HealthyPhase 1NCT02084082

Bioequivalence of a FDC Tablet of Linagliptin/Metformin (5mg/1000mg) Extended Release in Healthy Subjects

A Phase 1 study testing Linagliptin/Metformin ER FDC, Linagliptin and Metformin ER 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

Search all trials

Trial summary

The purpose of this trial is to demonstrate bioequivalence of a newly developed fixed dose combination (FDC) tablet containing linagliptin and metformin extended release compared to the free combination of linagliptin and metformin extended release, both under fed and fasted conditions. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Linagliptin/Metformin ER FDC, Linagliptin and Metformin ER
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 68 participants
Where: 1 siteGermany
Study dates: Apr 2014to Jul 2014
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 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy male or female subjects

Who cannot join

Any relevant deviation from healthy condition

Trial locations and contacts

1 site in 1 country.

Germany1 site

1288.9.1 Boehringer Ingelheim Investigational Site
Biberach

Other trials in Germany

About this study

Official title: Bioequivalence of a Fixed Dose Combination Tablet of Linagliptin/Metformin Extended Release (5 mg/1000 mg) Compared With the Free Combination of Linagliptin and Metformin Extended Release Tablets in Healthy Subjects (an Open-label, Randomised, Single Dose, Two-way Crossover Trial)

Conditions: Healthy
Being tested: Linagliptin/Metformin ER FDC, Linagliptin, Metformin ER

What participants receive

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

Linagliptin/Metformin ER FDCDrug
1x Linagliptin/Metformin FDC tablet
LinagliptinDrug
1x Linagliptin tablet
Metformin ERDrug
2x Metformin ER tablets

Study groups in NCT02084082
Study group	Role	What they receive
FDC first, fasted	Experimental	Linagliptin/Metformin ER FDC followed by single tablets of linagliptin and metformin ER, fasted condition Receives: Drug: Linagliptin/Metformin ER FDC; Drug: Linagliptin; Drug: Metformin ER
Single tablets first, fasted	Experimental	single tablets of linagliptin and metformin ER followed by Linagliptin/Metformin ER FDC, fasted condition Receives: Drug: Linagliptin/Metformin ER FDC; Drug: Linagliptin; Drug: Metformin ER
FDC first, fed	Experimental	Linagliptin/Metformin ER FDC followed by single tablets of linagliptin and metformin ER, fed condition Receives: Drug: Linagliptin/Metformin ER FDC; Drug: Linagliptin; Drug: Metformin ER
Single tablets first, fed	Experimental	single tablets of linagliptin and metformin ER followed by Linagliptin/Metformin ER FDC, fed condition Receives: Drug: Linagliptin/Metformin ER FDC; Drug: Linagliptin; Drug: Metformin ER

What is being measured

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

Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72)
AUC 0-72 (area under concentration-time curve of the Linagliptin in plasma from 0 to 72 hours) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Measured: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Maximum Measured Concentration of Linagliptin in Plasma (Cmax)
Cmax (maximum measured concentration of Linagliptin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Measured: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
AUC 0-t (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Measured: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Cmax of Metformin in Plasma
Cmax (maximum measured concentration of the Metformin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Measured: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration

Secondary outcomes (2)

Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Linagliptin.
The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Measured: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
AUC0-inf of Metformin in Plasma
AUC0-inf(area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Metformin.
The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Measured: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration

Timeline

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

Apr 2014Jul 2014

First posted11 Mar 2014 (estimated)
Study startApr 2014
Primary completionJul 2014
Study completionJul 2014

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.
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: 68 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02084082
Sponsor's protocol ID: 1288.9
Other IDs: 2013-005142-11
Status last verified: Aug 2015
First submitted: 7 Mar 2014
Last updated: 4 Aug 2016
Results posted: Yes, on ClinicalTrials.gov

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

Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis

All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Bioequivalence of a Fixed Dose Combination Tablet of Linagliptin/Metformin Extended Release (5 mg/1000 mg) Compared With the Free Combination of Linagliptin and Metformin Extended Release Tablets in Healthy Subjects (an Open-label, Randomised, Single Dose, Two-way Crossover Trial)
ClinicalTrials.gov ID: NCT02084082
Acronym / sponsor ID: 1288.9
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 68 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Collaborators: Eli Lilly and Company
Study start: Apr 2014
Primary completion: Jul 2014 (actual)
Study completion: Jul 2014 (actual)
First posted: 11 Mar 2014 (estimated)
Results: Posted 4 Aug 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: Crossover
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
FDC first, fasted	Experimental	Drug: Linagliptin/Metformin ER FDC, Drug: Linagliptin, Drug: Metformin ERLinagliptin/Metformin ER FDC followed by single tablets of linagliptin and metformin ER, fasted condition
Single tablets first, fasted	Experimental	Drug: Linagliptin/Metformin ER FDC, Drug: Linagliptin, Drug: Metformin ERsingle tablets of linagliptin and metformin ER followed by Linagliptin/Metformin ER FDC, fasted condition
FDC first, fed	Experimental	Drug: Linagliptin/Metformin ER FDC, Drug: Linagliptin, Drug: Metformin ERLinagliptin/Metformin ER FDC followed by single tablets of linagliptin and metformin ER, fed condition
Single tablets first, fed	Experimental	Drug: Linagliptin/Metformin ER FDC, Drug: Linagliptin, Drug: Metformin ERsingle tablets of linagliptin and metformin ER followed by Linagliptin/Metformin ER FDC, fed condition

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (1 listed)

