Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO)TM

Inclusion criteria

• Patients aged 10 to 17 years (inclusive) at the time of randomisation (Visit 2)
• Male and female patients
• Women of childbearing potential (WOCBP) must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient's legal representative information sheet.
• Signed and dated written informed consent provided by the patient's parent(s) (or legal guardian) and patient's assent in accordance with ICH-GCP and local legislation prior to admission to the trial (informed assent will be sought according to the patient's age, level of maturity, competence and capacity)
• Documented diagnosis of T2DM at Visit 1A:

• DINAMO TM: Documented diagnosis of T2DM for at least 8 weeks at Visit 1A
• DINAMO TM Mono: Confirmation of T2DM at Visit 1A
• Insufficient glycaemic control as measured by the central laboratory at Visit 1A:

• DINAMO TM: HbA1c ≥ 6.5% and ≤ 10.5%
• DINAMO TM Mono: HbA1c ≥ 6.5% and ≤ 9.0%
• DINAMO TM: Patients treated with

• diet and exercise plus metformin at a stable dose for 8 weeks prior to Visit 2 or not tolerating metformin (defined as patients who were on metformin treatment for at least 1 week and had to discontinue metformin due to metformin-related side effects as assessed by the investigator) AND/OR
• diet and exercise plus stable basal or MDI insulin therapy,, defined as a weekly average variation of the basal insulin dose ≤ 0.1 IU/kg over 8 weeks prior to Visit 2. - DINAMOTM Mono: Drug-naïve patients or patients not on active treatment (including discontinuation of metformin due to intolerance [or previous discontinuation for other reasons] and/or discontinuation of insulin [insulin use must be 8 weeks or less] at investigator's discretion) prior to or at Visit 1A)
• BMI ≥ 85th percentile for age and sex according to WHO references at Visit 1B
• Non-fasting serum C-peptide levels ≥ 0.6 ng/ml as measured by the central laboratory at Visit 1A
• Compliance with trial medication intake must be between 75% and 125% during the open-label placebo run-in period
• Further inclusion criteria apply

Exclusion criteria

• Any history of acute metabolic decompensation such as diabetic ketoacidosis within 8 weeks prior to Visit 1A and up to randomisation (mild to moderate polyuria at the time of randomisation is acceptable)
• Diagnosis of monogenic diabetes (e.g. MODY)
• History of pancreatitis
• Diagnosis of metabolic bone disease
• Gastrointestinal disorders that might interfere with study drug absorption according to investigator assessment
• Secondary obesity as part of a syndrome (e.g. Prader-Willi syndrome)
• Any antidiabetic medication (with the exception of metformin and/or insulin background therapy) within 8 weeks prior to Visit 1A and until Visit 2
• Treatment with weight reduction medications (including anti-obesity drugs) within 3 months prior to Visit 1A and until Visit 2
• History of weight-loss surgery or current aggressive diet regimen (according to investigator assessment) at Visit 1A and until Visit 2
• Treatment with systemic corticosteroids for > 1 week within 4 weeks prior to Visit 1A and up to Visit 2 Inhaled or topical use of corticosteroids (e.g. for asthma/chronic obstructive pulmonary disease) is acceptable.
• Change in dose of thyroid hormones within 6 weeks prior to Visit 1A or planned change or initiation of such therapy before Visit 2
• Known hypersensitivity or allergy to the investigational products or their excipients
• Impaired renal function defined as estimated Glomerular Filtration Rate (eGFR) < 60 ml/min/1.73m² (according to Zappitelli formula) as measured by the central laboratory at Visit 1A
• Indication of liver disease defined by serum level of either alanine transaminase (ALT), aspartate transaminase (AST) or alkaline phosphatase above 3 fold upper limit of normal (ULN) at Visit 1A as measured by the central laboratory at Visit 1A
• History of belonephobia (needle phobia)
• Any documented active or suspected malignancy or history of malignancy within 5 years prior to Visit 1A, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix
• Blood dyscrasias or any disorders causing haemolysis or unstable red blood cells (e.g. malaria, babesiosis, haemolytic anaemia)
• Any other acute or chronic medical or psychiatric condition or laboratory abnormality that, based on investigator's judgement, would jeopardize patient safety during trial participation or would affect the study outcome
• Medical contraindications to metformin according to the local label (for patient on metformin background therapy)
• Patient not able or cannot be supported by his/her parent(s) or legal guardian to understand and comply with study requirements based on investigator's judgement
• Previous randomisation in this trial
• Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s)
• Chronic alcohol or drug abuse within 3 months prior to Visit 1A or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial
• Female patients who are pregnant, nursing, or who plan to become pregnant in the trial