A 16-week, Multicentre, Randomised, Double-Blind, Placebo-ControlledPhase III Study to Evaluate the Safety and Efficacy of Dapagliflozin 2.5 mgBID, 5 mg BID and 10 mg QD Versus Placebo in Patients with Type 2Diabetes Who Are Inadequately Controlled on Metformin-IR Monotherapy

• Conditions: Type 2 Diabetes Mellitis; MedDRA version: 12.1Level: LLTClassification code 10012613Term: Diabetes mellitus non-insulin-dependent

• Registration Number: EUCTR2010-019511-37-DE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-09-15
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 654

Inclusion Criteria

1.Provision of informed consent prior to any study specific procedures
2. Diagnosis of T2DM
3. Men or women age = 18 to =77 years old at time of consenting
4. Current antihyperglycaemic treatment with metformin immediate release
formulation monotherapy =1500mg/day at a stable dose for at least 10 weeks prior
to enrolment. Other treatment with OADs within the 10 weeks prior to enrolment is
not permitted.
5. HbA1c =6.7% and =10.5%, based on central laboratory values from Screening
Visit, and Enrolment Visit 1. Note 1: In the case that Stratum 1 has met its goal for
randomised patients, communication will be sent out to all sites that screening and
enrollment will only continue for patients in Stratum 2 with an HbA1c =7.2% and
=10.5%. For these patients in Stratum 2, randomisation criteria of HbA1c =7.0%
and =10.0% will apply (see also inclusion criterion no. 6, Note 2, below).
6. HbA1c =6.5% and =10.0%, based on central laboratory values obtained at Visit 3,
one week prior to randomisation. Note 2: In the case that Stratum 1 has met its goal
for randomised patients, HbA1c randomisation criteria will change to those
applicable for Stratum 2: HbA1c =7.0% and =10.0%, based on central lab values at
Visit 3, one week prior to randomisation.
7. Women of childbearing potential (WOCBP) who comply with the following:
- Use a highly effective method of birth control (see below) to avoid pregnancy
throughout the study and for up to 4 weeks after the study
- Have a negative urine pregnancy test (minimum sensitivity 25 IU/L or
equivalent units of HCG) within 72 hours prior to the start of study medication
and at each visit
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Diagnosis of Type 1 diabetes mellitus, known diagnosis of Maturity Onset Diabetes
of the Young (MODY) or secondary causes of diabetes mellitus
2. History of diabetic ketoacidosis
3. Symptoms of poorly controlled diabetes including, but not limited to, marked
polyuria, polydipsia, and/or greater than 10% weight loss during the 3 months prior
to enrolment
4. FPG >270 mg/dL (>15 mmol/L)
5. BMI > 45 kg/m2
6. History of bariatric surgery (ie, any surgery to treat obesity; for example, gastric
banding or procedures that involve bypassing or transposing sections of the small
intestine). History of liposuction is allowed.
7. Diabetes insipidus
8. Thyroid-stimulating hormone (TSH) and free T4 values outside normal range. An
abnormal TSH value needs to be followed up with a free T4 test. Patients with
abnormal free T4 values will be excluded. Patients with an elevated TSH and
normal free T4 will be allowed if referred to their family doctor for thyroid
hormone replacement therapy prior to randomization
Kidney disorders
9. Creatinine Clearance: <60 mL/min (calculated by Cockcroft-Gault formula) or a
measured serum creatinine value of =1.5 mg/dL (133 µmol/L) for male patients and
=1.4 mg/dL (124 µmol/L) for female patients

13.Severe hepatic insufficiency and/or significant abnormal liver function defined as
aspartate aminotransferase (AST) >3X upper limit of normal (ULN) and/or alanine
aminotransferase (ALT) >3xULN
14. Total bilirubin (TB) >2.0 mg/dL (>34.2 µmol/L)
15. Positive serologic evidence of current infectious liver disease including Hepatitis B
viral antibody IgM, Hepatitis B surface antigen and Hepatitis C virus antibody
16. History of drug-induced liver enzyme elevations
17. History of severe hepatobiliary disease or hepatotoxicity with any medication

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified