Study to Assess Safety and Pharmacokinetics of Double-Blind S-707106 Alone and in Combination With Open-Label Metformin in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety and pharmacokinetics of double-blind S-707106 alone and in combination with open-label metformin in patients with type 2 diabetes mellitus

Detailed Description
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Safety will be evaluated by monitoring of treatment-emergent adverse events, clinical laboratory evaluations, vital signs, 12-lead electrocardiograms, 24-hour telemetry monitoring, and physical exams. Specific study withdrawal criteria during washout periods of metformin have been established for loss of glycemic control, i.e., glucose monitoring. Pharmacokinetic assessments of monotherapy cohort versus add-on therapy will be performed

Official Title
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A Phase 1b, Randomized, Placebo-Controlled Study to Assess the Safety and Pharmacokinetics of Double-Blind S-707106 Alone and in Combination With Open-Label Metformin in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: S-707106
* Drug: Placebo
* Drug: Metformin, S-707106 plus metformin
* Drug: Metformin, placebo plus metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index range (25.0-38 kg/m2) with type 2 diabetes mellitus receiving stable dose of metformin BID for the previous 60 days for glucose control Patients sterile or agree to use approved method of contraception No clinically significant abnormal tests Hemoglobin A1c level ≤10.5% Exclusion Criteria: History of clinical manifestations of significant metabolic, hepatic, renal, and hematological pulmonary, cardiovascular, gastrointestinal, urological, neurological, or psychiatric disorders other than type 2 diabetes mellitus Uncontrolled diabetes Exclusionary labs - fasting blood sugar, low hemoglobin, elevated liver function tests, positive result for human immunodeficiency virus, hepatitis B surface antigen, and anti-hepatitis C virus Low creatinine clearance History of myocardial infarction within past 90 days or other cardiovascular conditions Prior exposure to S-707106 Treatment with investigational study drug within 30 days of study admission day

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Washout period, S-707106 tablet<br>14-day washout of metformin, followed by S-707106 once daily for 14 days under fed conditions | Drug: S-707106<br>* Tablet, taken once daily with morning meal<br>|
| Placebo Comparator: Washout, placebo<br>14-day washout of metformin followed by placebo for S-707106 once daily for 14 days under fed conditions | Drug: Placebo<br>* Placebo tablet, taken once daily with morning meal<br>|
| Experimental: Maintenance, S-707106 tablet plus metformin<br>14-day maintenance of metformin, followed by S-707106 once daily plus open-label metformin twice daily for 14 days under fed conditions | Drug: Metformin, S-707106 plus metformin<br>* Metformin twice daily maintenance, S-707106 tablet taken once daily with morning meal with metformin dosed twice daily<br>|
| Placebo Comparator: Maintenance, placebo plus metformin<br>14-day maintenance of metformin, followed by placebo for S-707106 once daily plus open-label metformin twice daily for 14 days under fed conditions | Drug: Metformin, placebo plus metformin<br>* Metformin twice daily maintenance, placebo tablet taken once daily with morning meal with metformin twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and pharmacokinetics of multiple-dose oral administration of S-707106 in fed state in patients with type 2 diabetes mellitus | Safety will be evaluated by monitoring of treatment-emergent adverse events, clinical laboratory evaluations, vital signs, 12-lead electrocardiograms, 24-hour telemetry monitoring and physical exams. Pharmacokinetic evaluation of monotherapy cohort versus add-on therapy will be done | Adverse events will be monitored from the time of informed consent through 28 days after the last dose of study treatment. Samples for S-707106 will be collected on Days 1, 7, 10, 12, 13, and 14 | 
| Safety and pharmacokinetics of multiple-dose oral co-administration of S-707106 and metformin in fed state in patients with type 2 diabetes mellitus | Safety will be evaluated by monitoring of treatment-emergent adverse events, clinical laboratory evaluations, vital signs, 12-lead electrocardiograms, 24-hour telemetry monitoring and physical exams. Pharmacokinetic evalaution of monotherapy cohort versus add-on therapy will be done | Adverse events will be monitored from the time of informed consent through 28 days after the last dose of study treatment. Samples for S-707106 collected on Days 7, 10, 12, 13, and 14. Samples for metformin collected on Days -1, 7, 10, 12, 13, and 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of multiple doses of S-707106 on pharmacokinetics of metformin |  | On Day 14 and on day prior to initiation of dosing of S-707106 | 
| The effect of multiple doses of metformin on pharmacokinetics of S-707106 |  | On Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metformin