Trial Outcomes & Findings for Finding a Safe and Effective Dose of Linagliptin in Pediatric Patients With Type 2 Diabetes (NCT NCT01342484)

Last Updated: 2016-09-15

Results Overview

Change from baseline in Glycosylated haemoglobin (HbA1c) \[%\] after 12 weeks of treatment with double-blind trial medication. Baseline was defined as the last observation before the first intake of any double-blind randomised trial medication. The number of participants analysed displays the number of participants with available data at the timepoint of interest.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Baseline and 12 weeks

Results posted on

2016-09-15

Participant Flow

Randomised, double-blind, placebo-controlled parallel group dose-finding study of linagliptin over 12 weeks in children and adolescents, from 10 to 17 years of age, with type 2 diabetes mellitus. Due to serious Good clinical practice (GCP) breach, 1 patient excluded from all analyses. So protocol section has 40 subjects and participant flow has 39

All patients suitable after screening underwent a 2-week open-label placebo run-in period before randomisation. Patients who successfully completed this period and who still met the inclusion/exclusion criteria were randomised to the 12-week randomised period in which they received either 1 of the 2 doses of linagliptin or placebo.

Participant milestones

Participant milestones
Measure	Placebo Matching placebo dose was administered orally once daily for 12 weeks	Linagliptin 1 mg Linagliptin 1 mg dose was administered orally once daily for 12 weeks	Linagliptin 5 mg Linagliptin 5 mg dose was administered orally once daily for 12 weeks
Overall Study STARTED	15	10	14
Overall Study COMPLETED	13	10	13
Overall Study NOT COMPLETED	2	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching placebo dose was administered orally once daily for 12 weeks	Linagliptin 5 mg Linagliptin 5 mg dose was administered orally once daily for 12 weeks
Overall Study Other Reasons	1	0
Overall Study Protocol Violation	0	1
Overall Study Withdrawal by Subject	1	0

Baseline Characteristics

Finding a Safe and Effective Dose of Linagliptin in Pediatric Patients With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=15 Participants Matching placebo dose was administered orally once daily for 12 weeks	Linagliptin 1 mg n=10 Participants Linagliptin 1 mg dose was administered orally once daily for 12 weeks	Linagliptin 5 mg n=14 Participants Linagliptin 5 mg dose was administered orally once daily for 12 weeks	Total n=39 Participants Total of all reporting groups
Age, Continuous	13.7 Years STANDARD_DEVIATION 2.0 • n=99 Participants	14.0 Years STANDARD_DEVIATION 1.8 • n=107 Participants	14.3 Years STANDARD_DEVIATION 2.1 • n=206 Participants	14.0 Years STANDARD_DEVIATION 1.9 • n=7 Participants
Sex: Female, Male Female	8 Participants n=99 Participants	4 Participants n=107 Participants	9 Participants n=206 Participants	21 Participants n=7 Participants
Sex: Female, Male Male	7 Participants n=99 Participants	6 Participants n=107 Participants	5 Participants n=206 Participants	18 Participants n=7 Participants

PRIMARY outcome

Timeframe: Baseline and 12 weeks

Population: Full analysis set (FAS) including all randomised patients who were treated with at least one dose of study drug and had a baseline and at least one on-treatment HbA1c assessment. Observed Case (OC): In the OC analysis, values after the use of rescue medication were set to missing.

Outcome measures

Outcome measures
Measure	Placebo n=11 Participants Matching placebo dose was administered orally once daily for 12 weeks	Linagliptin 1 mg n=8 Participants Linagliptin 1 mg dose was administered orally once daily for 12 weeks	Linagliptin 5 mg n=13 Participants Linagliptin 5 mg dose was administered orally once daily for 12 weeks
Change From Baseline in Glycosylated Haemoglobin (HbA1c) (%) After 12 Weeks of Treatment	0.45 Percentage of HbA1c Standard Error 0.31	-0.03 Percentage of HbA1c Standard Error 0.38	-0.19 Percentage of HbA1c Standard Error 0.30

SECONDARY outcome

Timeframe: Baseline and 4 weeks or 8 weeks or 12 weeks

Population: Full analysis set (FAS) including all randomised patients who were treated with at least one dose of study drug and had a baseline and at least one on-treatment HbA1c assessment. OR (Original Results). The analysis excludes placebo patients and 1 FAS patient from Linagliptin 1 mg group.

