HealthyPhase 1NCT01947153

Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto®.

A Phase 1 study testing Metformin and Linagliptin in people with Healthy, run by Boehringer Ingelheim at 1 site in Russia.

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 objective of the current study is to demonstrate bioequivalence of two 2.5 mg linagliptin/500 mg metformin fixed dose combination tablets compared to the free combination of the linagliptin 5 mg and metformin 1000 mg in healthy male and female volunteers. Read more about this study

Who is it for?: Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Metformin and Linagliptin
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 36 participants
Where: 1 siteRussia
Study dates: Nov 2013to Jan 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 45 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation
Healthy males and females according to the following criteria:
Based upon a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG and clinical laboratory tests (haematology, clinical chemistry and urinalysis).
Age 18 to 45 years (incl.)
Body mass index by Quetelet between 18.50 to 24.99 kg/m2 (incl.)
Female subjects of childbearing potential who agree on using double-barrier contraception during the study. If a female is postmenopausal (no menses for at least 2 years) or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) she will be exempt from the requirement. In case of using oral contraceptives, these should be withdrawn at least 2 months before the first drug dosing.
Male subjects who agree on using effective contraception during the study (barrier contraceptive methods)

Who cannot join

Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
Any laboratory value outside the reference range that is of clinical relevance
Any evidence of a clinically relevant concomitant disease
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Positive results of blood tests for infections (HIV, syphilis, hepatitis B or C)
A positive urine drug screening test at screening and on admission to the trial site in each treatment period.
A positive alcohol breath test at screening and on admission to the trial site in each treatment period.
Surgery of the gastrointestinal tract (except appendectomy)

Trial locations and contacts

1 site in 1 country.

Russia1 site

1288.21.1 Boehringer Ingelheim Investigational Site
Saint Petersburg

Other trials in Russia

About this study

Official title: Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto® (Two Fixed Dose Combination Tablets of Linagliptin 2.5 mg and Metformin 500 mg) Compared With the Free Combination of Linagliptin 5 mg and Metformin 1000 mg Tablets Under Fasting Conditions.

Conditions: Healthy
Being tested: Metformin, Linagliptin

What participants receive

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

MetforminDrug
Free combination
LinagliptinDrug
Fixed dose combination
MetforminDrug
Combination
LinagliptinDrug
Free combination

Study groups in NCT01947153
Study group	Role	What they receive
Fixed dose combination	Experimental	Linagliptin/Metformin Receives: Drug: Linagliptin; Drug: Metformin
Free combination	Experimental	Linagliptin and Metformin Receives: Drug: Metformin; Drug: Linagliptin

What is being measured

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

Linagliptin: AUC 0-72 (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 72 Hours)
Linagliptin:
AUC 0-72 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours)
Measured: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Metformin: 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 Data Point)
Metformin:
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 data point)
Measured: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Linagliptin: Cmax (Maximum Measured Concentration of the Analyte in Plasma)
Linagliptin:
Cmax (maximum measured concentration of the analyte in plasma)
Measured: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Metformin: Cmax (Maximum Measured Concentration of the Analyte in Plasma)
Metformin:
Cmax (maximum measured concentration of the analyte in plasma)
Measured: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Secondary outcomes (3)

Linagliptin: AUC 0-inf (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
Linagliptin:
AUC 0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Measured: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Metformin: AUC 0-inf (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity)
Metformin:
AUC 0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)
Measured: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Linagliptin: AUC 0-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 Data Point)
Linagliptin:
AUC 0-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 data point)
Measured: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 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.

Nov 2013Jan 2014

First posted20 Sep 2013 (estimated)
Study startNov 2013
Primary completionJan 2014
Study completionJan 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: 36 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01947153
Sponsor's protocol ID: 1288.21
Status last verified: Feb 2015
First submitted: 18 Sep 2013
Last updated: 25 Feb 2015
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?

