SGLT2 inhibition in addition to lifestyle intervention and risk for complications in subtypes of patients with prediabetes - a randomized, placebo controlled, multi-center trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

26 Oct 2023 → ongoing

Decision date (initial)

2024-10-10

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-512179-11-00

EudraCT number

2021-005721-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Therapy

To test if hyperglycemia in patients with prediabetes can be normalized by a
treatment with the sodium-glucose co- transporter-2
(SGLT2) inhibitor dapagliflozin (10mg/day) and lifestyle
counselling compared to placebo and lifestyle counselling
for six months

Conditions and MedDRA coding

Patients with prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT])

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Male, female or intersexualpatients aged between 35 and 75 years (including)
2. Prediabetes (defined by one of the following: FG ≥ 100 mg/dL or 2h OGTT glucose ≥ 140mg/dL)
3. BMI ≥20 kg/m2
4. TSH within normal range
5. Ability to understand and follow study-related instructions
6. Negative pregnancy test for premenopausal women (blood)
7. Patients who are receiving thyroid replacement therapy must be on a stable treatmentregimen for at least 3 months prior to the screening visit (V-1)
8. Patients who are receiving antihypertensive medication such as mineralocorticoidreceptor antagonists must be on a stable treatment regimen for at least 6 weeks prior tothe screening visit (V-1)
9. Patients who are treated antihypertensive medication such as ACE inhibitors and AT1receptor antagonists, thiazides as well as loop diuretics must be on stable treatment forat least 2 weeks
10. Understand and voluntarily sign an informed consent document prior to any studyrelated assessments/procedures.
11. Patients will not be included in the study if, in the opinion of the investigator,participation will lead to an unacceptable risk to the subjects’ safety or well-being

Exclusion criteria 30

1. Manifest diabetes mellitus
2. eGFR (as calculated by the CKD-EPI equation) < 60 ml/min/1.73 m2
3. all glucose altering medications (including current therapy with dapagliflozin or empagliflozinor any other SGLT2-Inhibitor)
4. Symptomatic chronic congestive heart disease
5. New diuretic or antihypertensive medication or dosing changes within the last 2 weeks, foraldosterone antagonists within the last 6 weeks
6. known or suspected orthostatic proteinuria
7. any acute severe or chronic severe illness, including the following: malignant disease ongoingor < 5 years ago, unstable cardiovascular disease or procedure within 3 months prior toenrolment or expected to require coronary revascularisation procedure
8. history of or current therapy for congestive heart failure (NYHA III and IV), pacemaker oraortic stenosis > II°
9. acute pancreatic disease (i.e. elevated lipase 3x ULN)
10. rapidly progressing renal disease or anuria
11. known HIV infection or positive HIV test at screening
12. history of or planned organ transplantation
13. history or presence of inflammatory bowel disease or other severe gastrointestinal diseases,particularly those which may impact gastric emptying, such as gastroparesis or pyloricstenosis
14. relevant hepatic disease, including, but not limited to, acute hepatitis, chronic activehepatitis, or severe hepatic insufficiency, including patients with alanine aminotransferaseand/or aspartate aminotransferase > 3 x upper limit of normal and/or total bilirubin (TB) > 2mg/dL (> 34.2 μmol/L) (patients with TB > 2 mg/dL [> 34.2 μmol/L] and documented Gilbert’ssyndrome will be allowed to participate)
15. treatment with glucocorticoids
16. antibiotic treatment within the last 4 weeks
17. History of ketoacidosis
18. history of repeated urogenital infection
19. hemoglobinopathies, haemolytic anaemia, or chronic anaemia (haemoglobin concentration <12.0 g/dL)
20. presence of psychiatric disorder or new intake of antidepressant or antipsychotic agents(start within last 3 months)
21. Positive Screening for a severe depression (BDI ≥29)
22. history of hypersensitivity to the study drug or its ingredients
23. more than 5% weight loss in the last 3 months
24. Pregnant or breastfeeding women
25. Subject (male, female or intersexual) is not willing to use highly effective contraceptivemethods during treatment and for 14 days (male or female) after the end of treatment(highly effective methods are defined as: combined hormonal contraception associated withinhibition of ovulation, progestogen-only hormonal contraception associated with inhibitionof ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubalocclusion, vasectomized partner, sexual abstinence)
26. Current participation in other interventional clinical trials or treatment with other IMPswithin five times the half-life of the drug
27. Previous therapy with dapagliflozin or other drugs that can potentially lead to overlappingtoxicities within five times the half-life of the drug
28. Patients who do not want to be informed about accidental findings
29. Any other clinical condition that would jeopardize subjects’ safety or well-being whileparticipating in this clinical trial
30. Patients will not be included in the study if, in the opinion of the investigator, participationleads to an unacceptable risk to their safety and well-being

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Frequency of remission of hyperglycemia in patients in highand low risk for CKD with prediabetes at EoT in thedapagliflozin versus the placebo group defined as a fastingglucose <100 mg/dl and 2 h glucose <140 mg/dl (Objective1)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tuebingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Projectmanager

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Projectmanager

Locations

1 EU/EEA country · 9 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 9 files

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

Application history

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