Back to results

A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise

Primary Purpose

Type 2 Diabetes

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Dapagliflozin

Dapagliflozin placebo

Metformin

About this trial

This is an interventional treatment trial for Type 2 Diabetes

Eligibility Criteria

18 Years - 77 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria

Males and females, aged 18 to 77 years
Type 2 diabetes with inadequate glycemic control, defined as: Group 1, hemoglobin A1c (HbA1c) ≥7% and ≤10%; Group 2, HbA1c ≥10.1% and ≤12.0%
Drug naive, defined as never having received prescription medications for diabetes, having received prescription medications for diabetes for <24 weeks since the original diagnosis
C-peptide ≥1.0 ng/mL at enrollment
Body Mass Index ≤ 45.0 kg/m^2 at enrollment

Key Exclusion Criteria

Urine albumin:creatinine ratio >1,800 mg/g
Aspartate aminotransferase >3*upper limit of normal (ULN)
Alanine aminotransferase >3*ULN
Serum total bilirubin >2*ULN
Serum creatinine ≥1.5 mg/dL for men; ≥1.4 mg/dLfor women
Calcium value outside of the central laboratory normal reference range
Positive hepatitis B surface antigen
Positive anti-hepatitis C virus antibody
Hemoglobin ≤11 g/dL for men; hemoglobin ≤10 g/dL for women
Creatine kinase >3*ULN
Abnormal free T4 values
History of diabetes insipidus
Symptoms of poorly controlled diabetes, including marked polyuria and polydipsia with greater than 10% weight loss in the 3 months prior to enrollment
History of diabetic ketoacidosis or hyperosmolar nonketotic coma
Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg
Any of the following within 6 months of enrollment: Myocardial infarction, cardiac surgery or revascularization, unstable angina, unstable congestive heart failure (CHF), CHF New York Heart Association Class III or IV status, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia
History of unstable or rapidly progressing renal disease
Conditions of congenital renal glucosuria
Significant hepatic disease, including chronic active hepatitis and/or severe hepatic insufficiency
Documented history of hepatotoxicity with any medication
Documented history of severe hepatobiliary disease
History of hemoglobinopathy, with the exception of sickle cell trait, thalassemia minor, or chronic or recurrent hemolysis
Donation of blood or blood products to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of >400 mL of blood during the 6 weeks prior to enrollment
Malignancy (with the exception of treated basal cell or treated squamous cell carcinoma) within 5 years of enrollment visit
Known immunocompromised status, including individuals who had undergone organ transplantation or who had positive HIV results
Administration of any antidiabetic therapy for more than 14 days (consecutive or not) during the 12 weeks prior to enrollment
Administration of any antidiabetic therapy, other than any previously specified, at any dose, at any time during the 4 weeks prior to enrollment
Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for >4 weeks within 3 months prior to enrollment
History of bariatric surgery or lap-band procedure
Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, and/or phendimetrazine, within 30 days of enrollment

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm Type

Experimental

Arm Label

Group 1: Dapagliflozin, 2.5 mg AM

Group 1: Dapagliflozin, 10 mg AM

Group 1: Dapagliflozin 2.5 mg PM

Group 1: Dapagliflozin, 5 mg PM

Group 1: Dapagliflozin, 10 mg PM

Group 2: Dapagliflozin, 5 mg AM

Group 2: Dapagliflozin, 10 mg AM

Group 1: Dapagliflozin placebo AM & PM

Group 1: Dapaglifozon, 5 mg AM

Arm Description

Participants with hemoglobin A1c (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks.

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks.

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks.

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks.

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks.

Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks.

Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.

Outcomes

Primary Outcome Measures

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1C (HbA1c) (Last Observation Carried Forward [LOCF]): Group 1

HbA1c was measured 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Evening dosing groups were summarized as exploratory endpoints.

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) (Last Observation Carried Forward [LOCF]): Group 2

HbA1c was measured 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included.

Secondary Outcome Measures

Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 1

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized in secondary efficacy analyses. Data after rescue medication were 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. If no Week 24 assessment was available, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint.

Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 2

Group 2 was an exploratory group, included to obtain initial efficacy and safety data. No comparator arm was included. Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Data after rescue medication were 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. If no Week 24 assessment was available, glucose levels were recorded from the last postbaseline measurement prior to Week 24. For rescued participants, measurements obtained after initiation of rescue medication was not considered in calculating the endpoint.

Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 1

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. 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.

Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 2

Secondary endpoints were tested using a 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.Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included.

Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 1

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured 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.

Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 2

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured 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.

Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1c] <7.0%) at Week 24 (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Therapeutic glycemic response is defined as HbA1c <7.0%. Data after rescue medication was excluded from this analysis. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) in Patients With Baseline HbA1c ≥9.0% (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. HbA1c was measured as % of hemoglobin by a central laboratory. The population included randomized patients who received treatment and had baseline HbA1c >9.0%. Data after rescue medication were excluded from this analysis. Baseline was defined as the last assessment prior to the start date and time of the first dose of double-blind study drug. In cases where time of the first dose or 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 drug. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered exploratory, included to obtain initial data. No comparator arm was included. Thus, only key safety and efficacy analyses were performed in Group 2.

Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. 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. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Adjusted Percentage of Participants Who Achieved Hemoglobin A1c [HbA1c] ≤6.5% (Last Observation Carried Forward [LOCF])

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Adjusted Mean Change From Baseline to Week 24 in Total Body Weight in Patients With Baseline Body Mass Index ≥27 kg/m^2 (Last Observation Carried Forward)

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. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Number of Participants With Adverse Events (AE), Hypoglycemia, Related AEs, Death as Outcome, Related Serious AEs (SAEs), SAEs and AEs Leading to Discontinuation, and Hypoglycemia Leading to Discontinuation (Short-term + Long-term Periods)

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Related=having certain, probable, possible, or missing relationship to study drug. Includes non-SAEs and hypoglycemia with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term plus long-term treatment plus 4 days. Includes SAEs with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term plus long-term treatment plus 30 days.

Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Laboratory Abnormality (Short-term and Long-term Periods)

Baseline was defined as the last assessment prior to the start of the first dose of the double-blind study medication. Data included from baseline up to and including the last day of treatment plus 4 days. Data after rescue were also included. ULN=upper limit of normal; preRX=pretreatment. Phosphorus, inorganic (high) defined as >=5.6 mg/dL for ages 17-65 years or >=5.1 mg/dL for ages >=66.

Number of Participants With Elevated Levels of Liver Enzymes on Laboratory Test Results (Short-term and Long-term Periods)

Data after rescue was included. AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Findings (Last Observation Carried Forward {LOCF])

12-Lead ECGs were performed at entry into lead-in period Day -7 visit and Week 24/end of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter, and data after rescue were included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Full Information

NCT ID

NCT00528372

First Posted

September 11, 2007

Last Updated

September 30, 2015

Sponsor

AstraZeneca

Collaborators

Bristol-Myers Squibb

1. Study Identification

Unique Protocol Identification Number

NCT00528372

Brief Title

A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise

Official Title

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin as Monotherapy in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control With Diet and Exercise

Study Type

Interventional

2. Study Status

Record Verification Date

September 2015

Overall Recruitment Status

Completed

Study Start Date

September 2007 (undefined)

Primary Completion Date

February 2009 (Actual)

Study Completion Date

July 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this clinical research study is to determine whether dapagliflozin can improve (decrease) blood glucose values in patients with Type 2 diabetes who have never been treated with medication or have been taking medication for less than 24 weeks since their original diabetes diagnosis. The safety of this treatment will also be studied.

Detailed Description

All eligible participants will receive single-blind placebo medication during the 2-week lead-in period. All participants may receive additional open-label treatment with metformin, 500-2000 mg, as needed for rescue, based on protocol specific criteria.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 2 Diabetes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

1067 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Group 1: Dapagliflozin, 2.5 mg AM

Arm Type

Experimental

Arm Description

Participants with hemoglobin A1c (HbA1c) ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each morning for up to 102 weeks.

