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Add-on to Thiazolidinedione (TZD) Failures

This study has been completed.
Sponsor:
Collaborator:
Astra Zeneca, Bristol-Myers Squibb
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00683878
First received: May 22, 2008
Last updated: January 3, 2017
Last verified: January 2017
  Purpose
The purpose of this clinical research study is to learn if BMS-512148 (Dapagliflozin) can help reduce the blood sugar levels in subjects with Type 2 Diabetes who are not well controlled on TZD alone. The safety of this treatment will also be studied

Condition Intervention Phase
Type 2 Diabetes
Drug: Dapagliflozin
Drug: Placebo matching Dapagliflozin
Drug: Thiazolidinedione (Pioglitazone)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Combination With Thiazolidinedione Therapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Thiazolidinedione Therapy Alone

Resource links provided by NLM:


Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ]
    HbA1c was measured as percent of hemoglobin by a central laboratory. Data after rescue medication 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, 8, 12, 16, 20, and 24 in the double-blind period.


Secondary Outcome Measures:
  • Adjusted Mean Change From Baseline in 120-minute Post-challenge Plasma Glucose (PPG) (mg/dL) at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. In post oral glucose tolerance test (OGTT), glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. 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. PPG measurements were obtained on Day 1 and week 24 in the double-blind period.

  • Adjusted Mean Change From Baseline in Total Body Weight (kg) at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication 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. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period.

  • Adjusted Mean Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Fasting plasma glucose was measured as milligrams per deciliter(mg/dL) by a central laboratory. 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, 8, 12, 16, 20, and 24 in the double-blind period.

  • Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1C]) <7.0% at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Mean and standard error for percentage of participants were estimated by modified logistic regression model.

  • Adjusted Mean Change From Baseline in Waist Circumference (cm) at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in waist circumference at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication 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. Waist circumference measurements were obtained during the qualification and lead-in periods and on Day 1 and Week 24 of the double-blind period.

  • Adjusted Mean Change From Baseline in Total Body Weight (kg) Among Subjects With Baseline Body Mass Index (BMI) ≥ 27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF]) [ Time Frame: From Baseline to Week 24 ]
    Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted mean change from baseline in total body weight among subjects with baseline body mass index (BMI) ≥ 27 kg/m^2 at Week 24 (or the last postbaseline measurement prior to Week 24 if no Week 24 assessment was available was determined. Data after rescue medication 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. Body weight measurements were obtained during the qualification and lead-in periods and on Day 1 and Weeks 1, 2, 4, 8, 12, 16, 20, and 24 of the double-blind period.


Enrollment: 972
Study Start Date: July 2008
Study Completion Date: June 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Dapagliflozin
Tablets, Oral, 5.0 mg, once daily, up to 48 weeks
Other Name: BMS-512148
Drug: Thiazolidinedione (Pioglitazone)
Tablets, ≥ 30 mg, Once daily, up to 48 weeks
Experimental: Arm 2 Drug: Dapagliflozin
Tablets, Oral, 10.0 mg, once daily, up to 48 weeks
Other Name: BMS-512148
Drug: Thiazolidinedione (Pioglitazone)
Tablets, ≥ 30 mg, Once daily, up to 48 weeks
Placebo Comparator: Arm 3 Drug: Placebo matching Dapagliflozin
Tablets, Oral, 0 mg, once daily, up to 48 weeks
Drug: Thiazolidinedione (Pioglitazone)
Tablets, ≥ 30 mg, Once daily, up to 48 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females, ≥ 18 years old, with type 2 diabetes and with inadequate glycemic control
  • All subjects must have central laboratory pre-randomization A1C ≥ 7.0 and ≤ 10.5%
  • C-peptide ≥ 1.0 ng/mL (0.34 nmol/L)
  • Body Mass Index ≤ 45.0 kg/m²

Exclusion Criteria:

  • AST and /or ALT > 2.5 times the upper limit of normal
  • Serum total bilirubin > 2 mg/dL (34.2 µmol/L)
  • Creatinine kinase > 3.0 times the upper limit of normal
  • Symptoms of severely uncontrolled diabetes
  • Serum creatinine ≥ 2.0 mg/dL
  • Calculated Cr-Clearance < 50 ml/min (calculated by Cockroft-Gault formula)
  • Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases
  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: NCT00683878

  Show 89 Study Locations
Sponsors and Collaborators
AstraZeneca
Astra Zeneca, Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00683878     History of Changes
Other Study ID Numbers: MB102-030
Study First Received: May 22, 2008
Results First Received: October 6, 2016
Last Updated: January 3, 2017

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
2,4-thiazolidinedione
Pioglitazone
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on May 25, 2017