A double-blind, randomised, placebo-controlled, parallel group trial to evaluate the efficacy and safety of empagliflozin and linagliptin over 26 weeks, with a double-blind active treatment safety extension period up to 52 weeks, in children and adolescents with type 2 diabetes mellitus
- Conditions
- diabetesDiabetes mellitus type 210018424
- Registration Number
- NL-OMON55783
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 2
1. Patients aged 10 to 17 years (inclusive) at the time of randomisation (Visit
2)
2. Male and female patients
3. Women of childbearing potential (WOCBP)1 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 as well as in
Section 4.2.2.3.
4. 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)
5. Documented diagnosis of T2DM for at least 8 weeks at Visit 1A
6. Insufficient glycaemic control as measured by the central laboratory at
Visit 1A:
a. DINAMOTM: HbA1c >= 6.5% and <= 10.5%
b. DINAMOTM Mono: HbA1c >= 6.5% and <= 9.0%
7. a. DINAMOTM: Patients treated with
- diet and exercise plus metformin at least 1000 mg/day (or up to a maximal
tolerated dose) 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
b. DINAMOTM Mono: Drug-naïve patients or patients not on active treatment
(including discontinuation of metformin for at least 12 weeks prior to Visit 2)
8. BMI >= 85th percentile for age and sex according to WHO references at Visit 1B
9. Non-fasting serum C-peptide levels >= 0.6 ng/ml as measured by the central
laboratory at Visit 1A
10. Negative for both islet cell antigen auto-antibodies (IA-2) and glutamic
acid decarboxylase (GAD) auto-antibodies as measured by the central laboratory
at Visit 1A
11. Compliance with trial medication intake must be between 75% and 125% during
the open-label placebo run-in period
1. 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)
2. Diagnosis of monogenic diabetes (e.g. MODY)
3. History of pancreatitis
4. Diagnosis of metabolic bone disease
5. Gastrointestinal disorders that might interfere with study drug absorption
according to investigator assessment
6. Secondary obesity as part of a syndrome (e.g. Prader-Willi syndrome)
7. Any antidiabetic medication (with the exception of metformin and/or insulin
background therapy for DINAMOTM) within 8 weeks prior to Visit 1A and until
Visit 2
8. Treatment with weight reduction medications (including anti-obesity drugs)
within 3 months prior to Visit 1A and until Visit 2
9. History of weight-loss surgery or current aggressive diet regimen (according
to investigator assessment) at Visit 1A and until Visit 2
10. 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.
11. Change in dose of thyroid hormones within 6 weeks prior to Visit 1A or
planned change or initiation of such therapy before Visit 2
12. Known hypersensitivity or allergy to the investigational products or their
excipients
13. 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
14. 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
15. History of belonephobia (needle phobia)
16. 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 situcarcinoma of uterine cervix
17. Blood dyscrasias or any disorders causing haemolysis or unstable red blood
cells (e.g. malaria, babesiosis, haemolytic anaemia)
18. 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
19. Medical contraindications to metformin according to the local label (for
patient on metformin background therapy)
20. 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
21. Previous randomisation in this trial
22. 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)
23. 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
24. Female patients who are pregnant, nursing, or who plan to become pregnant
in the trial
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>DINAMOTM<br /><br>The primary efficacy endpoint will be the change in HbA1c (%) from baseline to<br /><br>the end of 26 weeks.<br /><br><br /><br>DINAMOTM Mono<br /><br>The primary efficacy endpoint will be the occurrence of treatment failure up to<br /><br>or at Week 26 as a binary endpoint, defined as meeting at least one of the<br /><br>following criteria:<br /><br>* Use of rescue medication at any time up to Week 26<br /><br>* Increase from baseline in HbA1c by 0.5% at Week 26<br /><br>* Increase from baseline in HbA1c to above 7.0% at Week 26 in patients with<br /><br>baseline HbA1c < 7.0%.<br /><br><br /><br>See protocol section 5.1.1</p><br>
- Secondary Outcome Measures
Name Time Method