Dose finding study of linagliptin in children and adolescents with type 2 diabetes.

Phase 1

• Conditions: Patients with type 2 diabetes.; MedDRA version: 18.0Level: LLTClassification code 10045242Term: Type II diabetes mellitusSystem Organ Class: 100000004861; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2009-017004-91-PL
• Lead Sponsor: Boehringer Ingelheim RCV GmbH & Co KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-02-28
• Last Update Posted: 8 August 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 117

Inclusion Criteria

1. Paediatric patients (children and adolescents), aged 10 to 17 years at the time of randomization (i.e. Visit 2).
2. Documented diagnosis of type 2 diabetes mellitus at least 3 months prior to randomisation (i.e. Visit 2).
3. 1. Patients with insufficient glycaemic control (i.e. an HbA1c > 6.5% and = 10.5%) at screening (i.e. Visit 1A)
3.2. Patients treated with diet and exercise and/or metformin (= 1000 mg per day (or the maximum tolerated dose) at a stable dose and dosing frequency for 8 weeks prior to randomisation) and/or concomitant stable basal insulin (total daily dose must be = 0.5U/kg with less than 10% of weekly dose
change for 12 weeks prior to randomisation).
4. Negative for islet cell antigen (ICA) auto-antibodies and glutamic acid decarboxylase (GAD) auto-antibodies prior to randomisation (i.e. Visit 2)
5. C-peptide levels (serum) = 1.5 ng/ml (at 90 min following a Boost challenge) at Visit 1B
6. Compliance during the open-label placebo run-in period between 75% and 125%.
7. BMI>50th percentile for age and sex.
8. Written informed consent provided by the patient’s parent(s) (or legal guardian) and assent by the patient at the latest by the date of Visit 1A in accordance with GCP and local legislation. Informed assent will be sought according to the patient’s age, level of maturity, competence and capacity. All informed consent/assent forms will be consistent with ICH-GCP and local IEC/IRB requirements.

Are the trial subjects under 18? yes
Number of subjects for this age range: 117
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Uncontrolled hyperglycaemia with repeatedly elevated glucose levels (i.e. at least 2 glucose levels) > 240 mg/dl (> 13.3 mmol/l)as measured by the central laboratory after an overnight fast during placebo run-in (i.e. from Visit 1B to Visit 2).
2. History of acute metabolic decompensation, such as diabetic ketoacidosis, within 3 months of screening (i.e. Visit 1A)
3. Current short-acting insulin
or having received short-acting insulin for more than 3 days within 1 month
prior to randomisation (i.e. Visit 2).
4. Treatment with weight reduction medications (including anti-obesity treatments) within 3 months prior to randomisation (i.e. the date of Visit 2)
5. Chronic treatment – treatment duration of more than two weeks - with medication known to affect glucose metabolism (e.g. metformin or systemic corticosteroids) within 3 months prior to randomisation (i.e. Visit 2)
6. Anticipated need for treatment with PGP (P-glycoprotein) and CYP 3A4 inhibitors or inducers during the placebo run-in period (Visit 1B onwards) and randomised period (Visits 2-6) of the study (See Appendix 10.5 for a list of prohibited medications)
7. Clinically significant renal disease (defined as estimated Glomerular Filtration Rate [eGFR] < 60 ml/min/1.73m2, i.e. moderate and severe renal impairment, calculated according to the Schwarz formula) as determined at screening (i.e. Visit 1A)
8. Elevated serum levels of ALT (SGPT), AST (SGOT), alkaline phosphatase above 3 x upper limit of normal (ULN) or lipase and amylase above 1.5 fold ULN as determined at screening (i.e. Visit 1A)
9. Patients with an history of documented pancreatitis
10. Gastrointestinal disorders that might interfere with study drug absorption
11. Patients presenting a secondary obesity as part of a syndrome (e.g. : Prader-Willi syndrome)
12. Female patients who are nursing or are pregnant
13. Female patients who have reached menarche (i.e. ANY vaginal bleeding, however scant or irregular) with a positive pregnancy test or who are sexually active and not using a medically accepted contraceptive method. Acceptable methods of birth control are limited to: intra-uterine device (IUD); oral, implantable or injectable contraceptives and oestrogen patch; double-barrier method (spermicide plus diaphragm); or abstinence (if permitted by local authorities) at the discretion of the Investigator
14. Patients with a history of belonephobia (needle phobia) in this age group
15. Patients with anaemia defined as shown below and as determined at screening (Visit 1A):
• children aged up to 12: haemoglobin of < 11.5 g/dl and haematocrit < 35%
• females aged > 12 or who reached menarche before this age: haemoglobin of < 12 g/dl and haematocrit < 36%
• males aged > 12: haemoglobin of < 13 g/dl and haematocrit < 39%
16. Active alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation according to the Investigator opinion
17. Patients whose parent(s) (or legal guardian) will be unable to support the reporting of adverse event information (e.g. not fluent in an appropriate language, or no access to a telephone)
18. Patients whose home circumstances will mean they are unable to store the study rescue medication (insulin) appropriately (i.e. no access to reliable refrigeration)
19. Known hypersensitivity or allergy to the investigational product or its excipients or placebo
20. Patient with an history of hereditary angioedema or history

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified