E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with type 2 diabetes and albuminuria between 100 and 3500 mg/g. |
Patineten met type 2 diabetes en albuminurie tussen 100 en 3500 mg/g |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Suikerziekte |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the change from baseline in 24-hr albuminuria with dapagliflozin for six weeks relative to placebo treatment in patients with type 2 diabetes and albuminuria between 100 and 3500 mg/day on stable ACEi or ARB treatment. |
Bepalen van de verandering in 24-uurs albuminurie excretie met dapagliflozine behandeling voor een periode van 6 weken ten opzichte van placebo behandeling in patienten met type 2 diabetes en albuminurie tussen 100 en 3500 mg/g die op een stabiele dosis staan van een ACE-remmer of AII-antagonist. |
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E.2.2 | Secondary objectives of the trial |
To assess: • the within-patient variability in HbA1c, 24-hr blood pressure, body weight, and albuminuria response to dapagliflozin. • the between-patient variability in HbA1c, 24-hr blood pressure, body weight, and albuminuria response to dapagliflozin. • the variability in HbA1c, blood pressure, body weight, and albuminuria in response to dapagliflozin during the first and second treatment period. |
Het bepalen van: - De variabiliteit binnen een patient in de response van Hba1c, 24-uurs bloeddruk, lichaamsgewicht en albuminurie tijdens behandeling van dapagliflozine - the variabiliteit tussen patienten in Hba1c, 24-uurs bloeddruk, lichaamsgewicht en albuminurie tijdens behandeling van dapagliflozine -de variabiliteit in hba1c, bloeddruk, lichaamsgewicht en albuminurie tussen de eerste en tweede behandelperiode met dapagliflozine
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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): o WOCBP 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. o WOCBP 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. o Women 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: o Women 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). o Women who are practicing abstinence. o Women who have a partner who is sterile (eg, due to vasectomy). Post-menopause is defined as: o Women 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. o Women who have irregular menstrual periods and a documented serum FSH level > 35 mIU/mL. o Women who are taking hormone replacement therapy (HRT). |
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E.4 | Principal 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: o History of active inflammatory bowel disease within the last six months; o Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; o Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months; o Pancreatic injury or pancreatitis within the last six months; o Evidence 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; o Evidence 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in 24-hr albuminuria |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change in 24-hr albuminuria will be calculated from day 0 to day 42 (week 6) |
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E.5.2 | Secondary end point(s) |
HbA1c, 24-hr blood pressure, body weight |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change in HbA1c, 24-hr blood pressure, body weight will be calculated from day 0 to day 42 (week 6) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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End of the trial is defined as the last visit of the last subject |
Einde van de studie is gedefinieerd als de laatste visite van de laatste deelnemer |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |