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
Overview
- Phase
- Phase 1
- Intervention
- S-707106
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- Shionogi
- Enrollment
- 34
- Locations
- 1
- Primary Endpoint
- Safety and pharmacokinetics of multiple-dose oral administration of S-707106 in fed state in patients with type 2 diabetes mellitus
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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
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
Investigators
Eligibility Criteria
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
Arms & Interventions
Washout period, S-707106 tablet
14-day washout of metformin, followed by S-707106 once daily for 14 days under fed conditions
Intervention: S-707106
Washout, placebo
14-day washout of metformin followed by placebo for S-707106 once daily for 14 days under fed conditions
Intervention: Placebo
Maintenance, S-707106 tablet plus metformin
14-day maintenance of metformin, followed by S-707106 once daily plus open-label metformin twice daily for 14 days under fed conditions
Intervention: Metformin, S-707106 plus metformin
Maintenance, placebo plus metformin
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
Intervention: Metformin, placebo plus metformin
Outcomes
Primary Outcomes
Safety and pharmacokinetics of multiple-dose oral administration of S-707106 in fed state in patients with type 2 diabetes mellitus
Time Frame: 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 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
Safety and pharmacokinetics of multiple-dose oral co-administration of S-707106 and metformin in fed state in patients with type 2 diabetes mellitus
Time Frame: 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
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
Secondary Outcomes
- 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)