A Pilot Study of BMS-512148 in Subjects With Type 2 Diabetes

A Pilot Study of the Efficacy and Safety of BMS-512148 on Glycemic Control in Subjects With Type 2 Diabetes Treated Aggressively But Not Controlled on Combination Antihyperglycemic Therapy With Metformin and/or Thiazolidinedione (TZD) and Insulin.

The purpose of this clinical research study is to learn if BMS-512148, added to insulin and one or two anti-diabetes medications (metformin and/or pioglitazone or rosiglitazone), can help reduce the blood sugar levels compared to insulin and one or two anti-diabetes medications (metformin and/or pioglitazone or rosiglitazone) alone, in subjects with type 2 diabetes. The safety of this treatment will also be studied.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • Local Institution
  • New Brunswick
    • Bathurst, New Brunswick, Canada, E2A 4X7
      • Local Institution
  • Quebec
    • Gatineau, Quebec, Canada, J8V 2P5
      • Local Institution
    • Laval, Quebec, Canada, H7T 2P5
      • Local Institution
    • Longueuil, Quebec, Canada, J4N 1L6
      • Local Institution
    • Pointe-Claire, Quebec, Canada, H9R 4S3
      • Local Institution
    • Sherbrooke, Quebec, Canada, J1G 5K2
      • Local Institution
• United States
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Clinic
  • California
    • Fresno, California, United States, 93720
      • Valley Research
    • Greenbrae, California, United States, 94904
      • Bernstein, Richard
  • Florida
    • Jacksonville, Florida, United States, 32205
      • Jacksonville Center for Clinical Research
  • Georgia
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions, Inc.
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Model Clinical Research LLC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • St. Louis, Missouri, United States, 63128
      • St. Louis Center for Clinical Research
  • New York
    • Syracuse, New York, United States, 13210
      • SUNY Upstate Medical University
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Mountain Diabetes and Endocrine Center
  • Ohio
    • Mentor, Ohio, United States, 44060
      • Your Diabetes Endocrine Nutrition Group
  • Texas
    • Dallas, Texas, United States, 75231
      • Research Institute of Dallas, P.A.
    • San Antonio, Texas, United States, 78229
      • Diabetes And Glandular Disease Research Associates, P.A.
  • Washington
    • Renton, Washington, United States, 98055
      • Rainier Clinical Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53209
      • Advanced Healthcare S.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females, 18 to 75 years old, with type 2 diabetes with inadequate glycemic control
• Subjects receiving insulin and metformin and/or a thiazolidinedione
• Body Mass Index <=45.0 kg/m2
• Serum creatinine <1.5 mg/dL for men or <1.4 mg/dL for women
• No overt proteinuria (in subjects with a microalbumin/creatinine ratio ≥300 mg/g, the 24-hour urinary excretion of total protein must be <3 g/24 hrs)

Exclusion Criteria:

• History of type 1 diabetes
• AST and/or ALT >2.5 times the upper limit of normal
• Creatinine kinase ≥3 times the upper limit of normal
• Symptoms of severely uncontrolled diabetes
• History of hypoglycemic unawareness
• Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 20 mg	Drug: Dapagliflozin; Tablets, Oral, once daily, up to 12 weeks; Other Names: BMS-512148
Experimental: Cohort 2 - Arm 1; 10 mg	Drug: Dapagliflozin; Tablets, Oral, once daily, up to 12 weeks; Other Names: BMS-512148
Experimental: Cohort 2 - Arm 2; 20 mg	Drug: Dapagliflozin; Tablets, Oral, once daily, up to 12 weeks; Other Names: BMS-512148
Placebo Comparator: Cohort 2 - Arm 3	Drug: Placebo; Tablets, Oral, 0 mg, once daily, up to 12 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2	HbA1c was measured as percent of hemoglobin by a central laboratory. Data after insulin uptitration was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. HbA1c measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 4, 6, 8, 10, and 12 in the double-blind period.	From Baseline to Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2	Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. Data after insulin uptitration was excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. In cases where time of the first dose or time of the assessment was not available, baseline was defined as the last assessment on or prior to the date of the first dose of the double-blind study medication. FPG measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 6, 8, 10, and 12 in the double-blind period.	From Baseline to Week 12
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2	Therapeutic glycemic response is defined as HbA1c <7.0%. Data after insulin uptitration was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.	From Baseline to Week 12
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <=6.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2	Therapeutic glycemic response is defined as HbA1c <=6.5%. Data after insulin uptitration was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.	From Baseline to Week 12
Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) Decrease From Baseline >= 0.5% at Week 12 (Last Observation Carried Forward [LOCF]) - Cohort 2	Therapeutic glycemic response is defined as HbA1c decrease from baseline >= 0.5% at Week 12. Data after insulin uptitration was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.	From Baseline to Week 12
Adjusted Mean Total Daily Dose of Insulin (TDDI) Change From Baseline at Week 12 (LOCF), Including Data After Up-titration of Insulin) - Cohort 2	Baseline TDDI was reduced by 50% prior to treatment, except 2 subjects. TDDI could be up-titrated according to prespecified criteria at Weeks 4, 6, 8, 10 and 12 in the double-blind period.	From Baseline to Week 12

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Mellander A, Billger M, Johnsson E, Traff AK, Yoshida S, Johnsson K. Hypersensitivity Events, Including Potentially Hypersensitivity-Related Skin Events, with Dapagliflozin in Patients with Type 2 Diabetes Mellitus: A Pooled Analysis. Clin Drug Investig. 2016 Nov;36(11):925-933. doi: 10.1007/s40261-016-0438-3.
• Kohan DE, Fioretto P, Johnsson K, Parikh S, Ptaszynska A, Ying L. The effect of dapagliflozin on renal function in patients with type 2 diabetes. J Nephrol. 2016 Jun;29(3):391-400. doi: 10.1007/s40620-016-0261-1. Epub 2016 Feb 19.
• Wilding JP, Norwood P, T'joen C, Bastien A, List JF, Fiedorek FT. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: applicability of a novel insulin-independent treatment. Diabetes Care. 2009 Sep;32(9):1656-62. doi: 10.2337/dc09-0517. Epub 2009 Jun 15.

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: July 26, 2006
• First Submitted That Met QC Criteria: July 26, 2006
• First Posted (Estimate): July 27, 2006

Study Record Updates

• Last Update Posted (Actual): May 11, 2017
• Last Update Submitted That Met QC Criteria: March 31, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Dapagliflozin
• Other Study ID Numbers: MB102-009