A 52-Week International, Multi-centre, Randomised, Parrall-group, Double-blind, active-controlled, phase III study with a 52-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin in Combination with Metformin compared with Sulphonylurea in Combination with Metformin in Adult Patients with Type 2 Diabetes who have inadeguate Glycaemic Control on Metformin Therapy Alone - ND

• Register: EUCTR
• Last refreshed on: 21 August 2012
• Main ID: EUCTR2007-005220-33-IT
• Date of registration: 11/04/2008
• Prospective Registration: Yes
• Primary sponsor: ASTRAZENECA
• Public title: A 52-Week International, Multi-centre, Randomised, Parrall-group, Double-blind, active-controlled, phase III study with a 52-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin in Combination with Metformin compared with Sulphonylurea in Combination with Metformin in Adult Patients with Type 2 Diabetes who have inadeguate Glycaemic Control on Metformin Therapy Alone - ND
• Scientific title: A 52-Week International, Multi-centre, Randomised, Parrall-group, Double-blind, active-controlled, phase III study with a 52-week Extension Period to Evaluate the Efficacy and Safety of Dapagliflozin in Combination with Metformin compared with Sulphonylurea in Combination with Metformin in Adult Patients with Type 2 Diabetes who have inadeguate Glycaemic Control on Metformin Therapy Alone - ND
• Date of first enrolment: 26/05/2008
• Target sample size: 1865
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-005220-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

France, Germany, Italy, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of a written informed consent
2. Diagnosed with type 2 diabetes
3. Men or women who are ³18 years of age at time of consenting upon visit 1
4. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study in such manner that the risk of pregnancy is minimized.
WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea ≥12 consecutive months; or women on hormone replacement therapy (HRT) with documented serum follicle stimulating hormone (FSH) level >35mIU/mL).
Even women who are using oral, implanted or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered to be of child bearing potential.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of study medication.
5. Treated with OAD therapy that includes metformin for at least 8 weeks prior to enrolment; NB In addition to metformin patients are only allowed to be on one further OAD and only up to the half maximum dose available. This applies both to the administration of the other OAD as separate drug or as fixed dose combination.
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. Type 1 diabetes, history of diabetic ketoacidosis or hyperosmolar non-ketonic coma, or corticosteroid-induced type 2 diabetes
2. History of diabetes insipidus
3. Symptoms of poorly controlled diabetes that would preclude participation in this trial including, but not limited to, marked polyuria and polydipsia with greater than 10% weight loss during the 3 months prior to enrolment, or other signs and symptoms.
4. History of unstable or rapidly progressing renal disease
5. Known condition of congenital renal glucosuria
6. History of severe hepatobiliary disease or hepatotoxicity with any medication
7. Pregnant or breastfeeding patients
8. Body mass index (BMI) >45.0 kg/m2
9. Insulin therapy within one year of enrolment (with the exception of insulin therapy during a hospitalization or use in gestational diabetes)
10. Previous participation in a clinical trial with dapagliflozin (BMS-512148) and/or with any other SGLT2 inhibitor
11. Treatment with glucocorticoids equivalent to oral prednisolone >10 mg (betametasone >1.2 mg/dexametasone >1.5 mg/hydrocortisone >40 mg)/day within 30 days prior to enrolment; topical or inhaled corticosteroids are allowed
12. History of bariatric surgery
13. Administration of weight loss medication, including but not limited to sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, and/or phendimetrazine, within 30 days prior to enrolment
14. Treatment for Human immunodeficiency virus (HIV)/use of antiviral drugs (delavirdine, indinavir, nelfinavir, ritonavir, saquinavir) and/or known immunocompromised status, including patients who have undergone organ transplantation
15. Intolerance, contraindication or potential allergy to metformin, dapagliflozin, glipizide, or placebo or formulation excepients
16. Congestive heart failure defined as New York Heart Association (NYHA) class III or IV (see Appendix D), unstable congestive heart failure and/or left ventricular ejection fraction of ≤ 40%
17. Significant cardiovascular history within the past 6 months upon visit 1 defined as: myocardial infarction, unstable angina pectoris, transient ischemic attack, unstable or previously undiagnosed arrhythmia, cardiac surgery or revascularization (coronary angioplasty or bypass grafts), or cerebrovascular accident
18. Severe respiratory failure or severe emphysema
19. Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg
20. Patients who, in the judgement of the Investigator, may be at risk for dehydration
21. History of chronic haemolytic anaemia with the exception of sickle cell trait or thalassemia minor
22. History of alcohol abuse or illegal drug abuse within the past 12 months
23. History of malignancy within the last 5 years, excluding successful treatment of basal or squamous cell skin carcinoma
24. Involvement in the planning and conduct of the study (applies to both AstraZeneca and Bristol-Myers Squibb staff or staff at the study centre)
25. Previous enrolment or randomisation to treatment in the present study
26. Participation in a clinical study during the last 90 days prior to visit 1
27. Donation of blood, plasma or platelets within the past 3 months prior to visit 1
28. Suspected or confirmed poor protocol or medication compliance as judged by the investigator


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Type 2 diabetes mellitus
MedDRA version: 9.1 Level: HLT Classification code 10012602 Term: Diabetes mellitus (incl subtypes)

Intervention(s)

Product Name: Dapagliflozina
Pharmaceutical Form: Tablet
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Trade Name: MINIDIAB*40CPR 5MG
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Glipizide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Primary Outcome(s)

Secondary Objective: A hierarchical closed testing procedure will be applied in order to control the type I error rate to support secondary superiority claims of dapagliflozin plus metformin treatment over glipizide plus metformin treatment for the following key secondary objectives:
- To show that dapagliflozin plus metformin reduces body weight compared to glipizide plus metformin after 52 weeks of treatment
- To show that dapagliflozin plus metformin treatment leads to fewer patients with hypoglycaemic events compared to glipizide plus metformin after 52 weeks of treatment

Main Objective: to examine whether, after 52 weeks of oral administration of double-blind treatment, the absolute change from baseline in glycosylated haemoglobin A1c (HbA1c) level with dapagliflozin plus metformin is non-inferior to glipizide (sulphonylurea) plus metformin in patients with type 2 diabetes who have inadequate glycaemic control on 1500 mg/day or higher doses of metformin therapy alone.

Primary end point(s):

Secondary ID(s)

2007-005220-33-GB

D1690C00004