adult-onset diabetes non-insulin-dependant diabetes
Conditions
Interventions
The study consists of a 2-week, open label, Treatment Period. Patients will be
provided with one bottle of dapagliflozin tablets on Day 1 (Visit 4) to last
for the 14±1 days of the Treatment Period.
Sponsors
Universitair Medisch Centrum Groningen
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: The study population will consist of patients withT2DM with an eGFR (CKD-EPI) between >=25 and =6.5% (>=48 mmol/mol) and =25 and
Exclusion criteria
Exclusion criteria: 4.1.3 Exclusion Criteria at Screening Visit (Visit 1) Patients will not be entered into this study if they meet any of the following criteria: Study-related: 1. Previous enrolment in the present study or participation in another clinical study with an investigational product during the last 30 days prior to Screening Visit (Visit 1). 2. Involvement in the planning and conduct of the study (applies to both UMCG staff and staff at third party vendor or at the investigational sites). 3. Hypersensitivity to dapagliflozin, indocyanine green, sodium iodide, or iodine, or patients who have poorly tolerated indocyanine green in the past. 4. Pregnancy or breastfeeding. General health-related: 5. Known clinically significant disease or disorder; or clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, and urinalysis; or unstable or rapidly progressing renal disease; other dietary restrictions that would make it difficult for the subject to follow the protocol required diet plan or any other condition or minor medical complaint, which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study, or influence the results, or the patient*s ability to participate in the study and comply with study procedures, restrictions and requirements. 6. Diagnosis of T1DM. 7. Hyperthyroidism or autonomic thyroid adenomas. 8. Abnormal vital signs, after 10 minutes supine rest, defined as any of the following (Visit 1): - Systolic blood pressure above 180 mmHg. - Diastolic blood pressure above 110 mmHg. 9. Any of the following cardiovascular/vascular diseases within 3 months prior to signing the consent at Visit 1, as assessed by the Investigator: myocardial infarction, cardiac surgery or revascularization (coronary artery bypass graft [CABG]/ percutaneous transluminal coronary angioplasty [PTCA]), unstable angina, unstable heart failure, heart failure New York Heart Association Class IV, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia. 10. Patients with severe hepatic impairment (Child-Pugh C). 11. Ongoing weight-loss diet (hypocaloric diet) or use of weight-loss agents, unless the diet or treatment has been stopped at least 3 months before Screening Visit, ensuring patients having a stable body weight with no verified body weight variability of >3 kg during the 3 months before Screening Visit. Renal failure-related: 12. Symptoms/complaints suggestive of established neurogenic bladder and/or incomplete bladder emptying. 13. History of bladder cancer. 14. Non-diabetic kidney disease. 15. UACR >2200 mg/g per day at the Screening Visit based on spot urine sample (quantitative assessment). Concomitant Medication and/or study treatment-related: 16. Current/chronic use of the following medication: glucagon-like peptide receptor agonists or thiazolidinediones, oral glucocorticoids (if dose is stable for at least 4 weeks this is allowed), non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (as per Investigator's judgement). 17. Receiving immunosuppressive or other immunotherapy for primary or secondary re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The change in 24-hr sodium excretion during dapagliflozin treatment between Baseline (average of Days *3 to *1) and average of Days 2 to 4 in patients with type 2 diabetes mellitus (T2DM) with impaired renal function. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoints to be evaluated during or following dapagliflozin treatment within each study group are: • Average change in 24-hr sodium excretion from average Baseline values to average end of treatment values (Day 12 to 14); and from average end of treatment values (Day 12 to 14) to average values during follow-up (Day 15 to 17). • Average change in 24-hr glucose excretion from average Baseline values to average values at Day 2 to 4; from average Baseline values to average end of treatment values (Day 12 to 14); and from average end of treatment values (Day 12 to 14) to average values during follow-up (Day 15 to 17). • Change in mean 24-hr systolic blood pressure from Baseline to Day 4; from Baseline to end of treatment (Day 13); and from end of treatment (Day 13) to end of follow-up (Day 18). • Change in plasma volume from Baseline to Day 4; from Baseline to end of treatment (Day 14); and from end of treatment (Day 14) to end of follow-up (Day 18). • Change in extracellular volume from Baseline to Day 4; from Baseline to end of treatment (Day 14); and from end of treatment (Day 14) to end of follow-up (Day 18). • Dapagliflozin pharmacokinetics on Day 4 and Day 14. • Average change in mean 24-hr UACR from average Baseline to Day 4; from average Baseline values to average end of treatment values (Day 12 to 14). The exploratory endpoints to be evaluated during or following dapagliflozin treatment within each study group are: •Change in day (0600 - 2200):night (2200 - 0600) ratio of systolic blood pressure from Baseline to Day 4; from Baseline to end of treatment (Day 13); and from end of treatment (Day 13) to end of follow-up (Day 18). •Change in the following from Baseline to Day 4; from Baseline to end of treatment (Day 14); and from end of treatment (Day 14) to end of follow-up (Day 18). - Hormones of the RAAS (plasma/urine renin*, urine aldosterone*, plasma AngII, uAngiotensinogen*). - NT-proBNP and BNP. - Urinary aden | — |
Countries
Netherlands
Outcome results
None listed