A Multicenter, Double-Blind, Placebo-Controlled, Parallel Group, Randomized, Phase III study to Evaluate the Glycemic Efficacy and Renal Safety of dapagliflozin in patients with Type 2 Diabetes Mellitus and Moderate Renal Impairment (CKD 3A) who have Inadequate Glycemic Control
- Conditions
- Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]Type 2 Diabetes Mellitus with Moderate Renal Impairment (CKD 3A)
- Registration Number
- EUCTR2015-000804-24-IT
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 321
1, Female or male aged =18 years and <75 years.
2, History of T2DM for more than 12 months.
3, Inadequate glycemic control, defined as HbA1c =7.0% and =11% measured at Screening. Note that HbA1c will be rechecked at Visit 4, and must then be =7.0 and =10.5% (value from blood sample obtained at Visit 3) for patient to be randomized.
4, Stable anti-diabetic treatment regimen, defined as stable diet and exercise therapy alone or in combination with any or both of the two following alternatives:
•A regimen of any approved oral anti-diabetic medication (except SGLT2-inhibitors) where no dose-changes have occurred during 12 weeks before randomization
•Long acting or intermediate acting insulin and mixed insulin permitted as long as the dose is stable during last 12 weeks before randomization, changes ± 10% are allowed (in relation to number of units at randomization).
5, Renal impairment: CKD 3A
•eGFR* 40 – 65 mL/minute/1.73 m2 at Visit 2 (value from blood sample obtained at Visit 1) to enter the lead-in period.
•eGFR* 45 – 59 mL/minute/1.73 m2 at Visit 4 (average value calculated from the eGFR values at Visit 2 and Visit 3) for randomization.
*according to the re-expressed abbreviated (four-variable) MDRD Study equation, using central laboratory measurements of serum creatinine(sCr). [eGFR (mL/min/1.73m2) = 175 x (standardized sCr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if Black)] [Note: sCr reported in mg/dL]
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 151
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 151
1, Women of childbearing potential (WOCBP) who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period.
2, Women who are pregnant or breastfeeding.
3, Aspartate Aminotransferase (AST) >3X ULN.
4, Alanine Aminotransferase (ALT) >3X ULN.
5, Total Bilirubin (TB) >2 mg/dL (35 µmol/L).
6, Serum Potassium (K) >5.5 meq/L (5.5 mmol/L).
7, Serum Calcium (Ca) <8 mg/dL or > ULN (<1.99 mmol/L or > ULN).
8, Positive for hepatitis B surface antigen.
9, Positive for anti-hepatitis C virus antibody.
10, Hemoglobin =9.0 g/dL (90 g/L).
11, History of diabetes insipidus.
12, Symptoms of poorly controlled diabetes that would preclude participation in this study including but not limited to marked polyuria and polydipsia with greater than 10% weight loss during the three months prior to signing the consent at visit 1, or other signs and symptoms.
13, History of diabetic ketoacidosis or hyperosmolar nonketotic coma.
14, History of =2 major hypoglycemic events in the 3 months prior to enrolment, defined as symptomatic events requiring external assistance due to severe impairment in consciousness or behaviour, with blood glucose level <3.0 mmol/L, <54 mg/dL (plasma glucose level <3.5 mmol/L, <63 mg/dL) and prompt recovery after glucose or glucagon administration.
15, Severe uncontrolled hypertension defined as SBP =180 mmHg and/or DBP =110 mmHg at any visit up to randomization.
17, Any of the following CV/Vascular Diseases within 3 months of prior to signing the consent at visit 1:Myocardial infarction, Cardiac surgery or revascularization (CABG/PTCA), Unstable angina, Unstable heart failure (HF), HF New York Heart Association (NYHA) Class IV,Transient ischemic attack (TIA) or significant cerebrovascular disease, Unstable or previously undiagnosed arrhythmia.
18, History of any biopsy or imaging verifying intercurrent kidney disease (such as glomerular nephritis or sign of renal artery stenosis) other than diabetic nephropathy or diabetic nephropathy with nephrosclerosis.
19, History of renal transplant.
20, Hemodialysis, ultrafiltration therapy, or peritoneal dialysis within 6 months prior to signing the consent at visit 1.
21, Significant hepatic disease, including, but not limited to, chronic active hepatitis and/or severe hepatic insufficiency.
22, Documented history of hepatotoxicity with any medication.
23, Documented history of severe hepatobiliary disease.
24, Malignancy within 5 years of the enrolment visit (with the exception of treated basal cell or treated squamous cell carcinoma).
25, Known immunocompromised status, including but not limited to, individuals who have undergone organ transplantation or who are positive for the human immunodeficiency virus (HIV).
26, History of unexplained microscopic or gross hematuria, or microscopic hematuria at visit 2.
27, Long term treatment with glucocorticoids (two temporary periods of no longer than 10 days each are allowed during the study); topical or inhaled corticosteroids are allowed.
28, A metformin dose which is outside the specified dose range for moderate renal impairment (eGFR 30– 59 mL/minute/1.73m2, MDRD formula) according to local guidelines and investigator’s judgement.
29, Ongoing treatment with any SGLT2-inhibitor at screening.
30, History of bariatric surgery or lap-band procedure.
31, Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, Victoza (liraglutide)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To compare the mean change from baseline in HbA1c between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment in patients with type 2 diabetes and CKD stage 3A.;Secondary Objective: 1, To compare the percent change from baseline in total body weight between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment.<br>2, To compare the change from baseline in fasting plasma glucose (FPG) between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment.<br>3, To compare the change from baseline in seated systolic blood pressure (SBP) between dapagliflozin 10 mg and placebo, after 24 weeks of oral administration of double-blind treatment.<br> ;Primary end point(s): Change from baseline in HbA1c at Week 24;Timepoint(s) of evaluation of this end point: Baseline to end of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1, Percent change from baseline in total body weight at Week 24 <br>2, Change from baseline in FPG at Week 24<br>3, Change from baseline in seated SBP at Week 24;Timepoint(s) of evaluation of this end point: Baseline to the end of treatment