Trial Outcomes & Findings for Pharmacokinetic Single Dose Trial of Empagliflozin in Children and Adolescents With Type 2 Diabetes Mellitus (NCT NCT02121483)

NCT ID: NCT02121483

Last Updated: 2016-09-19

Results Overview

Area under the concentration-time curve of analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 27 participants
• Primary outcome timeframe: Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration.
• Results posted on: 2016-09-19

Participant Flow

Participant milestones

Measure	Empagliflozin 5mg Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.
Overall Study STARTED	9	8	10
Overall Study COMPLETED	9	8	10
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetic Single Dose Trial of Empagliflozin in Children and Adolescents With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Empagliflozin 5mg n=9 Participants Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg n=8 Participants Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg n=10 Participants Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.	Total n=27 Participants Total of all reporting groups
Age, Continuous	13.7 Years STANDARD_DEVIATION 2.0 • n=5 Participants	14.5 Years STANDARD_DEVIATION 1.9 • n=7 Participants	14.2 Years STANDARD_DEVIATION 2.1 • n=5 Participants	14.1 Years STANDARD_DEVIATION 2.0 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants	18 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration.

Population: Pharmacokinetic Set (PKS): The PKS included all treated patients who provided at least 1 primary or secondary pharmacokinetic parameter for statistical assessment.

Area under the concentration-time curve of analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf).

Outcome measures

Measure	Empagliflozin 5mg n=9 Participants Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg n=8 Participants Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg n=10 Participants Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.
AUC0-inf	1150 nmol*h/L Geometric Coefficient of Variation 47.6	1430 nmol*h/L Geometric Coefficient of Variation 17.2	5060 nmol*h/L Geometric Coefficient of Variation 29.5

PRIMARY outcome

Timeframe: Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration.

Population: Pharmacokinetic Set (PKS): The PKS included all treated patients who provided at least 1 primary or secondary pharmacokinetic parameter for statistical assessment.

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz).

Outcome measures

Measure	Empagliflozin 5mg n=9 Participants Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg n=8 Participants Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg n=10 Participants Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.
AUC0-tz	1110 nmol*h/L Geometric Coefficient of Variation 49.9	1400 nmol*h/L Geometric Coefficient of Variation 17.1	4980 nmol*h/L Geometric Coefficient of Variation 29.1

PRIMARY outcome

Timeframe: Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration.

Population: Pharmacokinetic Set (PKS): The PKS included all treated patients who provided at least 1 primary or secondary pharmacokinetic parameter for statistical assessment.

Maximum measured concentration in plasma (Cmax).

Outcome measures

Measure	Empagliflozin 5mg n=9 Participants Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg n=8 Participants Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg n=10 Participants Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.
Cmax	159 nmol/L Geometric Coefficient of Variation 44.5	188 nmol/L Geometric Coefficient of Variation 50.2	602 nmol/L Geometric Coefficient of Variation 61.1

PRIMARY outcome

Timeframe: Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration.

Population: Pharmacokinetic Set (PKS): The PKS included all treated patients who provided at least 1 primary or secondary pharmacokinetic parameter for statistical assessment.

Maximum measured concentration in plasma (tmax).

Outcome measures

Measure	Empagliflozin 5mg n=9 Participants Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg n=8 Participants Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg n=10 Participants Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.
Tmax	1.50 hours Interval 0.95 to 7.92	1.25 hours Interval 0.97 to 4.17	1.78 hours Interval 0.5 to 4.0

PRIMARY outcome

Timeframe: Before drug administration (-0:30 hours (h)) and 0:30h, 1:00h, 1:30h, 2:00h, 4:00h, 8:00h, 12:00 (Day 1), 24:00 (Day 2), 34:00 (Day 2), 48:00 (Day 3) after drug administration.

Population: Pharmacokinetic Set (PKS): The PKS included all treated patients who provided at least 1 primary or secondary pharmacokinetic parameter for statistical assessment.

Terminal half-life in plasma (t1/2).

