DAPASALT: An Open Label, Phase IV, Mechanistic, Three-Arm Study to Evaluate the Natriuretic Effect of 2-Week Dapagliflozin treatment in Type 2 Diabetes Mellitus Patients with Either Preserved or Impaired Renal Function and Non-Diabetics with Impaired Renal Functio
- Conditions
- diabetes mellitusrenal failure1001842410038430
- Registration Number
- NL-OMON49588
- Lead Sponsor
- Astra Zeneca
- Brief Summary
Trial is onging in other countries
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 45
Based on Protocol amendment 5.0, 1. In the diabetic arms - a diagnosis of T2DM
with glycosylated haemoglobin (HbA1c) >=6.5% (>=48 mmol/mol)
and <10% (<86 mmol/mol); and eGFR (CKD-EPI) between >=25 and <=50 mL/min/1.73m2
or between >90 and <=130 mL/min/1.73m2 for patients aged 59 or younger, between
>85 and <=130 mL/min/1.73m2 for patients aged 60 to 69, and between >75 and <=130
mL/min/1.73m2 for patients aged 70 or older at the Screening Visit (Visit 1).,
2. In the non-diabetic arms, HbA1c <6.5% (<48 mmol/mol) and an eGFR (CKD-EPI)
between >=25 and <=50 mL/min/1.73m2 at the Screening Visit (Visit 1)., 3. Patient
specific optimal antihypertensive dose of an angiotensin receptor blocker (ARB)
(as per Investigator*s judgement) for at least 6 weeks prior to Visit 4 (Day
1)., 4. In the diabetic arm (Group 2) an appropriate stable dose of metformin,
or sulphonylurea, or metformin+sulphonylurea as anti-diabetic therapy for the
last 12 weeks prior to (Visit 4, Day 1)., 5. In the diabetic arm with impaired
renal function (Group 1) 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 or sulphonylurea, or
metformin+sulphonylurea together with insulin would be accepted, but is not
mandatory. If used, stable dose of metformin or sulphonylurea, or
metformin+sulphonylurea as anti-diabetic therapy for the last 12 weeks prior to
Visit 4 (Day 1) is required., 6. Stable urinary sodium excretion on 2
successive 24-hr urinary sodium excretion measurements (<20% difference between
Days *3 and *2)., For an extensive description of the inclusion criteria, see
Protocol paragraph 4.1
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, Day *28 until day -8).
2. Involvement in the planning and conduct of the study (applies to both
AstraZeneca 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; 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. Diagnosis of polycystic kidney disease.
17. History of or current lupus nephritis.
18. Urinary albumin excretion >1000 mg/g per day at the Screening Visit based
on spot urine sample (quantitative assessment)., for further details, see
Protocol v5.0 paragraph 4.2.1
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Average change in 24-hr sodium excretion from average baseline to average<br /><br>values at Day 2 to 4 within each study group. </p><br>
- Secondary Outcome Measures
Name Time Method