Diabetes Mellitus, Type 2Phase 1NCT02121483

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

A Phase 1 study testing empagliflozin medium dose, empagliflozin high dose and empagliflozin low dose in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 11 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The aim of the study is to generate pharmacokinetic and pharmacodynamic data to identify the safe-effective dose of empagliflozin in children and adolescents aged 10 to less than 18 years with type 2 diabetes mellitus. Read more about this study

Who is it for?: Ages 10 to 17 years
Conditions the study is for: Diabetes Mellitus, Type 2
What is being tested?: empagliflozin medium dose, empagliflozin high dose and empagliflozin low dose
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 27 participants
Where: 11 sitesin 5 countries
Study dates: Jun 2014to Feb 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 10 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Children and adolescents with type 2 diabetes mellitus
Insufficient glycaemic control (HbA1c <=10.5%) despite diet and exercise and/or metformin and/or stable basal or MDI insulin
Negative for Islet Cell Antigen and Glutamic Acid Decarboxylase autoantibodies and fasting C-peptide levels >= 0.85 ng/ml
BMI > 50th percentile for age and sex

Who cannot join

Uncontrolled hyperglycaemia with a glucose level > 240 mg/dl (> 13.3 mmol/l)
History of acute metabolic decompensation such as diabetic ketoacidosis within 3 months before the screening visit with the exception of acute de-compensation at the time of type 2 diabetes diagnosis
Treatment with weight reduction medications within 4 weeks before randomisation

Trial locations and contacts

11 sites in 5 countries.

Country

City, postcode or hospital

11 sites in 5 countries

United States5 sites

1245.87.01004 Boehringer Ingelheim Investigational Site
Boston, Massachusetts
1245.87.01013 Boehringer Ingelheim Investigational Site
New Haven, Connecticut
1245.87.01012 Boehringer Ingelheim Investigational Site
Philadelphia, Pennsylvania
1245.87.01001 Boehringer Ingelheim Investigational Site
Pittsburgh, Pennsylvania
1245.87.01002 Boehringer Ingelheim Investigational Site
Toledo, Ohio

Other trials in United States

Israel2 sites

1245.87.97202 Boehringer Ingelheim Investigational Site
Beersheba
1245.87.97203 Boehringer Ingelheim Investigational Site
Tel HaShomer

Other trials in Israel

South Africa2 sites

1245.87.27003 Boehringer Ingelheim Investigational Site
Bellville
1245.87.27002 Boehringer Ingelheim Investigational Site
Pretoria

Other trials in South Africa

France1 site

1245.87.33001 Boehringer Ingelheim Investigational Site
Lyon

Other trials in France

Mexico1 site

1245.87.52001 Boehringer Ingelheim Investigational Site
Chihuahua City

Other trials in Mexico

About this study

Official title: An Open-label, Randomised, Multicentre, Single-dose, Parallel Group Trial to Evaluate Pharmacokinetics and Pharmacodynamics of Empagliflozin in Children and Adolescents From 10 to Less Than 18 Years of Age With Type 2 Diabetes Mellitus

Conditions: Diabetes Mellitus, Type 2
Being tested: empagliflozin medium dose, empagliflozin high dose, empagliflozin low dose
Medical subject headings: Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

empagliflozin medium doseDrug
empagliflozin high doseDrug
empagliflozin low doseDrug

Study groups in NCT02121483
Study group	Role	What they receive
empagliflozin high dose	Experimental	Patient to receive a high dose of empagliflozin Receives: Drug: empagliflozin high dose
empagliflozin medium dose	Experimental	Patient to receive a medium dose of empagliflozin Receives: Drug: empagliflozin medium dose
empagliflozin low dose	Experimental	Patient to receive a low dose of empagliflozin Receives: Drug: empagliflozin low dose

What is being measured

The primary outcome is the main question the study is designed to answer.

AUC0-inf
Area under the concentration-time curve of analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf).
Measured: 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.
AUC0-tz
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).
Measured: 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.
Cmax
Maximum measured concentration in plasma (Cmax).
Measured: 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.
Tmax
Maximum measured concentration in plasma (tmax).
Measured: 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.
t1/2
Terminal half-life in plasma (t1/2).
Measured: 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.

