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

This study has been completed.
Sponsor:
Information provided by:
Shionogi Inc.
ClinicalTrials.gov Identifier:
NCT01154348
First received: June 25, 2010
Last updated: September 13, 2011
Last verified: September 2011
  Purpose

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


Condition Intervention Phase
Type 2 Diabetes Mellitus
Drug: S-707106
Drug: Placebo
Drug: Metformin, S-707106 plus metformin
Drug: Metformin, placebo plus metformin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Shionogi Inc.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • The effect of multiple doses of metformin on pharmacokinetics of S-707106 [ Time Frame: On Day 14 ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: June 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01154348

Locations
United States, Texas
Dennis Ruff, MD
San Antonio, Texas, United States, 78209
Sponsors and Collaborators
Shionogi
Investigators
Study Director: Shionogi Clinical Trials Administrator Clinical Support Help Line Shionogi
  More Information

No publications provided

Responsible Party: Shionogi Clinical Trials Administrator, Shionogi
ClinicalTrials.gov Identifier: NCT01154348     History of Changes
Other Study ID Numbers: 1011N0913
Study First Received: June 25, 2010
Last Updated: September 13, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Shionogi Inc.:
Metformin

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014