbA1c)	Baseline and at 12 weeks	Hemoglobin A1c

Secondary Outcome Measures

Name	Time	Method
Sparse pharmacokinetic assessments	5 days	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
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	Baseline and at 12 weeks	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
Safety assessments	5-6 months	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
Serial pharmacokinetic (PK) assessments	5 days	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
Percent of subjects with Hemoglobin A1c < 7.0% at Week 12	12 weeks	Hemoglobin A1c