Secondary outcomes (3)

Change From Baseline in Urinary Glucose Excretion (UGE) Over 24 h After Study Drug Intake
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.
Measured: baseline and 24 hours
Change From Baseline in Fasting Plasma Glucose (FPG) at 24 h After Study Drug Intake
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.
Measured: baseline and 24 hours
Change From Baseline in 8-point Plasma Glucose Profile Over 24 h After Study Drug Intake
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.
Measured: baseline and 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2014Feb 2016

First posted23 Apr 2014 (estimated)
Study startJun 2014
Primary completionFeb 2016
Study completionFeb 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 27 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02121483
Sponsor's protocol ID: 1245.87
Other IDs: 2013-002304-14
Status last verified: Jul 2016
First submitted: 22 Apr 2014
Last updated: 19 Sep 2016
Results posted: Yes, on ClinicalTrials.gov

Publications

Bjornstad P, Laffel L, Tamborlane WV, Simons G, Hantel S, von Eynatten M, George J, Marquard J, Cherney DZI. Acute Effect of Empagliflozin on Fractional Excretion of Sodium and eGFR in Youth With Type 2 Diabetes. Diabetes Care. 2018 Aug;41(8):e129-e130. doi: 10.2337/dc18-0394. Epub 2018 Jun 25. No abstract available.
PubMed 29941496
Laffel LMB, Tamborlane WV, Yver A, Simons G, Wu J, Nock V, Hobson D, Hughan KS, Kaspers S, Marquard J. Pharmacokinetic and pharmacodynamic profile of the sodium-glucose co-transporter-2 inhibitor empagliflozin in young people with Type 2 diabetes: a randomized trial. Diabet Med. 2018 Aug;35(8):1096-1104. doi: 10.1111/dme.13629. Epub 2018 May 6.
PubMed 29655290

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

All Diabetes Mellitus, Type 2 trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Randomised, Multicentre, Single-dose, Parallel Group Trial to Evaluate Pharmacokinetics and Pharmacodynamics of Empagliflozin in Children and Adolescents From 10 to Less Than 18 Years of Age With Type 2 Diabetes Mellitus
ClinicalTrials.gov ID: NCT02121483
Acronym / sponsor ID: 1245.87
Conditions: Diabetes Mellitus, Type 2
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 27 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: Jun 2014
Primary completion: Feb 2016 (actual)
Study completion: Feb 2016 (actual)
First posted: 23 Apr 2014 (estimated)
Results: Posted 19 Sep 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
empagliflozin high dose	Experimental	Drug: empagliflozin high dosePatient to receive a high dose of empagliflozin
empagliflozin medium dose	Experimental	Drug: empagliflozin medium dosePatient to receive a medium dose of empagliflozin
empagliflozin low dose	Experimental	Drug: empagliflozin low dosePatient to receive a low dose of empagliflozin

Who may qualify

Ages: 10 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (4 listed)

Children and adolescents with type 2 diabetes mellitus
Insufficient glycaemic control (HbA1c <=10.5%) despite diet and exercise and/or metformin and/or stable basal or MDI insulin
Negative for Islet Cell Antigen and Glutamic Acid Decarboxylase autoantibodies and fasting C-peptide levels >= 0.85 ng/ml
BMI > 50th percentile for age and sex

Key exclusion criteria (3 listed)

Uncontrolled hyperglycaemia with a glucose level > 240 mg/dl (> 13.3 mmol/l)
History of acute metabolic decompensation such as diabetic ketoacidosis within 3 months before the screening visit with the exception of acute de-compensation at the time of type 2 diabetes diagnosis
Treatment with weight reduction medications within 4 weeks before randomisation

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
empagliflozin medium dose	Drug	empagliflozin medium dose
empagliflozin high dose	Drug	empagliflozin high dose
empagliflozin low dose	Drug	empagliflozin low dose

Primary outcome

AUC0-inf
Time frame: 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.
Area under the concentration-time curve of analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-inf).
AUC0-tz
Time frame: 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.
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).
Cmax
Time frame: 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.
Maximum measured concentration in plasma (Cmax).
Tmax
Time frame: 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.
Maximum measured concentration in plasma (tmax).
t1/2
Time frame: 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.
Terminal half-life in plasma (t1/2).

