HealthyPhase 1NCT01634100

Drug-interaction Trial in Healthy Subjects With Oral Administration of Empagliflozin (BI 10773), Rifampicin and Probenecid

A Phase 1 study testing Probenecid, Rifampicin and Empagliflozin in people with Healthy, run by Boehringer Ingelheim at 1 site in Germany.

Completed

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

Official record

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Trial summary

The objectives of the trial are to investigate the effect of concurrent administration of rifampicin and probenecid on the pharmacokinetics of empagliflozin. Read more about this study

Who is it for?: Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Probenecid, Rifampicin and Empagliflozin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 18 participants
Where: 1 siteGermany
Study dates: Jun 2012to Aug 2012
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 18 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

1. healthy male and female subjects

Who cannot join

1. any relevant deviation from healthy conditions

Trial locations and contacts

1 site in 1 country.

Germany1 site

1245.83.1 Boehringer Ingelheim Investigational Site
Biberach

Other trials in Germany

About this study

Official title: A Randomised, Open-label, Three-way Crossover Trial to Investigate the Effect of Rifampicin and Probenecid on Empagliflozin Pharmacokinetics in Healthy Male and Female Subjects

The objectives of the trial are to investigate the effect of concurrent administration of rifampicin and probenecid on the pharmacokinetics of empagliflozin.

Conditions: Healthy
Being tested: Probenecid, Rifampicin, Empagliflozin, Empagliflozin (BI 10773)

What participants receive

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

ProbenecidDrug
Probenecid
RifampicinDrug
Rifampicin
EmpagliflozinDrug
BI Drug
EmpagliflozinDrug
BI Drug
RifampicinDrug
Rifampicin
ProbenecidDrug
Probenecid
Empagliflozin (BI 10773)Drug
BI Drug

Study groups in NCT01634100
Study group	Role	What they receive
A (Reference)	Experimental	Empagliflozin (BI 10773), Film-coated tablet, single dose Receives: Drug: Probenecid; Drug: Empagliflozin; Drug: Rifampicin
B (Test 1)	Experimental	Empagliflozin (BI 10773), Film-coated tablet, single dose, and Rifampicin,Film-coated tablet single dose Receives: Drug: Rifampicin; Drug: Empagliflozin
C (Test 2)	Experimental	Empagliflozin (BI 10773), Film-coated tablet, single dose, and Probenecid Tablet twice daily Receives: Drug: Probenecid; Drug: Empagliflozin (BI 10773)

What is being measured

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

Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞)
Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity.
Measured: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose
Total Empa: Maximum Measured Concentration (Cmax)
Maximum measured concentration of total empa in plasma, per period.
Measured: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose

Secondary outcomes (1)

Total Empagliflozin: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz)
Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to the time of last the quantifiable data point.
Measured: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose

Timeline

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

Jun 2012Aug 2012

First posted6 Jul 2012 (estimated)
Study startJun 2012
Primary completionAug 2012
Study completionAug 2012

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 (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies 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: Crossover
Masking: None (open label)
Enrolment: 18 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01634100
Sponsor's protocol ID: 1245.83
Other IDs: 2012-000971-17
Status last verified: Jun 2014
First submitted: 3 Jul 2012
Last updated: 3 Jul 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

Macha S, Koenen R, Sennewald R, Schone K, Hummel N, Riedmaier S, Woerle HJ, Salsali A, Broedl UC. Effect of gemfibrozil, rifampicin, or probenecid on the pharmacokinetics of the SGLT2 inhibitor empagliflozin in healthy volunteers. Clin Ther. 2014 Feb 1;36(2):280-90.e1. doi: 10.1016/j.clinthera.2014.01.003. Epub 2014 Feb 1.
PubMed 24491572

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

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All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 3 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Open-label, Three-way Crossover Trial to Investigate the Effect of Rifampicin and Probenecid on Empagliflozin Pharmacokinetics in Healthy Male and Female Subjects
ClinicalTrials.gov ID: NCT01634100
Acronym / sponsor ID: 1245.83
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 18 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Jun 2012
Primary completion: Aug 2012 (actual)
Study completion: Aug 2012 (actual)
First posted: 6 Jul 2012 (estimated)
Results: Posted 3 Jul 2014

Clinical summary

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

The objectives of the trial are to investigate the effect of concurrent administration of rifampicin and probenecid on the pharmacokinetics of empagliflozin.