Healthy male or female subjects

Key exclusion criteria (1 listed)

Any relevant deviation from healthy condition

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
Linagliptin/Metformin ER FDC1x Linagliptin/Metformin FDC tablet	Drug	FDC first, fasted, FDC first, fed, Single tablets first, fasted, Single tablets first, fed
Linagliptin1x Linagliptin tablet	Drug	FDC first, fasted, FDC first, fed, Single tablets first, fasted, Single tablets first, fed
Metformin ER2x Metformin ER tablets	Drug	FDC first, fasted, FDC first, fed, Single tablets first, fasted, Single tablets first, fed

Primary outcome

Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72)
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
AUC 0-72 (area under concentration-time curve of the Linagliptin in plasma from 0 to 72 hours) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Maximum Measured Concentration of Linagliptin in Plasma (Cmax)
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Cmax (maximum measured concentration of Linagliptin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
AUC 0-t (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.
Cmax of Metformin in Plasma
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
Cmax (maximum measured concentration of the Metformin in plasma) The values for geometric mean and geometric coefficient of variation (gCV) are actually adjusted geometric means and adjusted intra-individual gCVs, respectively.

2 secondary outcomes

Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-inf)
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration
AUC0-inf of Metformin in Plasma
Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration

Results and safety

Results posted to the registry on 4 Aug 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
FDC 1000 Fast/ L+M 1000 Fast	26	26
L+M1000 Fast/ FDC1000 Fast	26	26
FDC1000 Fed/L+M1000 Fed	8	8
L+M1000 Fed/ FDC1000 Fed	8	8

Primary outcome: Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72)

Time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration. Geometric mean (Geometric Coefficient of Variation). Unit: nmol*h/L

Measure	L+M 1000 Fasted n = 52	FDC 1000 Fasted n = 52	L+M 1000 Fed n = 15	FDC 1000 Fed n = 14
Value	286.639 (11.8)	287.696 (11.8)	234.052 (9.2)	221.644 (9.2)

L+M 1000 Fasted vs FDC 1000 Fasted: Adjusted Geometric Means ratio: 100.37 (90% CI 96.562 to 104.326), p <0.0001, ANOVA
L+M 1000 Fed vs FDC 1000 Fed: Geometric mean ratio (net): 94.70 (90% CI 88.712 to 101.089), p = 0.0004, ANOVA

Population analysed: PKS 1000 fast and PKS 1000 fed, included all treated subjects in Part 1 and Part 2, respectively, who provided at least 1 observation for at least 1 primary endpoint, without important protocol violations regarding the statistical evaluation of pharmacokinetic endpoints.

Primary outcome: Maximum Measured Concentration of Linagliptin in Plasma (Cmax)

Measure	L+M 1000 Fasted n = 52	FDC 1000 Fasted n = 52	L+M 1000 Fed n = 15	FDC 1000 Fed n = 14
Value	8.826 (27.1)	9.540 (27.1)	5.791 (6.1)	5.689 (6.1)

L+M 1000 Fasted vs FDC 1000 Fasted: Adjusted Geometric Mean ratio: 108.09 (90% CI 99.022 to 117.989), p = 0.0038, ANOVA
L+M 1000 Fed vs FDC 1000 Fed: Adjusted Geometric Means ratio: 98.24 (90% CI 94.067 to 102.597), p <0.0001, ANOVA

Primary outcome: Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)

Measure	L+M 1000 Fasted n = 52	FDC 1000 Fasted n = 52	L+M 1000 Fed n = 15	FDC 1000 Fed n = 14
Value	7146.61 (22.2)	7146.00 (22.2)	11326.12 (7.1)	10980.17 (7.1)

L+M 1000 Fasted vs FDC 1000 Fasted: Adjusted Geometric Mean ratio: 99.99 (90% CI 93.03 to 107.47), p <0.0001, ANOVA
L+M 1000 Fed vs FDC 1000 Fed: Adjusted Geometric Means ratio: 96.95 (90% CI 92.24 to 101.89), p <0.0001, ANOVA

Primary outcome: Cmax of Metformin in Plasma

Measure	L+M 1000 Fasted n = 52	FDC 1000 Fasted n = 52	L+M 1000 Fed n = 15	FDC 1000 Fed n = 14
Value	925.709 (23.4)	923.543 (23.4)	947.445 (5.9)	937.685 (5.9)

L+M 1000 Fasted vs FDC 1000 Fasted: Adjusted Geometric Means ratio: 99.77 (90% CI 92.464 to 107.645), p <0.0001, ANOVA
L+M 1000 Fed vs FDC 1000 Fed: Adjusted Geometric Means ratio: 98.97 (90% CI 94.950 to 103.160), p <0.0001, ANOVA

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first drug administration for at least 7 days after the last drug administration, up to 49 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
L+M 1000 Fasted	0 of 52 (0%)	4 of 52 (7.7%)	Not reported
FDC 1000 Fasted	0 of 52 (0%)	9 of 52 (17.3%)	Not reported
L+M 1000 Fed	2 of 15 (13.3%)	4 of 15 (26.7%)	Not reported
FDC 1000 Fed	0 of 14 (0%)	4 of 14 (28.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2016.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.

Related trials for Healthy

Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis

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 Linagliptin/Metformin ER FDC, Linagliptin and Metformin ER 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 4 Aug 2016. 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 4 Aug 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?

Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) (time frame: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1h,1h 30min, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 24h,34h, 48h and 72h after drug administration). The study lists 4 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 NCT02084082.

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 4 Aug 2016.