Arm Title

Group 1: Dapagliflozin, 10 mg AM

Arm Type

Experimental

Arm Description

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each morning for up to 102 weeks.

Arm Title

Group 1: Dapagliflozin 2.5 mg PM

Arm Type

Experimental

Arm Description

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 2.5 mg, once each evening for up to 102 weeks.

Arm Title

Group 1: Dapagliflozin, 5 mg PM

Arm Type

Experimental

Arm Description

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each evening for up to 102 weeks.

Arm Title

Group 1: Dapagliflozin, 10 mg PM

Arm Type

Experimental

Arm Description

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 10 mg, once each evening for up to 102 weeks.

Arm Title

Group 2: Dapagliflozin, 5 mg AM

Arm Type

Experimental

Arm Description

Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.

Arm Title

Group 2: Dapagliflozin, 10 mg AM

Arm Type

Experimental

Arm Description

Participants with HbA1c ≥10.1% and ≤12% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.

Arm Title

Group 1: Dapagliflozin placebo AM & PM

Arm Type

Experimental

Arm Description

Participants with HbA1c ≥7% and ≤10% at enrollment received dapagliflozin placebo once each morning and evening for up to 102 weeks.

Arm Title

Group 1: Dapaglifozon, 5 mg AM

Arm Type

Experimental

Arm Description

Participants with (HbA1c ≥7% and ≤10% at enrollment received dapagliflozin tablets, 5 mg, once each morning for up to 102 weeks.

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin

Other Intervention Name(s)

BMS-512148

Intervention Description

Tablets; oral; 2.5, 5.0, or 10 mg; once daily in the morning or evening for up to 102 weeks

Intervention Type

Drug

Intervention Name(s)

Dapagliflozin placebo

Intervention Description

Tablets, oral, 0 mg, once daily in the morning or evening for up to 102 weeks

Intervention Type

Drug

Intervention Name(s)

Metformin

Other Intervention Name(s)

Tablets, 500-2000 mg, orally as needed in any arm for rescue, based on protocol specific criteria

Primary Outcome Measure Information:

Title

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1C (HbA1c) (Last Observation Carried Forward [LOCF]): Group 1

Description

Time Frame

Baseline to Week 24 (end of Short-term Period)

Title

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) (Last Observation Carried Forward [LOCF]): Group 2

Description

HbA1c was measured 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. If no Week 24 assessment was available, the last postbaseline measurement prior to Week 24 was used. For rescued participants, measurements obtained after initiation of rescue medication were not considered in calculating the primary endpoint. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included.

Time Frame

Baseline to Week 24 (end of Short-term Period)

Secondary Outcome Measure Information:

Title

Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 1

Description

Time Frame

Baseline to Week 24 (end of Short-term Period)

Title

Adjusted Mean Change From Baseline to Week 24 in Fasting Plasma Glucose Levels (Last Observation Carried Forward [LOCF]): Group 2

Description

Time Frame

Baseline to Week 24 (end of Short-term Period)

Title

Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 1

Description

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. 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.

Time Frame

From Baseline to Week 24 (end of Short-term Period)

Title

Adjusted Mean Change in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF]): Group 2

Description

Time Frame

From Baseline to Week 24 (end of Short-term Period)

Title

Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 1

Description

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured 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.

Time Frame

Baseline to Week 1 (end of Short-term Period)

Title

Adjusted Mean Change From Baseline in Fasting Plasma Glucose Levels at Week 1 (Last Observation Carried Forward [LOCF]): Group 2

Description

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. Because the primary focus of the entire dapagliflozin program was on morning dosing in a population with HbA1c ≥7% and ≤10%, only data on AM dosing were summarized. Data after rescue medication was excluded from this analysis. Fasting plasma glucose was measured 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.

Time Frame

Baseline to Week 1

Title

Adjusted Percentage of Participants Achieving a Therapeutic Glycemic Response (Hemoglobin A1c [HbA1c] <7.0%) at Week 24 (Last Observation Carried Forward [LOCF])

Description

Time Frame

Baseline to Week 24 (end of Short-term Period)

Title

Adjusted Mean Change From Baseline to Week 24 in Hemoglobin A1c (HbA1c) in Patients With Baseline HbA1c ≥9.0% (Last Observation Carried Forward [LOCF])

Description

Time Frame

Baseline to Week 24 (end of Short-term Period)

Title

Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) ≥27 kg/m^2 (Last Observation Carried Forward [LOCF])

Description

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. 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. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Time Frame

Baseline to Week 24 (end of Short-term Period)

Title

Adjusted Percentage of Participants Who Achieved Hemoglobin A1c [HbA1c] ≤6.5% (Last Observation Carried Forward [LOCF])

Description

Secondary endpoints were tested using a sequential testing procedure and are presented in hierarchical order. If no Week 24 assessment was available, HbA1c was recorded from the last postbaseline measurement prior to Week 24. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin. Group 2 (patients with enrollment baseline HbA1c >10% and ≤2%) was considered an exploratory group, included to obtain initial efficacy and safety data for these patients. No comparator arm was included. Thus, only key safety and efficacy analyses were performed for Group 2.

Time Frame

Baseline to Week 24 (end of Short-term Period)

Title

Adjusted Mean Change From Baseline to Week 24 in Total Body Weight in Patients With Baseline Body Mass Index ≥27 kg/m^2 (Last Observation Carried Forward)

Description

Time Frame

Baseline to Week 24 (end of Short-term Period)

Title

Description

Time Frame

Day 1 to Week 102 (end of Long-term Period) + 30 days

Title

Number of Participants With Laboratory Test Results Meeting the Criteria for Marked Laboratory Abnormality (Short-term and Long-term Periods)

Description

Time Frame

Baseline to Week 102 (end of Long-term Period)

Title

Number of Participants With Elevated Levels of Liver Enzymes on Laboratory Test Results (Short-term and Long-term Periods)

Description

Time Frame

Day 1 to Week 102 (end of Long-term Period)

Title

Number of Participants With Changes From Baseline in Electrocardiogram (ECG) Findings (Last Observation Carried Forward {LOCF])

Description

Time Frame

Baseline to Week 24 (end of Short-term Period)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

77 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria Males and females, aged 18 to 77 years Type 2 diabetes with inadequate glycemic control, defined as: Group 1, hemoglobin A1c (HbA1c) ≥7% and ≤10%; Group 2, HbA1c ≥10.1% and ≤12.0% Drug naive, defined as never having received prescription medications for diabetes, having received prescription medications for diabetes for <24 weeks since the original diagnosis C-peptide ≥1.0 ng/mL at enrollment Body Mass Index ≤ 45.0 kg/m^2 at enrollment Key Exclusion Criteria Urine albumin:creatinine ratio >1,800 mg/g Aspartate aminotransferase >3*upper limit of normal (ULN) Alanine aminotransferase >3*ULN Serum total bilirubin >2*ULN Serum creatinine ≥1.5 mg/dL for men; ≥1.4 mg/dLfor women Calcium value outside of the central laboratory normal reference range Positive hepatitis B surface antigen Positive anti-hepatitis C virus antibody Hemoglobin ≤11 g/dL for men; hemoglobin ≤10 g/dL for women Creatine kinase >3*ULN Abnormal free T4 values History of diabetes insipidus Symptoms of poorly controlled diabetes, including marked polyuria and polydipsia with greater than 10% weight loss in the 3 months prior to enrollment History of diabetic ketoacidosis or hyperosmolar nonketotic coma Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg Any of the following within 6 months of enrollment: Myocardial infarction, cardiac surgery or revascularization, unstable angina, unstable congestive heart failure (CHF), CHF New York Heart Association Class III or IV status, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia History of unstable or rapidly progressing renal disease Conditions of congenital renal glucosuria Significant hepatic disease, including chronic active hepatitis and/or severe hepatic insufficiency Documented history of hepatotoxicity with any medication Documented history of severe hepatobiliary disease History of hemoglobinopathy, with the exception of sickle cell trait, thalassemia minor, or chronic or recurrent hemolysis Donation of blood or blood products to a blood bank, blood transfusion, or participation in a clinical study requiring withdrawal of >400 mL of blood during the 6 weeks prior to enrollment Malignancy (with the exception of treated basal cell or treated squamous cell carcinoma) within 5 years of enrollment visit Known immunocompromised status, including individuals who had undergone organ transplantation or who had positive HIV results Administration of any antidiabetic therapy for more than 14 days (consecutive or not) during the 12 weeks prior to enrollment Administration of any antidiabetic therapy, other than any previously specified, at any dose, at any time during the 4 weeks prior to enrollment Replacement or chronic systemic corticosteroid therapy, defined as any dose of systemic corticosteroid taken for >4 weeks within 3 months prior to enrollment History of bariatric surgery or lap-band procedure Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, and/or phendimetrazine, within 30 days of enrollment

