Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ended
Participants planned
10
Countries
1
Sites
1
Albuminuria
To determine the feasibility and advantages of remote clinical trial conduct with multiple medications in patients with type 2 diabetes and elevated albuminuria.
Key facts
- Sponsor
- Universitair Medisch Centrum Groningen
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Hormonal diseases [C19], Diseases [C] - Nutritional and Metabolic Diseases [C18], Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]
- Trial duration
- 29 Jul 2024 → 24 Sep 2025
- Decision date (initial)
- 2024-04-25
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- Boehringer Ingelheim
External identifiers
- EU CT number
- 2023-508585-15-00
- WHO UTN
- U1111-1298-4774
- ClinicalTrials.gov
- NCT06094920
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Others
To determine the feasibility and advantages of remote clinical trial conduct with multiple medications in patients with type 2 diabetes and elevated albuminuria.
Secondary objectives 3
- To determine the individual response to the SGLT2 inhibitor empagliflozin in urine albumin-creatinine ratio (UACR).
- To determine the individual response to the SGLT2 inhibitor empagliflozin in systolic blood pressure, body weight, estimated glomerular filtration rate (eGFR), and fasting plasma glucose.
- To assess if suboptimal treatment responses to empagliflozin can be overcome by the addition or substitution with finerenone.
Conditions and MedDRA coding
Albuminuria
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.1 | LLT | 10045242 | Type II diabetes mellitus | 10027433 |
| 20.0 | PT | 10001580 | Albuminuria | 100000004857 |
| 21.1 | LLT | 10045250 | Type II diabetes mellitus with renal manifestations | 10038359 |
Study design 4 periods
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Participant identification and screening visit Potential participants will be identified by their treating physician by assessing eligibility in the electronic patient file. These potential participants will then be approached to gauge their interest and willingness to join the study. Subsequently, members of the study team will conduct telephone calls to provide further information, answer queries, and schedule screening visit appointments. Patients will receive an invitation letter containing a comprehensive explanation of the study, its pros and cons, and contact details for the research team members involved. The letter will also include contact information for an independent physician who can address any questions about the research before, during, and after the study. Patients will be given a two-week period to consider participation before being asked to provide written informed consent to participate in the study.
After informed consent, patient eligibility is determined at the screening visit. Patients will be instructed to collect two consecutive first-morning void urines to determine the level of albuminuria. A physical examination will be performed, vital signs will be checked, blood samples will be taken for clinical chemistry assessments and patient’s medical history, demographics, concomitant medications, and education level will be recorded for assessment. Furthermore, the team will evaluate the participants’ ability to use digital technologies, conduct measurements, and collect urine and blood samples at home. If laboratory measurements have been conducted for clinical care within the month leading up to the screening visit, the obtained values can be utilized for the purpose of study screening. Women with child-bearing potential will perform a pregnancy test. Patients who did not fulfil eligibility criteria can be re-screened for a maximum of three times and only parameters that fell out of range have to be re-tested.
Any disqualifying albuminuria, eGFR, hemoglobin A1c (HbA1c), or blood pressure level may be repeated two more times, at the discretion of the investigator and where there is a clinical reason to do so. The repeat value should be assessed prior to the patient recorded as having screen failed. If the repeat value falls within the ranges defined by the protocol and the patient meets all other inclusion criteria, the patient is eligible for the study.
|
Not Applicable | None | ||
| 2 | Run-in (-1 to 0 weeks) All participants will proceed to a run-in period. The purpose of the run-in period is to adequately determine baseline clinical characteristics. At the beginning of the run-in period, participants will come to the study site for a baseline visit. During this visit, patients will have a brief physical examination, vital signs check and will provide blood and urine samples. Participants will receive study drugs for the first 3-week treatment period, as well as devices to collect and export urine and capillary blood samples, and ambulant devices to measure their blood pressure and body weight. They will also receive thorough instructions on using these devices and drug administration. To make participants comfortable with the technique of blood collection, they will first collect a capillary blood sample at the study site during the baseline visit, supervised by a trained laboratory technician. A venous blood sample will also be obtained to enable comparison of clinical chemistry assessments between capillary and venous blood samples.
|
Not Applicable | None | ||
| 3 | Treatment period 1 (0 to 3 weeks) After enrolment and run-in, eligible participants will be assigned to a 3-week treatment period with the SGLT2 inhibitor empagliflozin 10 mg/day, in accordance with guidelines.
|
Not Applicable | None | ||
| 4 | Treatment period 2 (3 to 7 weeks) After 2 weeks of empagliflozin treatment, albuminuria levels will be assessed to determine the individual albuminuria response. Depending on the response (decrease or increase), participants will be allocated to one of three treatment regimens following the 3-week empagliflozin treatment period.
