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

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

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: S-707106; Drug: Placebo; Drug: Metformin, S-707106 plus metformin; Drug: Metformin, placebo plus metformin

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

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78209
      • Dennis Ruff, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Washout period, S-707106 tablet; 14-day washout of metformin, followed by S-707106 once daily for 14 days under fed conditions	Drug: S-707106; Tablet, taken once daily with morning meal
PLACEBO_COMPARATOR: Washout, placebo; 14-day washout of metformin followed by placebo for S-707106 once daily for 14 days under fed conditions	Drug: Placebo; Placebo tablet, taken once daily with morning meal
EXPERIMENTAL: 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	Drug: Metformin, S-707106 plus metformin; Metformin twice daily maintenance, S-707106 tablet taken once daily with morning meal with metformin dosed twice daily
PLACEBO_COMPARATOR: 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	Drug: Metformin, placebo plus metformin; Metformin twice daily maintenance, placebo tablet taken once daily with morning meal with metformin twice daily

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Shionogi

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (ACTUAL): November 1, 2010
• Study Completion (ACTUAL): December 1, 2010

Study Registration Dates

• First Submitted: June 25, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (ESTIMATE): June 30, 2010

Study Record Updates

• Last Update Posted (ACTUAL): April 27, 2018
• Last Update Submitted That Met QC Criteria: April 25, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Metformin
• 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: 1011N0913