Outcome measures

Measure	Empagliflozin 5mg n=9 Participants Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg n=8 Participants Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg n=10 Participants Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.
t1/2	6.92 hours Geometric Coefficient of Variation 19.4 • Interval 5.46 to 8.9	7.35 hours Geometric Coefficient of Variation 29.3 • Interval 4.51 to 10.9	7.80 hours Geometric Coefficient of Variation 29.6 • Interval 4.93 to 11.1

SECONDARY outcome

Timeframe: baseline and 24 hours

Population: Treated Set (TS) including patients with UGE data on both visits

Change from baseline in Urinary Glucose Excretion (UGE) over 24 h after study drug intake.

For the changes from baseline in UGE on Day 1 (0 to 24 h postdose) , adjusted means per treatment group were to be calculated based on an ANCOVA including 'treatment' as a fixed effect and 'UGE at baseline' and 'FPG at baseline' as continuous covariates. Means presented are the adjusted means.

Outcome measures

Measure	Empagliflozin 5mg n=8 Participants Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg n=8 Participants Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg n=10 Participants Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.
Change From Baseline in Urinary Glucose Excretion (UGE) Over 24 h After Study Drug Intake	53.1 g/24h Standard Error 10.24	73.0 g/24h Standard Error 10.14	87.4 g/24h Standard Error 9.39

SECONDARY outcome

Timeframe: baseline and 24 hours

Population: Treated Set (TS) including patients with FPG data on both visits

Change from baseline in Fasting Plasma Glucose (FPG) at 24h after study drug intake.

For the change from baseline in FPG at 24 h postdose (in the morning of Day 2), adjusted means per treatment group were to be calculated based on an ANCOVA including 'treatment' as a fixed effect and 'FPG at baseline' as continuous covariate.

Means presented are the adjusted means.

Outcome measures

Measure	Empagliflozin 5mg n=7 Participants Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg n=8 Participants Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg n=10 Participants Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.
Change From Baseline in Fasting Plasma Glucose (FPG) at 24 h After Study Drug Intake	-15.5 mg/dL Standard Error 6.53	-16.6 mg/dL Standard Error 6.29	-20.4 mg/dL Standard Error 5.68

SECONDARY outcome

Timeframe: baseline and 24 hours

Population: Treated Set (TS) including patients with plasma glucose profile data on both visits

Change from baseline in 8-point plasma glucose profile over 24h after study drug intake (as defined by change from baseline in Mean Daily Glucose (MDG) calculated at Day 1).

For the changes from baseline in MDG on Day 1, adjusted means per treatment group were to be calculated based on an ANCOVA including 'treatment' as fixed effect and 'MDG at baseline' as continuous covariate.

Means presented are the adjusted means.

Outcome measures

Measure	Empagliflozin 5mg n=5 Participants Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg n=4 Participants Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg n=7 Participants Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.
Change From Baseline in 8-point Plasma Glucose Profile Over 24 h After Study Drug Intake	-12.9 mg/dL Standard Error 7.95	-6.5 mg/dL Standard Error 9.21	-13.2 mg/dL Standard Error 7.00

Adverse Events

Empagliflozin 5mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Empagliflozin 10mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Empagliflozin 25mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Empagliflozin 5mg n=9 participants at risk Single dose (1 tablet) of 5mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 10mg n=8 participants at risk Single dose (1 tablet) of 10mg, empagliflozin, film-coated tablet administered orally.	Empagliflozin 25mg n=10 participants at risk Single dose (1 tablet) of 25mg, empagliflozin, film-coated tablet administered orally.
Gastrointestinal disorders Abdominal pain	0.00% 0/9 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/8 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	10.0% 1/10 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days
Gastrointestinal disorders Anal pruritus	11.1% 1/9 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/8 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/10 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days
Gastrointestinal disorders Diarrhoea	0.00% 0/9 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/8 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	10.0% 1/10 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days
Gastrointestinal disorders Vomiting	11.1% 1/9 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/8 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/10 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days
Infections and infestations Nasopharyngitis	11.1% 1/9 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/8 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/10 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/9 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/8 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	10.0% 1/10 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days
Metabolism and nutrition disorders Dehydration	0.00% 0/9 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	12.5% 1/8 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/10 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days
Nervous system disorders Headache	11.1% 1/9 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	0.00% 0/8 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days	10.0% 1/10 • All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim (BI)

Phone: 1800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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