A study to examine whether the glucose lowering medicine dapagliflozin decreases urinary protein excretion and to determine the variation in response to dapagliflozin in plasma glucose / urinary protein excretion / blood pressure between and within patients.

Conditions: Patients with type 2 diabetes and albuminuria between 100 and 3500 mg/g.
Therapeutic area: Diseases [C] - Hormonal diseases [C19]

Registration Number: EUCTR2014-000157-37-NL

Lead Sponsor: niversity Medical Center Groningen

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

•Age =18 and =75 years
•Diagnosis of type 2 diabetes mellitus
•HbA1c = 6.6% and <11.0%
•Urinary albumin excretion > 100 mg/g
•On a stable dose of an ACEi or ARB for at least 4 weeks prior to randomization
•On a stable dose of blood glucose lowering medication for at least 4 weeks prior to randomization
•eGFR = 45 mL/min/1.73m2
•Willing to sign informed consent
•Women of Child-Bearing Potential (WOCBP):
oWOCBP must be using an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug in such a manner that the risk of pregnancy is minimized.
oWOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent units of HCG) within 0 to 72 hours before the first dose of study drug.
oWomen must not be breast-feeding.
WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal (see definition below). The following women are WOCBP:
oWomen using the following methods to prevent pregnancy: Oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as intrauterine devices or barrier methods (diaphragm, condoms, spermicides).
oWomen who are practicing abstinence.
oWomen who have a partner who is sterile (eg, due to vasectomy).
Post-menopause is defined as:
oWomen who have had amenorrhea for ? 12 consecutive months (without another cause) and who have a documented serum follicle-stimulating hormone (FSH) level > 35 mIU/mL.
oWomen who have irregular menstrual periods and a documented serum FSH level > 35 mIU/mL.
oWomen who are taking hormone replacement therapy (HRT).
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 25
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

Exclusion Criteria

•Type 1 diabetes
•Urinary albumin excretion > 3500 mg/day
•Active malignancy
•Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following:
oHistory of active inflammatory bowel disease within the last six months;
oMajor gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
oGastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
oPancreatic injury or pancreatitis within the last six months;
oEvidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at inclusion visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt;
oEvidence of urinary obstruction of difficulty in voiding at screening
•History of severe hypersensitivity or contraindications to dapagliflozin
•Subject who, in the assessment of the investigator, may be at risk for dehydration or volume depletion that may affect the interpretation of efficacy or safety data
•Participation in any clinical investigation within 3 months prior to initial dosing.
•Donation or loss of 400 ml or more of blood within 8 weeks prior to initial dosing.
•History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening.
•History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
•Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
•Pregnancy or breastfeeding
•WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and up to 4 weeks after the last dose of study drug.