DPP-4 inhibition (%) at trough at steady state is the relative change between the measurement of DPP-4 activity taken 0.5 hours before dosing at baseline and the first available on-treatment measurement of DPP-4 activity taken 0.5 hour before dosing at week 4, 8 or 12: DPP-4 inhibition (%) = 100 - (DPP-4 activity at week X / DPP-4 activity at baseline) x 100.

Outcome measures

Outcome measures
Measure	Placebo Matching placebo dose was administered orally once daily for 12 weeks	Linagliptin 1 mg n=9 Participants Linagliptin 1 mg dose was administered orally once daily for 12 weeks	Linagliptin 5 mg n=13 Participants Linagliptin 5 mg dose was administered orally once daily for 12 weeks
Dipeptidyl-peptidase-4 (DPP-4) Inhibition (%) at Trough at Steady State	—	38.4 Percentage of DPP-4 inhibition Interval 26.9 to 48.8	78.9 Percentage of DPP-4 inhibition Interval 67.7 to 84.0

SECONDARY outcome

Timeframe: Baseline and 12 weeks

Change from baseline in FPG (mmol/L) after 12 weeks of treatment with double-blind trial medication. The number of participants analysed displays the number of participants with available data at the timepoint of interest.

Outcome measures

Outcome measures
Measure	Placebo n=12 Participants Matching placebo dose was administered orally once daily for 12 weeks	Linagliptin 1 mg n=8 Participants Linagliptin 1 mg dose was administered orally once daily for 12 weeks	Linagliptin 5 mg n=13 Participants Linagliptin 5 mg dose was administered orally once daily for 12 weeks
Change From Baseline in Fasting Plasma Glucose (FPG) After 12 Weeks of Treatment	1.70 mmol/L Standard Error 0.85	1.39 mmol/L Standard Error 1.07	-0.19 mmol/L Standard Error 0.83

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Linagliptin 1 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Linagliptin 5 mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=15 participants at risk Matching placebo dose was administered orally once daily for 12 weeks	Linagliptin 1 mg n=10 participants at risk Linagliptin 1 mg dose was administered orally once daily for 12 weeks	Linagliptin 5 mg n=14 participants at risk Linagliptin 5 mg dose was administered orally once daily for 12 weeks
Metabolism and nutrition disorders Hyperglycaemia	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.

Other adverse events

Additional Information

Boehringer Ingelheim, Call Center

Boehringer Ingelheim

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=15 participants at risk Matching placebo dose was administered orally once daily for 12 weeks	Linagliptin 1 mg n=10 participants at risk Linagliptin 1 mg dose was administered orally once daily for 12 weeks	Linagliptin 5 mg n=14 participants at risk Linagliptin 5 mg dose was administered orally once daily for 12 weeks
Endocrine disorders Hyperthyroidism	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Eye disorders Eye haemorrhage	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	10.0% 1/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Gastrointestinal disorders Diarrhoea	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	10.0% 1/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Gastrointestinal disorders Lip oedema	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Gastrointestinal disorders Toothache	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Infections and infestations Conjunctivitis bacterial	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	10.0% 1/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Infections and infestations Influenza	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Infections and infestations Nasopharyngitis	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	30.0% 3/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Infections and infestations Respiratory tract infection	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Infections and infestations Vulvovaginitis	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	7.1% 1/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Injury, poisoning and procedural complications Joint injury	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Investigations Blood creatinine increased	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	10.0% 1/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	20.0% 2/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	7.1% 1/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Nervous system disorders Dizziness	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	10.0% 1/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Nervous system disorders Headache	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	28.6% 4/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Nervous system disorders Paraesthesia	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	10.0% 1/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	7.1% 1/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Reproductive system and breast disorders Menorrhagia	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	10.0% 1/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Respiratory, thoracic and mediastinal disorders Cough	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	10.0% 1/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Respiratory, thoracic and mediastinal disorders Epistaxis	6.7% 1/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	7.1% 1/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	10.0% 1/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	7.1% 1/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.
Skin and subcutaneous tissue disorders Skin hyperpigmentation	0.00% 0/15 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	0.00% 0/10 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.	7.1% 1/14 • From the first intake of study drug until 7 days after the last drug administration, up to 13 weeks.