|
Not Applicable | None | Treatment regimen A: Albuminuria reduction >30% and the remaining albuminuria level is <30 mg/g: continue empagliflozin for an additional four weeks. Treatment regimen B: Albuminuria reduction >30% or >0 and ≤30%, and the remaining albuminuria level is >30 mg/g: continue empagliflozin for an additional four weeks and intensify treatment by adding finerenone for four weeks. Treatment regimen C: No albuminuria reduction or increase: discontinue empagliflozin and switch to finerenone for four weeks. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 7
- Age ≥18 years
- Diagnosis of type 2 diabetes
- UACR >4.5 mg/mmol (>40 mg/g) and ≤300 mg/mmol (≤2655 mg/g)
- eGFR ≥25 mL/min/1.73m^2
- On a stable dose of an ACE inhibitor/ARB if tolerated
- Willing to sign informed consent
- Proficiency in the Dutch language
Exclusion criteria 22
- Diagnosis of type 1 diabetes
- Already being treated with any SGLT2 inhibitor or MRA
- Unable to monitor blood pressure or body weight or handle digital technologies
- Heart failure NYHA Class II to IV requiring MRA treatment
- Acute coronary syndrome event within 6 months
- Serum potassium >5 mmol/L after repeated measurement
- Evidence of severe hepatic impairment determined by any of one: ALT or AST values exceeding 3 times ULN, a history of hepatic encephalopathy, a history of oesophageal varices, or a history of portocaval shunt
- Active pregnancy or breastfeeding
- History of kidney or liver transplant
- Unstable or rapidly progressing renal disease
- Active malignancy
- Suggestive evidence of adrenal insufficiency
- History of severe hypersensitivity or contraindications to any SGLT2 inhibitor or MRA
- Uncontrolled arterial hypertension (mean sitting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg)
- Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following: History of active inflammatory bowel disease within the last 6 months; Major gastrointestinal tract surgery as decided by the physician; Pancreatitis within the last 6 months; Gastrointestinal ulcers and/or bleeding within the last 6 months; Evidence of urinary obstruction or difficulty in voiding at screening
- Participation in any clinical trial within 3 months prior to initial dosing
- Donation or loss of ≥400 mL of blood within 8 weeks prior to initial dosing
- Confirmed lactose intolerance demonstrated with a lactose intolerance test
- History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening or according to investigator’s assessment
- History of noncompliance to medical regimens or unwillingness to comply with the study protocol
- Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study
- Women of childbearing potential (WOCBP): WOCBP who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of the study drug in such a manner the risk of pregnancy is minimized; WOCBP must have a negative serum or urine pregnancy test result (minimum sensitivity 25 IU/L or equivalent of HCG) at screening. WOCBP comprises women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or who are not post-menopausal. The following women are NOT considered as WOCBP: Women using the following methods to prevent pregnancy: oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as intrauterine devices or barrier methods (diaphragm, condoms, spermicides); Women who are practicing abstinence; Women who have a partner who is sterile (e.g. due to vasectomy). Post-menopause is defined as: Women who have had amenorrhea for >12 consecutive months (without another cause) and who have a documented serum follicle-stimulating hormone (FSH) level >35 mIU/mL; Women who have irregular menstrual periods and a documented serum FSH level >35 mIU/mL; Women who are taking hormone replacement therapy (HRT)
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 4
- Questionnaire results: participants’ perspectives toward the feasibility of participation in a trial at home with digital technologies
- Number and percentage of urine collections not received at the laboratory or unable to be analyzed
- Number and percentage of missed blood pressure or body weight measurements
- Treatment adherence: pill count and medication concentration in urine samples
Secondary endpoints 3
- Change from baseline in UACR from start to end of treatment with empagliflozin
- Change from baseline in systolic blood pressure, body weight, eGFR, and fasting plasma glucose from start to end of treatment with empagliflozin
- (Additive) treatment effects on UACR, systolic blood pressure, body weight, eGFR, and fasting plasma glucose from start to end of treatment after the addition or substitution with finerenone
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 3
Jardiance 10 mg film-coated tablets
PRD1594848 · Product
- Active substance
- Empagliflozin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 7 Week(s)
- Authorisation status
- Authorised
- ATC code
- A10BK03 — -
- Marketing authorisation
- EU/1/14/930/010
- MA holder
- BOEHRINGER INGELHEIM INTERNATIONAL GMBH
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabelling and repacking
Kerendia 10 mg film coated tablets
PRD9506151 · Product
- Active substance
- Finerenone
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 10 mg milligram(s)
- Max total dose
- 10 mg milligram(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- C03DA05 — -
- Marketing authorisation
- EU/1/21/1616/001
- MA holder
- BAYER AG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabelling and repacking
Kerendia 20 mg film-coated tablets
PRD9506430 · Product
- Active substance
- Finerenone
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL USE
- Max daily dose
- 20 mg milligram(s)
- Max total dose
- 20 mg milligram(s)
- Max treatment duration
- 4 Week(s)
- Authorisation status
- Authorised
- ATC code
- C03DA05 — -
- Marketing authorisation
- EU/1/21/1616/006
- MA holder
- BAYER AG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- Relabelling and repacking
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitair Medisch Centrum Groningen
- Sponsor organisation
- Universitair Medisch Centrum Groningen
- Address
- Hanzeplein 1
- City
- Groningen
- Postcode
- 9713 GZ
- Country
- Netherlands
Scientific contact point
- Organisation
- Universitair Medisch Centrum Groningen
- Contact name
- Hiddo Lambers Heerspink
Public contact point
- Organisation
- Universitair Medisch Centrum Groningen
- Contact name
- Jelle Beernink
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ended | 10 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Ziekenhuisgroep Twente Stichting
Internal Medicine / Nephrology, Zilvermeeuw 1, 7609 PP, Almelo
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Netherlands | 2024-07-29 | 2025-09-24 | 2024-07-29 | 2025-06-05 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-02-06 | Netherlands | Acceptable 2024-04-25
|
2024-04-25 |