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Anna Maria Langkilde

Organizational Affiliation

AstraZeneca

Official's Role

Study Director

Facility Information:

Facility Name

43rd Medical Associates, P.C.

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85051

Country

United States

Facility Name

Clin Res Advantage, Inc/East Valley Family Physicians, Plc

City

Tempe

State/Province

Arizona

ZIP/Postal Code

85282

Country

United States

Facility Name

Clinical Research Advantage, Inc

City

Tempe

State/Province

Arizona

ZIP/Postal Code

85282

Country

United States

Facility Name

Valley Research

City

Fresno

State/Province

California

ZIP/Postal Code

93720

Country

United States

Facility Name

Cherlin, Richard

City

Los Gatos

State/Province

California

ZIP/Postal Code

95032

Country

United States

Facility Name

Ritchken & First M.D.'S

City

San Diego

State/Province

California

ZIP/Postal Code

92117

Country

United States

Facility Name

Torrance Clinical Research

City

Torrance

State/Province

California

ZIP/Postal Code

90717

Country

United States

Facility Name

Aurora Family Medicine Center, P.C.

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80012

Country

United States

Facility Name

Expresscare Clinical Research

City

Colorado Springs

State/Province

Colorado

ZIP/Postal Code

80909

Country

United States

Facility Name

Center For Internal Medicine

City

Denver

State/Province

Colorado

ZIP/Postal Code

80209

Country

United States

Facility Name

Denver Internal Medicine Group

City

Denver

State/Province

Colorado

ZIP/Postal Code

80209

Country

United States

Facility Name

Central Florida Clinical Trials

City

Altamonte Springs

State/Province

Florida

ZIP/Postal Code

32701

Country

United States

Facility Name

Family Care Associates

City

Chipley

State/Province

Florida

ZIP/Postal Code

32428

Country

United States

Facility Name

Westside Center For Clinical Research

City

Jacksonville

State/Province

Florida

ZIP/Postal Code

32205

Country

United States

Facility Name

Panhandle Family Care Associates

City

Marianna

State/Province

Florida

ZIP/Postal Code

32446

Country

United States

Facility Name

Louisiana Heart Center

City

Slidell

State/Province

Louisiana

ZIP/Postal Code

70458

Country

United States

Facility Name

Jackson, Danny W.

City

Rolling Fork

State/Province

Mississippi

ZIP/Postal Code

39159

Country

United States

Facility Name

Woodlake Research

City

Chesterfield

State/Province

Missouri

ZIP/Postal Code

63017

Country

United States

Facility Name

Nevada Alliance Against Diabetes

City

Las Vegas

State/Province

Nevada

ZIP/Postal Code

89101

Country

United States

Facility Name

Slocum-Dickson Medical Group, Pllc

City

New Hartford

State/Province

New York

ZIP/Postal Code

13413

Country

United States

Facility Name

Internist Associates Of Central New York, P. C.

