HealthyPhase 1NCT01216397

Relative Bioavailability of Two Different Batches of a Linagliptin / Metformin Combination Tablet in Healthy Volunteers

A Phase 1 study testing Linagliptin/Metformin (standard batch) and Linagliptin/Metformin (side batch) 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 objective of the current study is to investigate the relative bioavailability of two different batches of a 2.5 mg linagliptin / 1000 mg metformin fixed dose combination tablet (FDC). Read more about this study

Who is it for?: Ages 21 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Linagliptin/Metformin (standard batch) and Linagliptin/Metformin (side batch)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 1 siteGermany
Study dates: Sep 2010to Dec 2010
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 21 to 50 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Healthy males and females according to the following criteria: Based upon a complete medical history, including physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
Age 21 to 50 years (incl.)
Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.)
Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

Who cannot join

Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
Any evidence of a clinically relevant concomitant disease
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Surgery of the gastrointestinal tract (except appendectomy)
Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
History of relevant orthostatic hypotension, fainting spells or blackouts

Show all 20Show fewer

Chronic or relevant acute infections
History of relevant allergy or hypersensitivity (including allergy to drug or its excipients)
Intake of drugs within one month or less than 10 half-lives of the respective drug prior to first study drug administration
Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
Smoker (more than 10 cigarettes or 3 cigars 3 pipes daily)
Alcohol abuse (average consumption of more than 20 g/day in females and 30 g/day in males)
Drug abuse
Blood donation (more than 100 mL within four weeks prior to day 1 of visit 2)
Any laboratory value outside the reference range that is of clinical relevance
Inability to comply with dietary regimen of trial site
For female subjects of childbearing potential only:
Positive pregnancy test, pregnancy or planning to become pregnant 1 month before study or within 2 months after study completion
No adequate contraception 1 month before study and until 2 month after study completion, e.g. not any of the following: implants, injectables, combined hormonal contraceptives, hormonal IUD (intrauterine device), sexual abstinence for at least 1 month prior to first study drug administration, vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who do not have a vasectomised partner, are not sexually abstinent or surgically sterile will be asked to use an additional barrier method (e.g. condom).
Lactation

Trial locations and contacts

1 site in 1 country.

Germany1 site

1288.6.1 Boehringer Ingelheim Investigational Site
Ingelheim

Other trials in Germany

About this study

Official title: Relative Bioavailability of Two Different Batches of a 2.5 mg Linagliptin / 1000 mg Metformin Fixed Dose Combination Tablet (FDC) in Healthy Male and Female Volunteers (an Open-label, Randomised, Single Dose, Two-way Crossover, Phase I Trial)

The objective of the current study is to investigate the relative bioavailability of two different batches of a 2.5 mg linagliptin / 1000 mg metformin fixed dose combination tablet (FDC).

Conditions: Healthy
Being tested: Linagliptin/Metformin (standard batch), Linagliptin/Metformin (side batch)

What participants receive

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

Linagliptin/Metformin (standard batch)Drug
Fixed dose combination tablet
Linagliptin/Metformin (side batch)Drug
Fixed dose combination tablet

Study groups in NCT01216397
Study group	Role	What they receive
Linagliptin/Metformin (standard batch)	Experimental	Fixed dose combination tablet Receives: Drug: Linagliptin/Metformin (standard batch)
Linagliptin/Metformin (side batch)	Experimental	Fixed dose combination tablet Receives: Drug: Linagliptin/Metformin (side batch)

What is being measured

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

Linagliptin: Maximum Measured Concentration (Cmax)
Geometric mean of Cmax of Linagliptin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72)
Geometric mean of AUC0-72 of Linagliptin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: Cmax
Geometric Mean of Cmax of Metformin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: AUC0-tz
Geometric Mean of AUC0-tz of Metformin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Secondary outcomes (20)

Linagliptin: AUC0-infinity
Geometric mean of AUC0-infinity of Linagliptin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation
Geometric Mean of percentage of AUCtz-∞ of linagliptin, where percentage is the unit of measurement.
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax)
Median of the t_max of linagliptin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: λz (Terminal Elimination Rate Constant in Plasma)
Geometric mean of the λ_z of linagliptin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
t1/2 (Terminal Half-life of the Analyte in Plasma)
Geometric mean of the t1/2 of linagliptin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
Geometric mean of the MRTpo of linagliptin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F)
Geometric mean of the CL/F of linagliptin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F)
Geometric mean of the Vz/F of linagliptin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: AUC0-infinity
Geometric Mean of AUC0-infinity of Metformin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation
Geometric Mean of the percentage of AUCtz-infinity of Metformin, where percentage is the unit of measurement.
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: Tmax
Median of tmax of metformin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: λz (Terminal Elimination Rate Constant in Plasma)
Geometric mean of λz of metformin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma)
Geometric mean of t1/2 of metformin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
Geometric mean of MRTpo of metformin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: CL/F
Geometric mean of CL/F of metformin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: Vz/F
Geometric mean of Vz/F of metformin
Measured: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities
12-lead-Electrocardiogram (ECG), vital sign (blood pressure and pulse rate), physical finding and laboratory abnormalities
Measured: Day 1 to 4 for period 1, and day 36 to 39 for period 2
Participants With Treatment Emergent Adverse Events
Number of patients with treatment emergent AEs
Measured: Day 1 to 4 for period 1, and day 36 to 39 for period 2
Participants Who Discontinued the Trial Because of an Adverse Event
Number of participants who discontinued the trial because of an adverse event
Measured: Day 1 to 4 for period 1, and day 36 to 39 for period 2
Assessment of Tolerability by the Investigator
Qualitative variable assessing the tolerability by the investigator
Measured: Day 1 to 4 for period 1, and day 36 to 39 for period 2