3 secondary outcomes

Change From Baseline in Urinary Glucose Excretion (UGE) Over 24 h After Study Drug Intake
Time frame: baseline and 24 hours
Change From Baseline in Fasting Plasma Glucose (FPG) at 24 h After Study Drug Intake
Time frame: baseline and 24 hours
Change From Baseline in 8-point Plasma Glucose Profile Over 24 h After Study Drug Intake
Time frame: baseline and 24 hours

Results and safety

Results posted to the registry on 19 Sep 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Empagliflozin 5mg	9	9
Empagliflozin 10mg	8	8
Empagliflozin 25mg	10	10

Primary outcome: AUC0-inf

Time frame: 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.. Geometric mean (Geometric Coefficient of Variation). Unit: nmol*h/L

Measure	Empagliflozin 5mg n = 9	Empagliflozin 10mg n = 8	Empagliflozin 25mg n = 10
Value	1150 (47.6)	1430 (17.2)	5060 (29.5)

Empagliflozin 5mg vs Empagliflozin 10mg vs Empagliflozin 25mg: Slope: 0.9490 (95% CI 0.7276 to 1.1704)

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

Primary outcome: AUC0-tz

Measure	Empagliflozin 5mg n = 9	Empagliflozin 10mg n = 8	Empagliflozin 25mg n = 10
Value	1110 (49.9)	1400 (17.1)	4980 (29.1)

Empagliflozin 5mg vs Empagliflozin 10mg vs Empagliflozin 25mg: Slope: 0.9597 (95% CI 0.7356 to 1.1838)

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

Primary outcome: Cmax

Measure	Empagliflozin 5mg n = 9	Empagliflozin 10mg n = 8	Empagliflozin 25mg n = 10
Value	159 (44.5)	188 (50.2)	602 (61.1)

Empagliflozin 5mg vs Empagliflozin 10mg vs Empagliflozin 25mg: Slope: 0.8554 (95% CI 0.5504 to 1.1603)

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

Primary outcome: Tmax

Measure	Empagliflozin 5mg n = 9	Empagliflozin 10mg n = 8	Empagliflozin 25mg n = 10
Value	1.50 (0.95 to 7.92)	1.25 (0.97 to 4.17)	1.78 (0.50 to 4.00)

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

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: All adverse events reported within 7 days following trial drug administration were considered on treatment, up to 8 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Empagliflozin 5mg	0 of 9 (0%)	4 of 9 (44.4%)	Not reported
Empagliflozin 10mg	0 of 8 (0%)	1 of 8 (12.5%)	Not reported
Empagliflozin 25mg	0 of 10 (0%)	2 of 10 (20%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29941496Bjornstad P, Laffel L, Tamborlane WV, Simons G, Hantel S, von Eynatten M, George J, Marquard J, Cherney DZI. Acute Effect of Empagliflozin on Fractional Excretion of Sodium and eGFR in Youth With Type 2 Diabetes. Diabetes Care. 2018 Aug;41(8):e129-e130. doi: 10.2337/dc18-0394. Epub 2018 Jun 25. No abstract available.
Derived from this study: PubMed 29655290Laffel LMB, Tamborlane WV, Yver A, Simons G, Wu J, Nock V, Hobson D, Hughan KS, Kaspers S, Marquard J. Pharmacokinetic and pharmacodynamic profile of the sodium-glucose co-transporter-2 inhibitor empagliflozin in young people with Type 2 diabetes: a randomized trial. Diabet Med. 2018 Aug;35(8):1096-1104. doi: 10.1111/dme.13629. Epub 2018 May 6.

Related trials for Diabetes Mellitus, Type 2

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

11 sites in 5 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing empagliflozin medium dose, empagliflozin high dose and empagliflozin low dose in people with Diabetes Mellitus, Type 2, run by Boehringer Ingelheim at 11 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Israel, South Africa, France, Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUC0-inf (time frame: 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.). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02121483, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2016.