Study design

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

Arm	Type	Receives
A (Reference)	Experimental	Drug: Probenecid, Drug: Empagliflozin, Drug: RifampicinEmpagliflozin (BI 10773), Film-coated tablet, single dose
B (Test 1)	Experimental	Drug: Rifampicin, Drug: EmpagliflozinEmpagliflozin (BI 10773), Film-coated tablet, single dose, and Rifampicin,Film-coated tablet single dose
C (Test 2)	Experimental	Drug: Probenecid, Drug: Empagliflozin (BI 10773)Empagliflozin (BI 10773), Film-coated tablet, single dose, and Probenecid Tablet twice daily

Who may qualify

Ages: 18 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

1. healthy male and female subjects

Key exclusion criteria (1 listed)

1. any relevant deviation from healthy conditions

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
ProbenecidProbenecid	Drug	A (Reference)
RifampicinRifampicin	Drug	B (Test 1)
EmpagliflozinBI Drug	Drug	A (Reference)
EmpagliflozinBI Drug	Drug	B (Test 1)
RifampicinRifampicin	Drug	A (Reference)
ProbenecidProbenecid	Drug	C (Test 2)
Empagliflozin (BI 10773)BI Drug	Drug	C (Test 2)

Primary outcome

Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞)
Time frame: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose
Area under the concentration-time curve of total empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity.
Total Empa: Maximum Measured Concentration (Cmax)
Time frame: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose
Maximum measured concentration of total empa in plasma, per period.

1 secondary outcome

Total Empagliflozin: Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz)
Time frame: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose

Results and safety

Results posted to the registry on 3 Jul 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Empa Alone / Empa + Rifampicin / Empa + Probenecid	3	2
Empa Alone / Empa + Probenecid / Empa + Rifampicin	3	3
Empa + Rifampicin / Empa Alone / Empa + Probenecid	3	2
Empa + Rifampicin / Empa + Probenecid / Empa Alone	3	3
Empa + Probenecid / Empa Alone / Empa + Rifampicin	3	3
Empa + Probenecid / Empa + Rifampicin / Empa Alone	3	3

Primary outcome: Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞)

Time frame: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose. Geometric mean (Geometric Coefficient of Variation). Unit: nmol*h/L

Measure	Empa Alone n = 18	Empa + Rifampicin n = 18	Empa + Probenecid n = 16
Value	2240 (28.1)	3020 (28.2)	3400 (28.7)

Empa Alone vs Empa + Rifampicin: Geometric Mean Ratio: 135.20 (90% CI 129.58 to 141.06), ANOVA
Empa Alone vs Empa + Probenecid: Geometric Mean Ratio: 153.47 (90% CI 146.41 to 160.88), ANOVA

Population analysed: Pharmacokinetic (PK) set: The PK analysis set includes all subjects who took at least 1 dose of investigational treatment and provided at least 1 evaluable observation for at least 1 primary PK endpoint in at least 1 treatment period without any important protocol violations relevant to the evaluation of PK.

Primary outcome: Total Empa: Maximum Measured Concentration (Cmax)

Measure	Empa Alone n = 18	Empa + Rifampicin n = 18	Empa + Probenecid n = 16
Value	301 (31.6)	527 (27.5)	373 (30.9)

Empa Alone vs Empa + Rifampicin: Geometric Mean Ratio: 175.14 (90% CI 160.14 to 191.56), ANOVA
Empa Alone vs Empa + Probenecid: Geometric Mean Ratio: 125.60 (90% CI 113.67 to 138.78), ANOVA

1 secondary outcome is reported in the full results.

Adverse events

Time frame: Treatment period until end of washout period/end of study examination, up to 29 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Empa Alone	0 of 18 (0%)	7 of 18 (38.9%)	Not reported
Empa + Rifampicin	0 of 18 (0%)	9 of 18 (50%)	Not reported
Empa + Probenecid	0 of 16 (0%)	6 of 16 (37.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jul 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24491572Macha S, Koenen R, Sennewald R, Schone K, Hummel N, Riedmaier S, Woerle HJ, Salsali A, Broedl UC. Effect of gemfibrozil, rifampicin, or probenecid on the pharmacokinetics of the SGLT2 inhibitor empagliflozin in healthy volunteers. Clin Ther. 2014 Feb 1;36(2):280-90.e1. doi: 10.1016/j.clinthera.2014.01.003. Epub 2014 Feb 1.
Related InfoLink provided by the sponsor.

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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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Probenecid, Rifampicin and Empagliflozin in people with Healthy, run by Boehringer Ingelheim at 1 site in Germany.

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 1 inclusion and 1 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 3 Jul 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. 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 3 Jul 2014). 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?

Total Empagliflozin: Area Under the Curve 0 to Infinity (AUC0-∞) (time frame: 15 minutes (min) prior to the first dose and 20min, 40min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h, 36h, 48h and 72h after the first dose). The study lists 2 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 NCT01634100, which also lists 1 linked publication.

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 3 Jul 2014.