HealthyPhase 1NCT01540487

Pharmacokinetics of Fixed Dose Combination (FDC) Tablets of Linagliptin /Metformin

A Phase 1 study testing linagliptin/metformin(high dose) and Linagliptin/metformin(low dose) in people with Healthy, run by Boehringer Ingelheim at 1 site in China.

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

Who is it for?: Ages 18 to 40 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: linagliptin/metformin(high dose) and Linagliptin/metformin(low dose)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 48 participants
Where: 1 siteChina
Study dates: Feb 2012to Jun 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 40 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.

China1 site

1288.5.86001 Boehringer Ingelheim Investigational Site
Beijing

Other trials in China

About this study

Official title: Characterisation of Fixed Dose Combination Tablets of Linagliptin 2.5 mg/Metformin 850 mg or Linagliptin 2.5 mg/Metformin 500 mg and Relative Oral Bioavailability Compared With Single Linagliptin 2.5 mg and Metformin 850 mg or 500 mg Tablets Administered Together to Healthy Chinese Male and Female Volunteers in an Open Label, Randomised, Single-dose, Two-way Crossover, Phase I Study

The aim of the trial is to assess the relative bioavailability of fixed dose combination tablets of linagliptin and metformin compared to the administration of two single tablets (linagliptin and metformin ) in Chinese subjects. The availability of a fixed dose combination tablet is expected to significantly enhance patients' compliance with antidiabetic treatment., in particular with concern to the frequent polypharmacy in diabetic patients.

Conditions: Healthy
Being tested: linagliptin/metformin(high dose), Linagliptin/metformin(low dose)

What participants receive

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

linagliptin/metformin(high dose)Drug
patient would take fixed dose combination tablets of linagliptin /metformin (high dose) and single linagliptin and metformin (High dose) tablets single dose in random order, and each dosage will be separated in 42 days interval.
Linagliptin/metformin(low dose)Drug
patient would take fixed dose combination tablets of linagliptin /metformin (low dose) and single linagliptin and metformin (Low dose) tablets single dose in random order, and each dosage will be separated in 42 days interval.

Study groups in NCT01540487
Study group	Role	What they receive
linagliptin/metformin(high dose)	Experimental	24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of linagliptin /metformin (high dose) and single linagliptin and metformin (high dose) tablets single dose in randomized order Receives: Drug: linagliptin/metformin(high dose)
linagliptin/metformin(low dose)	Experimental	24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of linagliptin /metformin (low dose) and single linagliptin and metformin (low dose) tablets single dose in randomized order Receives: Drug: Linagliptin/metformin(low dose)

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 0 to 72 Hours (AUC0-72)
Measured: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.
Maximum Measured Concentration (Cmax) of Linagliptin.
Measured: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval 0 to the Last Quantifiable Concentration (AUC0-tz)
Measured: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.
Maximum Measured Concentration (Cmax) of Metformin
Measured: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

Secondary outcomes (3)

Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) for Linagliptin
AUC0-infinity is based on predicted last concentration values.
Measured: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.
AUC(0-infinity) for Metformin
AUC0-infinity is based on predicted last concentration values.
Measured: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.
AUC0-tz for Linagliptin
Measured: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

Timeline

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

Feb 2012Jun 2012

First posted28 Feb 2012 (estimated)
Study startFeb 2012
Primary completionJun 2012
Study completionJun 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.
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: 48 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01540487
Sponsor's protocol ID: 1288.5
Status last verified: Jun 2013
First submitted: 23 Feb 2012
Last updated: 6 Aug 2013
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 6 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Characterisation of Fixed Dose Combination Tablets of Linagliptin 2.5 mg/Metformin 850 mg or Linagliptin 2.5 mg/Metformin 500 mg and Relative Oral Bioavailability Compared With Single Linagliptin 2.5 mg and Metformin 850 mg or 500 mg Tablets Administered Together to Healthy Chinese Male and Female Volunteers in an Open Label, Randomised, Single-dose, Two-way Crossover, Phase I Study
ClinicalTrials.gov ID: NCT01540487
Acronym / sponsor ID: 1288.5
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 48 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Feb 2012
Primary completion: Jun 2012 (actual)
Study completion: Jun 2012 (actual)
First posted: 28 Feb 2012 (estimated)
Results: Posted 6 Aug 2013

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
linagliptin/metformin(high dose)	Experimental	Drug: linagliptin/metformin(high dose)24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of linagliptin /metformin (high dose) and single linagliptin and metformin (high dose) tablets single dose in randomized order
linagliptin/metformin(low dose)	Experimental	Drug: Linagliptin/metformin(low dose)24 subjects (12 male and 12 female) will be assigned to 2 treatment sequences. cross-over design was adopted to ensure each patient would take fixed dose combination tablets of linagliptin /metformin (low dose) and single linagliptin and metformin (low dose) tablets single dose in randomized order