Timeline

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

Sep 2010Dec 2010

First posted7 Oct 2010 (estimated)
Study startSep 2010
Primary completionDec 2010

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: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01216397
Sponsor's protocol ID: 1288.6
Other IDs: 2010-019291-75
Status last verified: Feb 2014
First submitted: 4 Oct 2010
Last updated: 27 Jun 2014
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 27 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Relative Bioavailability of Two Different Batches of a 2.5 mg Linagliptin / 1000 mg Metformin Fixed Dose Combination Tablet (FDC) in Healthy Male and Female Volunteers (an Open-label, Randomised, Single Dose, Two-way Crossover, Phase I Trial)
ClinicalTrials.gov ID: NCT01216397
Acronym / sponsor ID: 1288.6
Conditions: Healthy
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Sep 2010
Primary completion: Dec 2010 (actual)
First posted: 7 Oct 2010 (estimated)
Results: Posted 25 Apr 2012

Clinical summary

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

The objective of the current study is to investigate the relative bioavailability of two different batches of a 2.5 mg linagliptin / 1000 mg metformin fixed dose combination tablet (FDC).

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Linagliptin/Metformin (standard batch)	Experimental	Drug: Linagliptin/Metformin (standard batch)Fixed dose combination tablet
Linagliptin/Metformin (side batch)	Experimental	Drug: Linagliptin/Metformin (side batch)Fixed dose combination tablet

Who may qualify

Ages: 21 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Healthy males and females according to the following criteria: Based upon a complete medical history, including physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
Age 21 to 50 years (incl.)
Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.)
Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

Key exclusion criteria (20 listed)

Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance
Any evidence of a clinically relevant concomitant disease
Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
Surgery of the gastrointestinal tract (except appendectomy)
Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders

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 (standard batch)Fixed dose combination tablet	Drug	Linagliptin/Metformin (standard batch)
Linagliptin/Metformin (side batch)Fixed dose combination tablet	Drug	Linagliptin/Metformin (side batch)

Primary outcome

Linagliptin: Maximum Measured Concentration (Cmax)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Geometric mean of Cmax of Linagliptin
Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Geometric mean of AUC0-72 of Linagliptin
Metformin: Cmax
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Geometric Mean of Cmax of Metformin
Metformin: AUC0-tz
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Geometric Mean of AUC0-tz of Metformin

20 secondary outcomes

Linagliptin: AUC0-infinity
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: λz (Terminal Elimination Rate Constant in Plasma)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
t1/2 (Terminal Half-life of the Analyte in Plasma)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: AUC0-infinity
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: Tmax
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: λz (Terminal Elimination Rate Constant in Plasma)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: CL/F
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Metformin: Vz/F
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities
Time frame: Day 1 to 4 for period 1, and day 36 to 39 for period 2
Participants With Treatment Emergent Adverse Events
Time frame: Day 1 to 4 for period 1, and day 36 to 39 for period 2
Participants Who Discontinued the Trial Because of an Adverse Event
Time frame: Day 1 to 4 for period 1, and day 36 to 39 for period 2
Assessment of Tolerability by the Investigator
Time frame: Day 1 to 4 for period 1, and day 36 to 39 for period 2

Results and safety

Results posted to the registry on 25 Apr 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Standard Batch Then Side Batch	20	20
Side Batch Then Standard Batch	20	20

Primary outcome: Linagliptin: Maximum Measured Concentration (Cmax)

Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2. Geometric mean (Geometric Coefficient of Variation). Unit: nmol/L

Measure	Standard Batch n = 40	Side Batch n = 40
Value	5.36 (20.3)	5.39 (20.3)

Standard Batch vs Side Batch: adjusted gMean ratio: 99.4 (90% CI 94.2 to 105.0), ANOVA

Population analysed: Treated Set

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

Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2. Geometric mean (Geometric Coefficient of Variation). Unit: nmol*hr/L

Measure	Standard Batch n = 40	Side Batch n = 40
Value	179 (21.6)	179 (20.5)

Standard Batch vs Side Batch: adjusted gMean ratio: 100.1 (90% CI 96.1 to 104.2), ANOVA

Population analysed: Treated Set

Primary outcome: Metformin: Cmax

Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2. Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Standard Batch n = 40	Side Batch n = 40
Value	1790 (23.0)	1820 (25.5)

Standard Batch vs Side Batch: adjusted gMean ratio: 97.9 (90% CI 92.5 to 103.7), ANOVA

Population analysed: Treated Set

Primary outcome: Metformin: AUC0-tz

Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	Standard Batch n = 40	Side Batch n = 40
Value	12100 (21.4)	12100 (19.4)

Standard Batch vs Side Batch: adjusted gMean ratio: 100.4 (90% CI 95.7 to 105.4), ANOVA

Population analysed: Treated Set

20 secondary outcomes are reported in the full results.

Adverse events

Time frame: 4 days (period 1) + 4 days (treatment period 2). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Standard Batch	0 of 40 (0%)	7 of 40 (17.5%)	Not reported
Side Batch	0 of 40 (0%)	11 of 40 (27.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related InfoLink provided by the sponsor.
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 (standard batch) and Linagliptin/Metformin (side batch) 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 4 inclusion and 20 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 27 Jun 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 25 Apr 2012). 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: Maximum Measured Concentration (Cmax) (time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2). 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 NCT01216397.

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 27 Jun 2014.