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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: S-707106 Dose A
* Drug: S-707106 Dose B
* Drug: S-707106 Dose C
* Drug: Placebo A tablet
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes Mellitus, Metformin