Who may qualify

Ages: 18 to 40 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
linagliptin/metformin(high dose)patient would take fixed dose combination tablets of linagliptin /metformin (high dose) and single linagliptin and metformin (High dose) tablets single dose in random order, and each dosage will be separated in 42 days interval.	Drug	linagliptin/metformin(high dose)
Linagliptin/metformin(low dose)patient would take fixed dose combination tablets of linagliptin /metformin (low dose) and single linagliptin and metformin (Low dose) tablets single dose in random order, and each dosage will be separated in 42 days interval.	Drug	linagliptin/metformin(low dose)

Primary outcome

Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72)
Time frame: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.
Maximum Measured Concentration (Cmax) of Linagliptin.
Time frame: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.
Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval 0 to the Last Quantifiable Concentration (AUC0-tz)
Time frame: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.
Maximum Measured Concentration (Cmax) of Metformin
Time frame: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

3 secondary outcomes

Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) for Linagliptin
Time frame: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.
AUC(0-infinity) for Metformin
Time frame: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.
AUC0-tz for Linagliptin
Time frame: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.

Results and safety

Results posted to the registry on 6 Aug 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lina 2.5mg, Metformin 850mg	24	23
Lina 2.5mg, Metformin 500mg	24	24

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

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

Measure	Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet n = 23	Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets n = 24	Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet n = 24	Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets n = 24
Value	248 (14.5)	251 (15.3)	266 (22.1)	264 (23.8)

Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet vs Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets: adjusted gMean ratio: 99.5 (90% CI 94.7 to 104.5), ANOVA
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet vs Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets: adjusted gMean ratio: 100.8 (90% CI 95.1 to 106.8), ANOVA

Population analysed: Treated Set.

Primary outcome: Maximum Measured Concentration (Cmax) of Linagliptin.

Measure	Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet n = 23	Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets n = 24	Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet n = 24	Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets n = 24
Value	6.90 (23.1)	6.81 (18.2)	7.54 (35.4)	6.77 (25.9)

Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet vs Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets: adjusted gMean ratio: 101.9 (90% CI 95.4 to 109.0), ANOVA
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet vs Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets: adjusted gMean ratio: 111.4 (90% CI 100.4 to 123.5), ANOVA

Population analysed: Treated Set.

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

Measure	Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet n = 23	Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets n = 24	Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet n = 24	Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets n = 24
Value	11700 (27.9)	12100 (23.2)	8240 (20.8)	8010 (21.3)

Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet vs Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets: adjusted gMean ratio: 97.0 (90% CI 90.6 to 103.8), ANOVA
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet vs Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets: adjusteg gMean ratio: 103.0 (90% CI 96.2 to 110.1), ANOVA

Primary outcome: Maximum Measured Concentration (Cmax) of Metformin

Measure	Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet n = 23	Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets n = 24	Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet n = 24	Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets n = 24
Value	1680 (34.8)	1780 (26.0)	1220 (29.1)	1190 (27.2)

Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet vs Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets: adjusted gMean ratio: 94.6 (90% CI 85.4 to 104.8), ANOVA
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet vs Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets: adjusted gMean ratio: 102.5 (90% CI 92.2 to 113.9), ANOVA

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: First treatment with study drug until End-of-Study (which was 7 to 14 days after study drug treatment in Visit 3), i.e. 7 weeks plus 4 to 11 days after first treatment with study drug. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Linagliptin 2.5 mg, Metformin 850 mg as FDC Tablet	0 of 23 (0%)	0 of 23 (0%)	Not reported
Linagliptin 2.5 mg, Metformin 850 mg as Single Tablets	0 of 24 (0%)	2 of 24 (8.3%)	Not reported
Linagliptin 2.5 mg, Metformin 500 mg as FDC Tablet	0 of 24 (0%)	0 of 24 (0%)	Not reported
Linagliptin 2.5 mg, Metformin 500 mg as Single Tablets	0 of 24 (0%)	2 of 24 (8.3%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2013.
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 linagliptin/metformin(high dose) and Linagliptin/metformin(low dose) in people with Healthy, run by Boehringer Ingelheim at 1 site in China.

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 6 Aug 2013. 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 China. 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 6 Aug 2013). 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 0 to 72 Hours (AUC0-72) (time frame: 1 hour (h) prior to drug administration, 20 minutes (min), 40 min, 1 h, 1 h 30 min, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 34 h, 48 h and 72 h thereafter.). 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 NCT01540487.

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 6 Aug 2013.