A Phase III Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes Who Are Not Well Controlled on Metformin Alone

Type 2 Diabetes Clinical Trial

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 Metformin in Subjects With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Alone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00528879
• Other study ID #: MB102-014 LT
• Secondary ID: MB102-014
• Status: Completed
• Phase: Phase 3
• First received: September 11, 2007
• Last updated: September 30, 2015
• Start date: September 2007
• Est. completion date: May 2010

Study information

• Verified date: September 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Administración Nacional de Medicamentos Alimentos y Tecnología MédicaBrazil: Ministério da Saúde and Agência Nacional de Vigilância Sanitária (National Health Surveillance Agency)Canada: Health CanadaMexico: Federal Commission for Protection Against Health RisksRussia: Ministry of Public Health and Social Development of Russian Federation and Ethic Committee of Federal Supervision Service for Public Health and Social Affairs
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical research study is to learn whether dapagliflozin can help reduce blood sugar levels in participants with Type 2 diabetes that is not well controlled on metformin alone. The safety of this treatment will also be studied.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 915
• Est. completion date: May 2010
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 77 Years

Eligibility

Key Inclusion Criteria

• Males and females, 18 to 77 years old, with type 2 diabetes and inadequate glycemic control

• Participants who have been receiving metformin at a total daily dose =1500 mg per day for at least 8 weeks

• C-peptide =1.0 ng/mL

• Body mass index =45.0 kg/m^2

• Serum creatinine level <1.50 mg/dL for men or <1.40 mg/dL for women.

Key Exclusion Criteria

• Aspartate aminotransferase and/or alanine aminotransferase level >3.0 times the upper limit of normal

• Serum total bilirubin level >2 mg/dL

• Creatinine kinase level >3 times upper limit of normal

• Symptoms of severely uncontrolled diabetes

• Serum creatinine level =1.50 mg/dL for men or =1.40 mg/dL for women

• Currently unstable or serious cardiovascular, renal, hepatic, hematologic, oncologic, endocrine, psychiatric, or rheumatic diseases

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Dapagliflozin
Tablets administered orally as a 2.5-, 5-, or 10-mg dose once daily for up to 102 weeks
• Placebo
Dapagliflozin-matching placebo administered as tablets orally once daily for up to 102 weeks
• Metformin
Open-label metformin administered as =1500 mg per day for up to 102 weeks

Locations

Country	Name	City	State
Argentina	Local Institution	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Capital Federal	Buenos Aires
Argentina	Local Institution	Ciudad Auton	Buenos Aires
Argentina	Local Institution	Ciudad Auton.	Buenos Aires
Argentina	Local Institution	Cordoba
Argentina	Local Institution	Mar Del Plata	Buenos Aires
Argentina	Local Institution	Villa Carlos Paz	Cordoba
Argentina	Local Institution	Zarate	Buenos Aires
Brazil	Local Institution	Belem	Para
Brazil	Local Institution	Caxias Do Sul	Rio Grande Do Sul
Brazil	Local Institution	Fortaleza	Ceara
Brazil	Local Institution	Itajuba	Minas Gerais
Brazil	Local Institution	Marilia	Sao Paulo
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Porto Alegre	Rio Grande Do Sul
Brazil	Local Institution	Rio De Janeiro
Canada	Local Institution	Bathurst	New Brunswick
Canada	Local Institution	Calgary	Alberta
Canada	Local Institution	Charlottetown	Prince Edward Island
Canada	Local Institution	Drummondville	Quebec
Canada	Local Institution	Granby	Quebec
Canada	Local Institution	Kelowna	British Columbia
Canada	Local Institution	L'Ancienne Lorette	Quebec
Canada	Local Institution	Mirabel	Quebec
Canada	Local Institution	Mount Pearl	Newfoundland and Labrador
Canada	Local Institution	Sarnia	Ontario
Canada	Local Institution	Saskatoon	Saskatchewan
Canada	Local Institution	Saskatoon	Saskatchewan
Canada	Local Institution	St-John	Newfoundland and Labrador
Canada	Local Institution	St-Leonard	Quebec
Canada	Local Institution	Thornhill	Ontario
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Winnipeg	Manitoba
Mexico	Local Institution	Df	Distrito Federal
Mexico	Local Institution	Durango
Mexico	Local Institution	Guadalajara	Distrito Federal
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Guadalajara	Jalisco
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrey	Nuevo Leon
Mexico	Local Institution	Monterrrey	Nuevo Leon
Mexico	Local Institution	Tampico	Tamaulipas
Mexico	Local Institution	Zapopan	Distrito Federal
United States	Central Florida Clinical Trials, Inc.	Altamonte Springs	Florida
United States	Cumberland Valley Endocrinology Center, Llc	Carlisle	Pennsylvania
United States	Woodlake Research	Chesterfield	Missouri
United States	Family Care Associates Of Nw Florida	Chipley	Florida
United States	Express Care Clinical Res	Colorado Springs	Colorado
United States	Denver Internal Medicine	Denver	Colorado
United States	Medical Group Of Encino	Encino	California
United States	Valley Research	Fresno	California
United States	New West Physicians	Golden	Colorado
United States	Texas Center For Drug Development, P.A.	Houston	Texas
United States	Nevada Alliance Against Diabetes	Las Vegas	Nevada
United States	Randall Shue, D.O.	Los Angeles	California
United States	Health Partners Research Foundation	Minneapolis	Minnesota
United States	Diabetes & Endocrinology Consultants, Pc	Morehead City	North Carolina
United States	Newark Physician Associates	Newark	Ohio
United States	Diabetes Medical Center Of California	Northridge	California
United States	Integris Family Care S. Penn	Oklahoma City	Oklahoma
United States	Banksville Medical Pc	Pittsburgh	Pennsylvania
United States	Optimum Clinical Research	Salt Lake City	Utah
United States	Diabetes & Glandular Disease Research Associates, Inc.	San Antonio	Texas
United States	S.A.M. Clinical Research Center	San Antonio	Texas
United States	Ritchken & First M.D.'S	San Diego	California
United States	Office Of Dr. Gray	Spokane	Washington
United States	Encompass Clinical Research	Spring Valley	California
United States	Palmetto Clinical Research	Summerville	South Carolina
United States	Southeastern Research Assoc	Taylors	South Carolina
United States	Clinical Research Advantage / Desert Clinical Res, Llc	Tempe	Arizona
United States	Raikhel, Marina	Torrance	California

