Type 2 diabetes mellitus (T2DM) with impaired renal function MedDRA version: 23.0 Level: PT Classification code 10012607 Term: Diabetes mellitus inadequate control System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Trade Name: Forxiga
Pharmaceutical Form: Tablet
Sponsors
University Medical Center Groningen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients will be entered into this study only if they meet all of the following criteria: 1. Provision of signed and dated, written informed consent prior to any study-specific procedures. 2. Female and/or male aged between 18 years and = 80 years. 3. A diagnosis of T2DM with HbA1c =6.5% (=48 mmol/mol) and =11% (=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 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 6 months 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. Pacemaker or other implanted electronic devices. 5. Pregnancy. 6. Breastfeeding. General health-related: 7. 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. 8. Diagnosis of T1DM. 9. Hyperthyroidism or autonomic thyroid adenomas. 10. 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. - Pulse 100 bpm 11. 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. 12. Patients with severe hepatic impairment (Child-Pugh C). 13. 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: 14. Symptoms/complaints suggestive of established neurogenic bladder and/or incomplete bladder emptying. 15. History of bladder cancer. 16. Non-diabetic kidney disease. 17. UACR >2200 mg/g at the Screening Visit based on spot urine sample (quantitative assessment). Concomitant Medication and/or study treatment-related: 18. Current/chronic use of the following medication: glucagon-like peptide receptor agonists or thiazolidinediones, oral glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors. 19. Receiving immunosuppressive or other immunotherapy for primary or secondary renal disease within 6 months prior to Screening Visit (Visit 1). 20. Current treatment or treatment within the last 2 weeks prior to Screening Visit (Visit 1) with mineralocorticoid antagonists (loop or thiazide diuretics are allowed as long as they are used in stable do
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate change in 24-hr sodium excretion during dapagliflozin treatment between Baseline (average of Days -3 to -1) and average of Days 2 to 4 within each study group in patients with type 2 diabetes mellitus (T2DM) with impaired renal function.;Secondary Objective: The secondary objectives to be evaluated: • change in 24-hr sodium excretion during dapagliflozin treatment from Baseline to end of treatment, and during follow-up • change in 24-hr glucose excretion • change in mean 24-hr systolic blood pressure • change in plasma volume • change in extracellular volume • pharmacokinetics of dapagliflozin • the change in 24-hr urine albumin: creatinine ratio (UACR) The safety objectives to be evaluated: • safety and tolerability of dapagliflozin in patients with type 2 diabetes and renal impairment;Primary end point(s): Average change in 24-hr sodium excretion from average Baseline to average values at Day 2 to 4 within each study group.;Timepoint(s) of evaluation of this end point: Day 2 to 4 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 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 Days 4 and 14. • Average change in mean 24-hr UACR from average Baseline to Day 4; and from average Baseline values to average end of treatment values (Day 12 to 14). Safety Endpoints: • AEs starting from first dose throughout the study including the follow-up period. • SAEs starting from Visit 1 throughout the study including the follow-up period. • Laboratory variables. • Vital signs. • Physical examination.;Timepoint(s) of evaluation of this end point: From end of treatment (Day 14) to end of follow-up (Day 18) | — |
Countries
Canada, Netherlands, United States
Contacts
Public ContactDr. Hiddo Heerspink
University Medical Center Groningen
Outcome results
None listed