An Open Label, Phase IV, Mechanistic, Study to Evaluate the Natriuretic Effect of 2-Week Dapagliflozin treatment in Type 2 Diabetes Mellitus Patients with Impaired Renal Functio

Phase 4

Recruiting

• Conditions: adult-onset diabetes; non-insulin-dependant diabetes; 10012653

• Registration Number: NL-OMON52111
• Lead Sponsor: niversitair Medisch Centrum Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 6

Inclusion Criteria

The study population will consist of patients withT2DM with an eGFR (CKD-EPI)
between >=25 and <=50 mL/min/1.73m2 at the Screening Visit

Inclusion Criteria at Screening Visit (Visit 1)
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 <=12% (<97
mmol/mol), if using insulin or sulfonylurea (for those patients not taking
insulin or sulfonylurea there is no lower limit for HbA1c). T2DM patients on
insulin or sulfonylurea who do not meet the HbA1c requirement can have their
medication readjusted per Investigator's judgement and rescreened after 3
months on new dose; 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, GLP1 receptor agonists
or any combinations of these agents with or without insulin would be accepted
but is not mandatory. If used, stable dose of metformin, sulphonylurea, DPP4
inhibitors, GLP1 receptor agonists or their combination as anti-diabetic
therapy for the last 12 weeks prior to start of treatment with dapagliflozin is
required (as per Investigator's judgement).
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.

4.1.2 Inclusion Criteria at End of Run-in Period (Visit 3)
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) (as per
Investigator's judgement).
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, GLP 1 receptor
agonists 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 GLP 1 agonists or their combination as
anti-diabetic therapy for the last 12 weeks prior to start of treatment with
dapagliflozin is required (as per Investigator's judgement).

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The change in 24-hr sodium excretion during dapagliflozin treatment between<br /><br>Baseline (average of Days *3 to *1) and average of Days 2 to 4 in patients with<br /><br>type 2 diabetes mellitus (T2DM) with impaired renal function.</p><br>