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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01216397
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2

Study Details

Study Description

Brief 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).

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Linagliptin/Metformin (standard batch); Drug: Linagliptin/Metformin (side batch)	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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)
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Linagliptin/Metformin (standard batch) Fixed dose combination tablet	Drug: Linagliptin/Metformin (standard batch); Fixed dose combination tablet
Experimental: Linagliptin/Metformin (side batch) Fixed dose combination tablet	Drug: Linagliptin/Metformin (side batch); Fixed dose combination tablet

Outcome Measures

Primary Outcome Measures

1. Linagliptin: Maximum Measured Concentration (Cmax) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric mean of Cmax of Linagliptin

2. Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric mean of AUC0-72 of Linagliptin

3. Metformin: Cmax [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric Mean of Cmax of Metformin

4. Metformin: AUC0-tz [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric Mean of AUC0-tz of Metformin

Secondary Outcome Measures

1. Linagliptin: AUC0-infinity [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric mean of AUC0-infinity of Linagliptin

2. Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric Mean of percentage of AUCtz-∞ of linagliptin, where percentage is the unit of measurement.

3. Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Median of the t_max of linagliptin

4. Linagliptin: λz (Terminal Elimination Rate Constant in Plasma) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric mean of the λ_z of linagliptin

5. t1/2 (Terminal Half-life of the Analyte in Plasma) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric mean of the t1/2 of linagliptin

6. Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric mean of the MRTpo of linagliptin

7. Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric mean of the CL/F of linagliptin

8. Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric mean of the Vz/F of linagliptin

9. Metformin: AUC0-infinity [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

   Geometric Mean of AUC0-infinity of Metformin

10. Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

    Geometric Mean of the percentage of AUCtz-infinity of Metformin, where percentage is the unit of measurement.

11. Metformin: Tmax [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

    Median of tmax of metformin

12. Metformin: λz (Terminal Elimination Rate Constant in Plasma) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

    Geometric mean of λz of metformin

13. Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

    Geometric mean of t1/2 of metformin

14. Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration) [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

    Geometric mean of MRTpo of metformin

15. Metformin: CL/F [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

    Geometric mean of CL/F of metformin

16. Metformin: Vz/F [Day 1 to 35 for period 1, and Day 36 to 70 for period 2]

    Geometric mean of Vz/F of metformin

17. Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities [Day 1 to 4 for period 1, and day 36 to 39 for period 2]

    12-lead-Electrocardiogram (ECG), vital sign (blood pressure and pulse rate), physical finding and laboratory abnormalities

18. Participants With Treatment Emergent Adverse Events [Day 1 to 4 for period 1, and day 36 to 39 for period 2]

    Number of patients with treatment emergent AEs

19. Participants Who Discontinued the Trial Because of an Adverse Event [Day 1 to 4 for period 1, and day 36 to 39 for period 2]

    Number of participants who discontinued the trial because of an adverse event

20. Assessment of Tolerability by the Investigator [Day 1 to 4 for period 1, and day 36 to 39 for period 2]

    Qualitative variable assessing the tolerability by the investigator

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

1. 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

2. Age 21 to 50 years (incl.)

3. Body Mass Index (BMI) 18.5 to 29.9 kg/m2 (incl.)

4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation

Exclusion criteria:

1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance

2. Any evidence of a clinically relevant concomitant disease

3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders

4. Surgery of the gastrointestinal tract (except appendectomy)

5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders

6. History of relevant orthostatic hypotension, fainting spells or blackouts

7. Chronic or relevant acute infections

8. History of relevant allergy or hypersensitivity (including allergy to drug or its excipients)

9. Intake of drugs within one month or less than 10 half-lives of the respective drug prior to first study drug administration

10. Participation in another trial with an investigational drug within 2 months prior to administration or during the trial

11. Smoker (more than 10 cigarettes or 3 cigars 3 pipes daily)

12. Alcohol abuse (average consumption of more than 20 g/day in females and 30 g/day in males)

13. Drug abuse

14. Blood donation (more than 100 mL within four weeks prior to day 1 of visit 2)

15. Any laboratory value outside the reference range that is of clinical relevance

16. Inability to comply with dietary regimen of trial site

For female subjects of childbearing potential only:

1. Positive pregnancy test, pregnancy or planning to become pregnant 1 month before study or within 2 months after study completion

2. 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).

3. Lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1288.6.1 Boehringer Ingelheim Investigational Site	Ingelheim		Germany

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT01216397
• Other Study ID Numbers: 1288.6; 2010-019291-75
• First Posted: Oct 7, 2010
• Last Update Posted: Jun 27, 2014
• Last Verified: Feb 1, 2014

• Additional relevant MeSH terms: Metformin; Linagliptin

Study Results

Participant Flow

Pre-assignment Detail	This was an open-label, single-dose, randomised, 2-way crossover trial. Subjects were equally randomised to one of two sequences, and in general terms, AB or BA. Hence, 20 subjects were in group AB and 20 in group BA. All 40 subjects received A and B. The numbers presented in the milestones are overall, which is consistent with the trial report.

Arm/Group Title	Standard Batch Then Side Batch	Side Batch Then Standard Batch
Arm/Group Description	Linagliptin/metformin FDC tablet from standard batch, then Linagliptin/metformin FDC tablet from side batch	Linagliptin/metformin FDC tablet from side batch, then Linagliptin/metformin FDC tablet from standard batch
Period Title: Period 1
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0
Period Title: Period 1
STARTED	20	20
COMPLETED	20	20
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	Treatment with standard batch and side batch
Overall Participants	40
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	36.8 (6.8)
Sex: Female, Male (Count of Participants)
Female	20 50%
Male	20 50%
Body mass index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	23.74 (2.74)

Outcome Measures

1. Primary Outcome

Title	Linagliptin: Maximum Measured Concentration (Cmax)
Description	Geometric mean of Cmax of Linagliptin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [nmol/L]	5.36 (20.3)	5.39 (20.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Batch, Side Batch
	Comments	Standard batch vs. Side batch
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	adjusted gMean ratio
	Estimated Value	99.4
	Confidence Interval	() 90%; 94.2 to 105.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72)
Description	Geometric mean of AUC0-72 of Linagliptin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [nmol*hr/L]	179 (21.6)	179 (20.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Batch, Side Batch
	Comments	Standard batch vs. Side batch
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	adjusted gMean ratio
	Estimated Value	100.1
	Confidence Interval	() 90%; 96.1 to 104.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Linagliptin: AUC0-infinity
Description	Geometric mean of AUC0-infinity of Linagliptin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [nmol*hr/L]	267 (25.4)	267 (23.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Batch, Side Batch
	Comments	Standard batch vs. Side batch
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	adjusted gMean ratio
	Estimated Value	100.1
	Confidence Interval	() 90%; 94.7 to 105.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation
Description	Geometric Mean of percentage of AUCtz-∞ of linagliptin, where percentage is the unit of measurement.
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [percentage]	32.6 (17.5)	32.1 (20.3)

5. Secondary Outcome

Title	Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax)
Description	Median of the t_max of linagliptin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Median (Full Range) [hr]	3.00	3.00

6. Secondary Outcome

Title	Linagliptin: λz (Terminal Elimination Rate Constant in Plasma)
Description	Geometric mean of the λ_z of linagliptin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [1/hr]	0.0153 (17.1)	0.0152 (21.6)

7. Secondary Outcome

Title	t1/2 (Terminal Half-life of the Analyte in Plasma)
Description	Geometric mean of the t1/2 of linagliptin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [hr]	45.4 (17.1)	45.6 (21.6)

8. Secondary Outcome

Title	Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
Description	Geometric mean of the MRTpo of linagliptin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [hr]	64.6 (15.7)	64.5 (19.5)

9. Secondary Outcome

Title	Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F)
Description	Geometric mean of the CL/F of linagliptin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [mL/min]	330 (25.4)	330 (23.6)

10. Secondary Outcome

Title	Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F)
Description	Geometric mean of the Vz/F of linagliptin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [Liter]	1300 (22.8)	1300 (24.6)

11. Primary Outcome

Title	Metformin: Cmax
Description	Geometric Mean of Cmax of Metformin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	1790 (23.0)	1820 (25.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Batch, Side Batch
	Comments	Standard batch vs. Side batch
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	adjusted gMean ratio
	Estimated Value	97.9
	Confidence Interval	() 90%; 92.5 to 103.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Primary Outcome

Title	Metformin: AUC0-tz
Description	Geometric Mean of AUC0-tz of Metformin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	12100 (21.4)	12100 (19.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Batch, Side Batch
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	adjusted gMean ratio
	Estimated Value	100.4
	Confidence Interval	() 90%; 95.7 to 105.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Metformin: AUC0-infinity
Description	Geometric Mean of AUC0-infinity of Metformin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	12400 (21.2)	12300 (19.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Standard Batch, Side Batch
	Comments	Standard batch vs. Side batch
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	adjusted gMean ratio
	Estimated Value	100.3
	Confidence Interval	() 90%; 95.7 to 105.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation
Description	Geometric Mean of the percentage of AUCtz-infinity of Metformin, where percentage is the unit of measurement.
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [percentage]	1.51 (87.4)	1.52 (97.0)

15. Secondary Outcome

Title	Metformin: Tmax
Description	Median of tmax of metformin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Median (Full Range) [hr]	1.99	2.00

16. Secondary Outcome

Title	Metformin: λz (Terminal Elimination Rate Constant in Plasma)
Description	Geometric mean of λz of metformin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [1/hr]	0.0493 (71.0)	0.0514 (84.3)

17. Secondary Outcome

Title	Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma)
Description	Geometric mean of t1/2 of metformin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [hr]	14.1 (71.0)	13.5 (84.3)

18. Secondary Outcome

Title	Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
Description	Geometric mean of MRTpo of metformin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [hr]	8.27 (31.1)	8.23 (36.9)

19. Secondary Outcome

Title	Metformin: CL/F
Description	Geometric mean of CL/F of metformin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [mL/min]	1350 (21.2)	1350 (19.9)

20. Secondary Outcome

Title	Metformin: Vz/F
Description	Geometric mean of Vz/F of metformin
Time Frame	Day 1 to 35 for period 1, and Day 36 to 70 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Geometric Mean (Geometric Coefficient of Variation) [Liter]	1640 (74.3)	1580 (82.4)

21. Secondary Outcome

Title	Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities
Description	12-lead-Electrocardiogram (ECG), vital sign (blood pressure and pulse rate), physical finding and laboratory abnormalities
Time Frame	Day 1 to 4 for period 1, and day 36 to 39 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Physical examination abnormalities	0 0%	0 NaN
Vital sign abnormalities	0 0%	0 NaN
ECG abnormalities	0 0%	0 NaN
Laboratory finding abnormalities	0 0%	0 NaN

22. Secondary Outcome

Title	Participants With Treatment Emergent Adverse Events
Description	Number of patients with treatment emergent AEs
Time Frame	Day 1 to 4 for period 1, and day 36 to 39 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Headache	6 15%	9 NaN
Nausea	0 0%	1 NaN
Vomiting	2 5%	1 NaN
Fatigue	1 2.5%	0 NaN

23. Secondary Outcome

Title	Participants Who Discontinued the Trial Because of an Adverse Event
Description	Number of 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

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Number [Participants]	0 0%	0 NaN

24. Secondary Outcome

Title	Assessment of Tolerability by the Investigator
Description	Qualitative variable assessing the tolerability by the investigator
Time Frame	Day 1 to 4 for period 1, and day 36 to 39 for period 2

Outcome Measure Data

Analysis Population Description

Treated Set

Arm/Group Title	Standard Batch	Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC	side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
Measure Participants	40	40
Good	39 97.5%	40 NaN
Not satisfactory	1 2.5%	0 NaN

Adverse Events

Time Frame	4 days (period 1) + 4 days (treatment period 2)
Adverse Event Reporting Description	Two identical treatment periods with an interval of at least 35 days between drug administrations.
Arm/Group Title	Standard Batch		Side Batch
Arm/Group Description	standard batch of a 2.5 mg linagliptin/ 1000mg metformin FDC		side batch of a 2.5 mg linagliptin/ 1000mg metformin FDC
All Cause Mortality
	Standard Batch		Side Batch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Standard Batch		Side Batch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Standard Batch		Side Batch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/40 (17.5%)		11/40 (27.5%)
Nervous system disorders
Headache	7/40 (17.5%)		11/40 (27.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Other - Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.