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Study at a glance

From the registry record, last updated by the sponsor on 25 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Two-way Crossover Study in Healthy Male and Female Subjects to Evaluate the Bioequivalence of Jentadueto® (Two Fixed Dose Combination Tablets of Linagliptin 2.5 mg and Metformin 500 mg) Compared With the Free Combination of Linagliptin 5 mg and Metformin 1000 mg Tablets Under Fasting Conditions.
ClinicalTrials.gov ID: NCT01947153
Acronym / sponsor ID: 1288.21
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 36 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Nov 2013
Primary completion: Jan 2014 (actual)
Study completion: Jan 2014 (actual)
First posted: 20 Sep 2013 (estimated)
Results: Posted 25 Feb 2015

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: 2

Arm	Type	Receives
Fixed dose combination	Experimental	Drug: Linagliptin, Drug: MetforminLinagliptin/Metformin
Free combination	Experimental	Drug: Metformin, Drug: LinagliptinLinagliptin and Metformin

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation
Healthy males and females according to the following criteria:
Based upon a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG and clinical laboratory tests (haematology, clinical chemistry and urinalysis).
Age 18 to 45 years (incl.)
Body mass index by Quetelet between 18.50 to 24.99 kg/m2 (incl.)

Key exclusion criteria (8 listed)

Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
Any laboratory value outside the reference range that is of clinical relevance
Any evidence of a clinically relevant concomitant disease
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Positive results of blood tests for infections (HIV, syphilis, hepatitis B or C)

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
MetforminFree combination	Drug	Free combination
LinagliptinFixed dose combination	Drug	Fixed dose combination
MetforminCombination	Drug	Fixed dose combination
LinagliptinFree combination	Drug	Free combination

Primary outcome

Linagliptin: AUC 0-72 (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 72 Hours)
Time frame: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Linagliptin: AUC 0-72 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours)
Metformin: 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 Data Point)
Time frame: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Metformin: 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 data point)
Linagliptin: Cmax (Maximum Measured Concentration of the Analyte in Plasma)
Time frame: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Linagliptin: Cmax (maximum measured concentration of the analyte in plasma)
Metformin: Cmax (Maximum Measured Concentration of the Analyte in Plasma)
Time frame: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration
Metformin: Cmax (maximum measured concentration of the analyte in plasma)

3 secondary outcomes

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

Results and safety

Results posted to the registry on 25 Feb 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Fixed Dose Combination First, Then Free Combination	18	18
Free Combination First, Then Fixed Dose Combination	18	18

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

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

Measure	Fixed Dose Combination n = 36	Free Combination n = 34
Value	293 (23.4)	288 (22.9)

Fixed Dose Combination vs Free Combination: Geometric mean ratio: 102.92 (90% CI 98.370 to 107.688), p <0.0001, ANOVA

Population analysed: subject set for the evaluation of pharmacokinetic endpoints of linagliptin (PKS-L): includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for linagliptin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of linagliptin

Primary outcome: Metformin: 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 Data Point)

Measure	Fixed Dose Combination n = 36	Free Combination n = 34
Value	13000 (27.3)	12100 (24.2)

Fixed Dose Combination vs Free Combination: Geometric mean ratio: 105.14 (90% CI 99.645 to 110.941), p <0.0001, ANOVA

Population analysed: The subject set for the evaluation of pharmacokinetic endpoints of metformin (PKS-M): includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for metformin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of metformin

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

Measure	Fixed Dose Combination n = 36	Free Combination n = 34
Value	10.3 (36.4)	9.57 (36.2)

Fixed Dose Combination vs Free Combination: Geometric mean ratio: 109.05 (90% CI 98.299 to 120.968), p = 0.0014, ANOVA

Population analysed: PKS-L: includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for linagliptin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of linagliptin

Primary outcome: Metformin: Cmax (Maximum Measured Concentration of the Analyte in Plasma)

Measure	Fixed Dose Combination n = 36	Free Combination n = 34
Value	1840 (28.2)	1700 (27.0)

Fixed Dose Combination vs Free Combination: Geometric mean ratio: 105.81 (90% CI 98.471 to 113.692), p <0.0001, ANOVA

Population analysed: PKS-M: includes all subjects of the TS who provided at least 1 observation for at least 1 primary endpoint for metformin and had no important protocol violations with respect to the statistical evaluation of pharmacokinetic endpoints of metformin

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first study drug administration until 30±2 days after the last study drug administration. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Fixed Dose Combination	0 of 36 (0%)	1 of 36 (2.8%)	Not reported
Free Combination	0 of 36 (0%)	4 of 36 (11.1%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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 Metformin and Linagliptin in people with Healthy, run by Boehringer Ingelheim at 1 site in Russia.

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 7 inclusion and 8 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 25 Feb 2015. 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 Russia. 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 25 Feb 2015). 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?

Linagliptin: AUC 0-72 (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 72 Hours) (time frame: 2 hours (h) before drug administration and 20 minutes (min), 40min, 1h, 1h 30min, 2h, 3h, 4h, 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 NCT01947153.

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 25 Feb 2015.