2-week Dapagliflozin therapy effect on sodium elimination in patients with type 2 diabetes mellitus and renal disease

Phase 1

• Conditions: Type 2 diabetes mellitus (T2DM) with impaired renal function; MedDRA version: 23.0Level: PTClassification code 10012607Term: Diabetes mellitus inadequate controlSystem Organ Class: 10027433 - Metabolism and nutrition disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2020-001247-12-NL
• Lead Sponsor: niversity Medical Center Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-09-30
• Last Update Posted: 8 October 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 17

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%
(<97 mmol/mol); and eGFR (CKD-EPI) between =25 and =50 mL/min/1.73m2
4. Patient specific optimal antihypertensive dose of an ACEi or ARB (as per
Investigator’s judgement) for at least 6 weeks prior to Visit 4 (Day 1).
5. A stable insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) for the last 12 weeks prior to Visit 4 (Day 1) as judged by the Investigator.
Metformin, sulphonylurea, DPP4 inhibitors or any combinations of these agents with
or without insulin would be accepted but is not mandatory. If used, stable dose of metformin, sulphonylurea, or DPP4 inhibitors or their combination as anti-diabetic
therapy for the last 12 weeks prior to start of treatment with dapagliflozin is required.
6. Suitable veins for cannulation or repeated venepuncture
7. Female patients must be 1 year post-menopausal, surgically sterile, or using an
acceptable method of contraception (an acceptable method of contraception is
defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of study drug to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.

Patients must fulfil the following criteria in order to continue participation in the
study:
8. Patient specific optimal antihypertensive dose of an ACEi or ARB (as per
Investigator’s judgement) for at least 6 weeks prior to Visit 4 (Day 1).
9. A stable insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) for the last 12 weeks prior to Visit 4 (Day 1) as judged by the Investigator. Metformin, sulphonylurea, DPP4 inhibitors or any combinations of these agents with or without insulin would be accepted but is not mandatory. If used, stable dose of
metformin, sulphonylurea, or DPP4 inhibitors or their combination as anti-diabetic
therapy for the last 12 weeks prior to start of treatment with dapagliflozin is required.
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 2
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

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 <50 bpm or >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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified