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

• ClinicalTrials.gov Identifier: NCT01154348
• Recruitment Status: Completed
• First Posted: June 30, 2010
• Last Update Posted: April 27, 2018
• Sponsor: Shionogi
• Information provided by (Responsible Party): Shionogi Inc. ( Shionogi )

Tracking Information

• First Submitted Date: June 25, 2010
• First Posted Date: June 30, 2010
• Last Update Posted Date: April 27, 2018
• Study Start Date: June 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 13, 2011)

• 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

Original Primary Outcome Measures (submitted: June 29, 2010)

• Safety & PK of multiple-dose oral administration of S-707106 in fed state in patients with type 2 diabetes mellitus [ Time Frame: 14-day wash-out/ maintenance , 14-day dosing period, 3-day transition to standard of care ]
  Safety will be evaluated by monitoring of treatment-emergent adverse events (TEAEs), clinical laboratory evaluations, vital signd, 12-lead ECGs, 24-hour telemetry monitoring and physical exams. PK evaluation of monotherapy cohort versus add-on therapy.
• Safety and PK of multiple-dose oral co-administration of S-707106 & metformin in fed state in patients with type 2 diabetes mellitus [ Time Frame: 14-day wash-out / maintenance, 14-day dosing period, 3-day transition to standard of care ]
  Safety will be evaluated by monitoring of treatment-emergent adverse events (TEAEs), clinical laboratory evaluations, vital signs, 12-lead ECGs, 24-hour telmetry monitoring and physical exams. PK evalaution of monotherapy cohort versus add-on therapy.

Current Secondary Outcome Measures (submitted: September 13, 2011)

• The effect of multiple doses of S-707106 on pharmacokinetics of metformin [ Time Frame: 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 [ Time Frame: On Day 14 ]

Original Secondary Outcome Measures (submitted: June 29, 2010)

• The effect of multiple doses of S-707106 on PK of metformin [ Time Frame: 14-day wash-out/ maintenance, 14-day dosing period, 3-day transition to standard of care ]
• The effect of multiple doses of metformin on PK of S-707106 [ Time Frame: 14-day wash-out/ maintenance, 14-day dosing period, 3-day transition to standard of care ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• 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
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Type 2 Diabetes Mellitus

Intervention

• Drug: S-707106
  Tablet, taken once daily with morning meal
• Drug: Placebo
  Placebo tablet, taken once daily with morning meal
• Drug: Metformin, S-707106 plus metformin
  Metformin twice daily maintenance, S-707106 tablet taken once daily with morning meal with metformin dosed twice daily
• Drug: Metformin, placebo plus metformin
  Metformin twice daily maintenance, placebo tablet taken once daily with morning meal with metformin twice daily

Study Arms

• Experimental: Washout period, S-707106 tablet
  14-day washout of metformin, followed by S-707106 once daily for 14 days under fed conditions
  Intervention: Drug: S-707106
• Placebo Comparator: Washout, placebo
  14-day washout of metformin followed by placebo for S-707106 once daily for 14 days under fed conditions
  Intervention: Drug: Placebo
• 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
  Intervention: Drug: Metformin, S-707106 plus metformin
• 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
  Intervention: Drug: Metformin, placebo plus metformin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 29, 2010): 34
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: December 2010
• Actual Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01154348
• Other Study ID Numbers: 1011N0913
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Shionogi Inc. ( Shionogi )
• Study Sponsor: Shionogi
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Shionogi Inc.
• Verification Date: April 2018