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Canada,  Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Adverse Events (AEs), Hypoglycemia Events, Related AEs, Death as Outcome, Serious AEs (SAEs), Related SAEs, SAEs Leading to Discontinuation, AEs Leading to Discontinuation, and Hypoglycemia Events Leading to Discontinuation	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. Events captured from baseline to last dose plus 4 days for AEs and plus 30 days for SAEs during the double-blind 12-week period. Data after rescue included.	From Baseline to end of Long-term Period (Week 102)	Yes
Other	Number of Participants With Laboratory Test Results Meeting the Criteria for Laboratory Abnormality	BUN=blood urea nitrogen; preRX=pretreatment; ULN=upper limit of normal; AST=aspartate aminotransferase; ALT=alanine aminotransferase; ALP=alkaline phosphatase. Phosphorus, inorganic (low): ages 17-65 years, =1.8 mg/dL; ages=66 years, =2.1 mg/dL. Phosphorus, inorganic (high): ages 17-65 years, =5.6 mg/dL; ages=66 years, =5.6 mg/dL. Phosphorus, inorganic (low) =1.8 mg/dL if age 17-65 or =2.1 mg/dL if age =66. Calcium, total (high): =1 mg/dL from ULN and =0.5 mg/dL from preRx value.	Day 1 to Week 102	Yes
Other	Number of Participants With Changes in Baseline in Electrocardiogram Findings at Week 102 (Last Observation Carried Forward [LOCF])	12-Lead electrocardiograms (ECGs) were performed at entry into lead-in period Day -7 visit and Week 24/dnd of treatment visit (LOCF) on participants who were supine. ECGs were assessed by the investigator. Baseline was Day -7 for this parameter. Data after rescue included.The Week 102 value is the last observation, regardless of rescue prior to Week 102 if no Week 102 measurement was available.	Baseline to Week 102	Yes
Other	Mean Changes From Baseline in Seated Systolic Blood Pressure	Blood pressure values were obtained after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. Data after rescue were also included. 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.	From Baseline to Week 102	Yes
Other	Mean Changes From Baseline in Seated Diastolic Blood Pressure	Blood pressure values were obtained after the participant was seated quietly for 5 minutes; at least 8 hours after the last ingestion of caffeine, alcohol, or nicotine; and in the same arm (right or left) consistently through out the study. Data after rescue were also included. 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.	From Baseline to Week 102	Yes
Other	Number of Participants With Orthostatic Hypotension	Orthostatic hypotension was defined as a decrease from supine to standing blood pressure of >20 mm Hg in systolic blood pressure or >10 mm Hg in diastolic blood pressure.	From Baseline to Week 102	Yes
Primary	Adjusted Mean Change From Baseline in Hemoglobin A1C (HbA1c) at Week 24 (Last Observation Carried Forward [LOCF])	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.	From Baseline to Week 24	No
Secondary	Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Data after rescue medication was excluded from this analysis. 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.	From Baseline to Week 24	No
Secondary	Adjusted Mean Change From Baseline in Total Body Weight at Week 24 (Last Observation Carried Forward [LOCF])	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, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period.	From Baseline to Week 24	No
Secondary	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 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.	From Baseline to Week 24	No
Secondary	Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline HbA1c =9.0% at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. HbA1c was measured as percent of hemoglobin by a central laboratory. The population included those randomized participants who received treatment and had a 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 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.	From Baseline to Week 24	No
Secondary	Adjusted Mean Change From Baseline in Total Body Weight at Week 24 in Participants With Baseline Body Mass Index (BMI) =27 kg/m^2 (Last Observation Carried Forward [LOCF])	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, 3, 4, 6, 8, 12, 16, 20, and 24 of the double-blind period.	From Baseline to Week 24	No
Secondary	Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) in Participants With Baseline Body Mass Index (BMI) =27 kg/m^2 at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Adjusted for baseline HbA1c. HbA1c was measured as percent of hemoglobin by a central laboratory. 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.	From Baseline to Week 24	No
Secondary	Adjusted Mean Change From Baseline in Fasting Plasma Glucose at Week 1 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. 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.	From Baseline to Week 1	No
Secondary	Adjusted Percentage of Participants Achieving Hemoglobin A1c (HbA1C) =6.5% at Week 24 (Last Observation Carried Forward [LOCF])	Secondary endpoints were tested using sequential testing procedure and are presented in hierarchical order. Percent adjusted for baseline HbA1c. Data after rescue medication was excluded from this analysis. HbA1c was measured as a percent of hemoglobin.	From Baseline to Week 24	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm