DapaBalci-Leap

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Winicker-Norimed Medizinische Forschung GmbH, Klinikum Nuernberg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Male Urogenital Diseases [C12]

Trial duration

13 Jul 2023 → 28 Jan 2026

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-516032-10-00

EudraCT number

2022-002721-99

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacokinetic, Efficacy, Pharmacodynamic

To show that treatment with balcinrenone preserves the beneficial dapagliflozin-driven increase in 24h renal glucose excretion

Secondary objectives 3

1. Topic 1 To demonstrate that the dapagliflozin-induced increase in urine solute concentration is not altered by balcinrenone
2. Topic 2 To demonstrate that treatment with dapagliflozin, with or without balcinrenone reduces free-water clearance within 48h, and further urine concentration is observed after 4 weeks, increases the contribution of glucose to osmotic-diuretic volume formation, decreases the contribution of sodium and urea to osmotic-diuretic volume formation, does not change the contribution of potassium to osmotic-diuretic volume formation within 48h, and that this effect persists after 4 weeks.
3. Topic 3 To demonstrate that patients treated with dapagliflozin alone or in combination with balcinrenone show increased plasma copeptin levels and show increased plasma glucagon and reduced plasma insulin levels within 48h and/or after 4 weeks.

Conditions and MedDRA coding

Stage 3 chronic kidney disease

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Age: Male and female patients over 50 years old Type of Participant and Disease Characteristics
2. Diagnosis of chronic kidney disease, with eGFR ≥30 and ≤60 mL/min/1.73m2
3. A) Germany: Serum/ plasma K+ levels ≥ 3.5 and < 5.0 mmol/L OR within normal laboratory ranges when these are provided, within 2 weeks prior to randomization B) France: Serum/ plasma K+ levels ≥ 3.5 and < 5.0 mmol/L within 2 weeks prior to randomization
4. Serum/plasma Na+ levels within normal reference values within 2 weeks prior to randomization
5. If participants have type 2 diabetes mellitus, treatment with metformin, sulphonylureas, 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, sulphonylureas, or DPP4 inhibitors or their combination as anti-diabetic therapy for the 12 weeks prior to randomization is required
6. No changes in background treatment for at least 3 weeks prior to randomization
7. Body mass index less than 40 kg/m2
8. Negative pregnancy test (urine or serum) for female subjects of childbearing potential and willingness to use a highly effective birth control (see Appendix 4) if of childbearing potential
9. Willingness to participate and ability to provide signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria 27

1. Diagnosis of type 1 diabetes mellitus
2. Uncontrolled type 2 diabetes mellitus with HbA1C > 10.5% in the most recent medical records
3. Participants with type 2 diabetes mellitus treated with insulin if insulin dosing (intermediate, long‐acting, premixed insulin, basal bolus insulin) was not stable in the 12 weeks prior to randomization as judged by the Investigator
4. Patients with systolic blood pressure levels <100 mmHg at the time of enrolment
5. Patients with congestive heart failure NYHA stage IV or hospitalized for decompensation of heart failure in the 3 months prior to screening
6. History of any life-threatening cardiac arrhythmias, or uncontrolled ventricular rate in participants with atrial fibrillation or atrial flutter
7. Acute coronary syndrome and/or percutaneous cardiac interventions within 3 months prior to screening
8. Unstable or rapidly progressing renal disease
9. Chronic cystitis and recurrent genital or urinary tract infections
10. Significant hepatic disease, including hepatitis and/or liver cirrhosis (Child-Pugh class A-C), or AST or ALT > 2 × ULN (upper limit of normal); or total bilirubin levels (TBL) > 2 × ULN; or serum albumin levels < 3.5 g/dL
11. Medical conditions associated with development of hyperkalemia (Addison's disease)
12. Stroke, transient ischemic attack, carotid surgery, or carotid angioplasty within 3 months prior to screening
13. A) Germany: Hemoglobin levels below 8.5 g/dL or over 15 g/dL OR over the normal laboratory ranges, when these are provided B) France: Hemoglobin levels below 8.5 g/dL or over 15 g/dL
14. A) Germany: Patients who have received an organ transplant at any time or bone marrow transplant in the previous 10 years B) France: Patients who have received an organ or bone marrow transplant
15. HIV infection
16. Active cancer, history of bladder cancer
17. Patients who have had major surgery in the 3 months prior to screening
18. Patients with muscular dystrophies
19. Patients who have severe comorbid conditions likely to compromise survival or study participation
20. Pregnant and breast-feeding women
21. Medical treatment with either a mineralocorticoid receptor antagonist (MRA) or a sodium-glucose co-transporter-2 inhibitor (SGLT2i) within 3 months prior to screening
22. Medical treatment with potassium binders
23. Medical treatment with strong or moderate CYP3A4 inducers or inhibitors
24. Prior serious hypersensitivity reaction to dapagliflozin (Forxiga®), balcinrenone or to any of their excipients
25. Treatment with cytotoxic therapy, immunosuppressive therapy or other immunotherapy within 6 months prior to screening
26. Unwillingness or other inability to cooperate
27. For patients undergoing MRI scans, presence of implanted devices (surgical clips, heart pacemakers or defibrillators, cochlear implants), iron-based tattoos, any other pieces of metal or devices that are not MR-safe anywhere in the body

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in 24h urine glucose excretion at day 3 and day 28

Secondary endpoints 21

1. Change from baseline in urine osmolality at day 3 and day 28
2. Change from baseline in urine glucose fraction at day 3 and day 28
3. Change from baseline in urine sodium fraction at day 3 and day 28; Change from baseline in urine urea fraction at day 3 and day 28
4. Change from baseline in urine potassium fraction after 48h and after 4 weeks
5. Change from baseline in muscle water content as measured at 7T MRI at day 28
6. Change from baseline in copeptin levels at day 3 and day 28
7. Change from baseline in plasma insulin/glucagon ratio at day 3 and day 28
8. Change from baseline in tissue Na+ content at day 28
9. Change from baseline in urine lithium/sodium excretion ratio at day 3 and day 28
10. Change from baseline in 24h urine indoxyl sulfate and indole 3 acetic acid excretion at day 28
11. Change from baseline in pH levels and phosphate metabolites levels at day 28 as quantified with 31P spectroscopy at 3T MRI
12. Change from baseline in 24h urine aldosterone levels at day 3 and day 28
13. Change from baseline in glucose-6-P Dehydrogenase activity at day 28
14. Change from baseline in GSH/GSSG ratio in the erythrocytes at day 28
15. Change from baseline in γ-glutamyl cysteine and glutathione synthase activity in the erythrocytes at day 28
16. Change from baseline in the cataplerotic component of the pentose phosphate pathway in erythrocytes at day 28
17. Change from baseline in the anaplerotic component of the pentose phosphate pathway in erythrocytes at day 28
18. Change from baseline in glutathione reductase, band 4.1a/4.1b protein, and creatine levels at day 28
19. Incidence and severity of treatment-emergent AEs
20. Changes in safety laboratory values from baseline to day 28
21. Changes in vital signs from baseline to day 28

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Winicker-Norimed Medizinische Forschung GmbH

Sponsor organisation

Winicker-Norimed Medizinische Forschung GmbH

Address

Deutschherrnstrasse 15-19, Kleinweidenmuehle Kleinweidenmuehle

City

Nuremberg

Postcode

90429

Country

Germany

Scientific contact point

Organisation

Winicker-Norimed Medizinische Forschung GmbH

Contact name

Eberhard Buchner

Public contact point

Organisation

Winicker-Norimed Medizinische Forschung GmbH

Contact name

Eberhard Buchner

Klinikum Nuernberg

Sponsor organisation

Klinikum Nuernberg

Address

Prof.-Ernst-Nathan-Strasse 1, St. Johannis St. Johannis

City

Nuremberg

Postcode

90419

Country

Germany

Scientific contact point

Organisation

Klinikum Nuernberg

Contact name

Adriana Marton

Public contact point

Organisation

Klinikum Nuernberg

Contact name

Adriana Marton

Sponsor responsibilities

Contact point sponsor

Winicker-Norimed Medizinische Forschung GmbH

Locations

2 EU/EEA countries · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications