A study to evaluate the efficacy and safety of gliclazide MR in patients with type 2 diabetes inadequately controlled with dapagliflozin with or without metformin

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut De Recherches Internationales Servier IRIS

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

15 Jul 2024 → 9 Dec 2025

Decision date (initial)

2024-06-27

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ADIR

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Efficacy

To demonstrate the superiority of the free combination of gliclazide MR and dapagliflozin (with or without metformin), in reducing HbA1c after 24 weeks of treatment, compared to placebo and dapagliflozin (with or without metformin) in participants with T2D not optimally controlled with dapagliflozin (with or without metformin).

Secondary objectives 2

1. To assess the effect of the free combination gliclazide MR and dapagliflozin compared to placebo and dapagliflozin, with or without metformin, over 24 weeks of treatment on different secondary endpoints in participants with T2D not optimally controlled with dapagliflozin (with or without metformin)
2. To assess the safety and tolerability of the free combination gliclazide MR and dapagliflozin compared with placebo and dapagliflozin, with or without metformin, over 24 weeks of treatment

Conditions and MedDRA coding

Type 2 Diabetes inadequately controlled with dapagliflozin with or without metformin

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Screening period: Participants with T2D diagnosed > 6 months, aged ≥ 18 years, body mass index (BMI) [25 – 40] kg/m2
2. Screening period: On stable regimen of diet and exercise and currently treated with: - Either metformin monotherapy at stable daily dose ≥ 1500 mg for at least 12 weeks prior to SCR1 visit and inadequately controlled with HbA1c [8.0%–11.5%] [64-102 mmol/mol] - Or dapagliflozin 10 mg or empagliflozin 10 or 25 mg, in monotherapy or in combination with metformin at daily dose ≥ 1500 mg, daily dose of both treatments must be stable for at least 12 weeks prior to SCR1 visit and inadequately controlled with HbA1c [7.5%-10.5%] [58- 91 mmol/mol]d
3. For enrolment in the randomised treatment period: HbA1c [7.0% – 10.5%], (53–91 mmol/mol; centralised value collected within the week prior to W000 visit)
4. For enrolment in the randomised treatment period: FPG ≤15 mmol/L (≤ 270 mg/dL), (centralised value collected within the week prior to W000 visit)
5. For enrolment in the randomised treatment period: For participant previously treated with metformin monotherapy: participant will be withdrawn if the fasting capillary BG > 15 mmol/L (270 mg/dL; average of 3 fasting SMBG) within the week before SCR3.

Exclusion criteria 7

1. With aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 times the upper limit of normal (ULN), bilirubin > 2 times the ULN, estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2, haemoglobin < 12 g/dL (males) or < 11g/dL (females).
2. With contraindication, known or suspected intolerance to gliclazide or dapagliflozin.
3. With uncontrolled hypertension (systolic blood pressure [SBP] > 180 mmHg and diastolic [DBP] > 100 mmHg).
4. With recent (in the previous 6 months) major cardiovascular events (myocardial infarction, cardiac surgery/ revascularisation, unstable angina, cerebrovascular accident including transient ischaemic attack (TIA), or stroke).
5. Treated within 8 weeks prior to the SCR1 visit with sulphonylureas, DPP-4 inhibitors, SGLT2i except dapagliflozin or empagliflozin, GLP-1 receptor agonists, α-glucosidase inhibitors, thiazolidinediones, meglitinides or insulin.
6. Treated within 8 weeks prior to the SCR1 visit with bile acid sequestrants (e.g. colesevelam), dopamine receptor agonists (e.g. bromocriptine), and amylin analogues (e.g. pramlintide).
7. Chronic (> 10 consecutive days) treatment with systemic corticosteroids within 8 weeks prior to the SCR1 visit (intra-basal, intra-articular, intra-ocular, inhaled or topical steroids are permitted).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline to week 24 in HbA1c.

Secondary endpoints 5

1. Change from baseline to week 24 in centralised fasting plasma glucose (FPG)
2. Proportion of participants at week 24 with: • HbA1c < 7.0% • HbA1c ≤ 6.5% • HbA1c < 7% without clinically important and/or severe hypoglycaemia
3. Proportion of participants requiring rescue therapy over 24 weeks
4. Adverse events, including hypoglycaemic events, genital infections, and urinary tract infections (UTIs)
5. Vital signs (SBP, DBP, HR), body weight and clinical laboratory measures (biochemistry and haematology)

Investigational products

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

Test 2

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut De Recherches Internationales Servier IRIS

Sponsor organisation

Institut De Recherches Internationales Servier IRIS

Address

22 Route 128

City

Gif Sur Yvette

Postcode

91190

Country

France

Scientific contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Public contact point

Organisation

Institut De Recherches Internationales Servier IRIS

Contact name

Clinical Studies Department

Third parties 3

Locations

5 EU/EEA countries · 41 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 71 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