City

Syracuse

State/Province

New York

ZIP/Postal Code

13210

Country

United States

Facility Name

Southgate Medical Group

City

West Seneca

State/Province

New York

ZIP/Postal Code

14224

Country

United States

Facility Name

Providence Health Partners

City

Dayton

State/Province

Ohio

ZIP/Postal Code

45439

Country

United States

Facility Name

Newark Physician Associates

City

Newark

State/Province

Ohio

ZIP/Postal Code

43055

Country

United States

Facility Name

Physician Research, Inc.

City

Zanesville

State/Province

Ohio

ZIP/Postal Code

43701

Country

United States

Facility Name

Gilbert Medical Research, Llc

City

Bethany

State/Province

Oklahoma

ZIP/Postal Code

73008

Country

United States

Facility Name

Integris Family Care Yukon

City

Yukon

State/Province

Oklahoma

ZIP/Postal Code

73109

Country

United States

Facility Name

Banksville Medical, Pc

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15216

Country

United States

Facility Name

Southeastern Research Associates, Inc.

City

Taylors

State/Province

South Carolina

ZIP/Postal Code

29687

Country

United States

Facility Name

Holston Medical Group

City

Kingsport

State/Province

Tennessee

ZIP/Postal Code

37660

Country

United States

Facility Name

Village Family Practice

City

Houston

State/Province

Texas

ZIP/Postal Code

77024

Country

United States

Facility Name

Abbott Clinical Research Group, Inc.

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78224

Country

United States

Facility Name

Sam Clinical Research Center

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Taylor/Wade Medical

City

Bountiful

State/Province

Utah

ZIP/Postal Code

84010

Country

United States

Facility Name

Optimum Clinical Research, Inc.

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84102

Country

United States

Facility Name

J. Lewis Research, Inc

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84121

Country

United States

Facility Name

Tidewater Integrated Medical Research

City

Virginia Beach

State/Province

Virginia

ZIP/Postal Code

23454

Country

United States

Facility Name

William L. Gray, Md

City

Spokane

State/Province

Washington

ZIP/Postal Code

99216

Country

United States

Facility Name

Local Institution

City

Calgary

State/Province

Alberta

ZIP/Postal Code

T2R 0X7

Country

Canada

Facility Name

Local Institution

City

Kelowna

State/Province

British Columbia

ZIP/Postal Code

V1Y 2H4

Country

Canada

Facility Name

Local Institution

City

Winnipeg

State/Province

Manitoba

ZIP/Postal Code

R3E 3P4

Country

Canada

Facility Name

Local Institution

City

Bathurst

State/Province

New Brunswick

ZIP/Postal Code

E2A 4X7

Country

Canada

Facility Name

Local Institution

City

Moncton

State/Province

New Brunswick

ZIP/Postal Code

E1G 1A7

Country

Canada

Facility Name

Local Institution

City

Mount Pearl

State/Province

Newfoundland and Labrador

ZIP/Postal Code

A1N 1W7

Country

Canada

Facility Name

Local Institution

City

St-John

State/Province

Newfoundland and Labrador

ZIP/Postal Code

A1E 2E2

Country

Canada

Facility Name

Local Institution

City

St. John'S

State/Province

Newfoundland and Labrador

ZIP/Postal Code

A1A 3R5

Country

Canada

Facility Name

Local Institution

City

Oakville

State/Province

Ontario

ZIP/Postal Code

L6H 3P1

Country

Canada

Facility Name

Local Institution

City

Sarnia

State/Province

Ontario

ZIP/Postal Code

N7T 4X3

Country

Canada

Facility Name

Local Institution

City

Thornhill

State/Province

Ontario

ZIP/Postal Code

L4J 8L7

Country

Canada

Facility Name

Local Institution

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M4R 2G4

Country

Canada

Facility Name

Local Institution

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M9W 4L6

Country

Canada

Facility Name

Local Institution

City

Charlottetown

State/Province

Prince Edward Island

ZIP/Postal Code

C1A 5Y9

Country

Canada

Facility Name

Local Institution

City

Drummondville

State/Province

Quebec

ZIP/Postal Code

J2B 7T1

Country

Canada

Facility Name

Local Institution

City

Granby

State/Province

Quebec

ZIP/Postal Code

J2G 8Z9

Country

Canada

Facility Name

Local Institution

City

L'Ancienne Lorette

State/Province

Quebec

ZIP/Postal Code

G2E 2X1

Country

Canada

Facility Name

Local Institution

City

Mirabel

State/Province

Quebec

ZIP/Postal Code

J7J 2K8

Country

Canada

Facility Name

Local Institution

City

St-Leonard

State/Province

Quebec

ZIP/Postal Code

H1S 3A9

Country

Canada

Facility Name

Local Institution

City

Saskatoon

State/Province

Saskatchewan

ZIP/Postal Code

S7K 3H3

Country

Canada

Facility Name

Local Institution

City

Saskatoon

State/Province

Saskatchewan

ZIP/Postal Code

S7K 7H9

Country

Canada

Facility Name

Local Institution

City

Tijuana

State/Province

Baja California

ZIP/Postal Code

22320

Country

Mexico

Facility Name

Local Institution

City

Guadalajara

State/Province

Distrito Federal

ZIP/Postal Code

44670

Country

Mexico

Facility Name

Local Institution

City

Mexico, D. F.

State/Province

Distrito Federal

ZIP/Postal Code

06726

Country

Mexico

Facility Name

Local Institution

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44100

Country

Mexico

Facility Name

Local Institution

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44600

Country

Mexico

Facility Name

Local Institution

City

Guadalajara

State/Province

Jalisco

ZIP/Postal Code

44680

Country

Mexico

Facility Name

Local Institution

City

Morelia

State/Province

Michioacan

ZIP/Postal Code

58070

Country

Mexico

Facility Name

Local Institution

City

Monterrey

State/Province

Nuevo Leon

ZIP/Postal Code

64060

Country

Mexico

Facility Name

Local Institution

City

Monterrrey

State/Province

Nuevo Leon

ZIP/Postal Code

64700

Country

Mexico

Facility Name

Local Institution

City

Merida

State/Province

Yucatan

ZIP/Postal Code

97070

Country

Mexico

Facility Name

Local Institution

City

Aguascalientes

ZIP/Postal Code

20230

Country

Mexico

Facility Name

Local Institution

City

Durango

ZIP/Postal Code

34000

Country

Mexico

Facility Name

Local Institution

City

Kursk

ZIP/Postal Code

305035

Country

Russian Federation

Facility Name

Local Institution

City

Moscow

ZIP/Postal Code

115093

Country

Russian Federation

Facility Name

Local Institution

City

Saint-Petersburg

ZIP/Postal Code

191015

Country

Russian Federation

Facility Name

Local Institution

City

Smolensk

ZIP/Postal Code

214019

Country

Russian Federation

Facility Name

Local Institution

City

St. Petersburg

ZIP/Postal Code

195257

Country

Russian Federation

Facility Name

Local Institution

City

St.Petersburg

ZIP/Postal Code

195112

Country

Russian Federation

Facility Name

Local Institution

City

Yaroslaval

ZIP/Postal Code

150003

Country

Russian Federation

12. IPD Sharing Statement

Citations:

PubMed Identifier

20566676

Citation

Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care. 2010 Oct;33(10):2217-24. doi: 10.2337/dc10-0612. Epub 2010 Jun 21.

Results Reference

result

PubMed Identifier

25381876

Citation

Bailey CJ, Morales Villegas EC, Woo V, Tang W, Ptaszynska A, List JF. Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes: a randomized double-blind placebo-controlled 102-week trial. Diabet Med. 2015 Apr;32(4):531-41. doi: 10.1111/dme.12624. Epub 2014 Nov 22.

Results Reference

result

PubMed Identifier

27461213

Citation

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.

Results Reference

derived

PubMed Identifier

26894924

Citation

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.

Results Reference

derived

Links:

URL

http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=3672&filename=MB102013_Clinical_Study_Protocol_Redacted.pdf

Description

MB102013_Clinical_Study_Protocol

Learn more about this trial

A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise

We'll reach out to this number within 24 hrs

A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled With Diet and Exercise

Type 2 Diabetes

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial