Healthy
Conditions
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).
Interventions
DRUGLinagliptin/Metformin (standard batch)
Fixed dose combination tablet
DRUGLinagliptin/Metformin (side batch)
Fixed dose combination tablet
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
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: 17. Positive pregnancy test, pregnancy or planning to become pregnant 1 month before study or within 2 months after study completion 18. 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). 19. Lactation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Metformin: Cmax | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 | Geometric Mean of Cmax of Metformin |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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. |
| Metformin: Tmax | Day 1 to 35 for period 1, and Day 36 to 70 for period 2 | Median of tmax of metformin |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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. |
| 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 |
| 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 |
Countries
Germany
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Treatment with standard batch and side batch | 40 |
| Total | 40 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 36.8 Years STANDARD_DEVIATION 6.8 |
| Body mass index | 23.74 kg/m^2 STANDARD_DEVIATION 2.74 |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 40 | 11 / 40 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 |
Outcome results
Primary
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
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72) | 179 nmol*hr/L | Geometric Coefficient of Variation 21.6 |
| Side Batch | Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval 0 to 72 Hours (AUC0-72) | 179 nmol*hr/L | Geometric Coefficient of Variation 20.5 |
Comparison: Standard batch vs. Side batch90% CI: [96.1, 104.2]ANOVA
Primary
Linagliptin: Maximum Measured Concentration (Cmax)
Geometric mean of Cmax of Linagliptin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Linagliptin: Maximum Measured Concentration (Cmax) | 5.36 nmol/L | Geometric Coefficient of Variation 20.3 |
| Side Batch | Linagliptin: Maximum Measured Concentration (Cmax) | 5.39 nmol/L | Geometric Coefficient of Variation 20.3 |
Comparison: Standard batch vs. Side batch90% CI: [94.2, 105]ANOVA
Primary
Metformin: AUC0-tz
Geometric Mean of AUC0-tz of Metformin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Metformin: AUC0-tz | 12100 ng*hr/mL | Geometric Coefficient of Variation 21.4 |
| Side Batch | Metformin: AUC0-tz | 12100 ng*hr/mL | Geometric Coefficient of Variation 19.4 |
90% CI: [95.7, 105.4]ANOVA
Primary
Metformin: Cmax
Geometric Mean of Cmax of Metformin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Metformin: Cmax | 1790 ng/mL | Geometric Coefficient of Variation 23 |
| Side Batch | Metformin: Cmax | 1820 ng/mL | Geometric Coefficient of Variation 25.5 |
Comparison: Standard batch vs. Side batch90% CI: [92.5, 103.7]ANOVA
Secondary
Assessment of Tolerability by the Investigator
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
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Batch | Assessment of Tolerability by the Investigator | Good | 39 Participants |
| Standard Batch | Assessment of Tolerability by the Investigator | Not satisfactory | 1 Participants |
| Side Batch | Assessment of Tolerability by the Investigator | Not satisfactory | 0 Participants |
| Side Batch | Assessment of Tolerability by the Investigator | Good | 40 Participants |
Secondary
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
Time frame: Day 1 to 4 for period 1, and day 36 to 39 for period 2
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Batch | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | Physical examination abnormalities | 0 Participants |
| Standard Batch | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | Vital sign abnormalities | 0 Participants |
| Standard Batch | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | ECG abnormalities | 0 Participants |
| Standard Batch | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | Laboratory finding abnormalities | 0 Participants |
| Side Batch | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | Laboratory finding abnormalities | 0 Participants |
| Side Batch | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | Physical examination abnormalities | 0 Participants |
| Side Batch | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | ECG abnormalities | 0 Participants |
| Side Batch | Electrocardiogram (ECG), Vital Signs, Physical Finding or Laboratory Finding Abnormalities | Vital sign abnormalities | 0 Participants |
Secondary
Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F)
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
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F) | 330 mL/min | Geometric Coefficient of Variation 25.4 |
| Side Batch | Linagliptin: Apparent Clearance of the Analyte in Plasma After Extravascular Administration (CL/F) | 330 mL/min | Geometric Coefficient of Variation 23.6 |
Secondary
Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F)
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
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F) | 1300 Liter | Geometric Coefficient of Variation 22.8 |
| Side Batch | Linagliptin: Apparent Volume of Distribution During the Terminal Phase Following an Extravascular Dose (Vz/F) | 1300 Liter | Geometric Coefficient of Variation 24.6 |
Secondary
Linagliptin: AUC0-infinity
Geometric mean of AUC0-infinity of Linagliptin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Linagliptin: AUC0-infinity | 267 nmol*hr/L | Geometric Coefficient of Variation 25.4 |
| Side Batch | Linagliptin: AUC0-infinity | 267 nmol*hr/L | Geometric Coefficient of Variation 23.6 |
Comparison: Standard batch vs. Side batch90% CI: [94.7, 105.8]ANOVA
Secondary
Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
Geometric mean of the MRTpo of linagliptin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration) | 64.6 hr | Geometric Coefficient of Variation 15.7 |
| Side Batch | Linagliptin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration) | 64.5 hr | Geometric Coefficient of Variation 19.5 |
Secondary
Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation
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
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation | 32.6 percentage | Geometric Coefficient of Variation 17.5 |
| Side Batch | Linagliptin: Percentage of AUCtz-∞ Obtained by Extrapolation | 32.1 percentage | Geometric Coefficient of Variation 20.3 |
Secondary
Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax)
Median of the t\_max of linagliptin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Batch | Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax) | 3.00 hr |
| Side Batch | Linagliptin: Time to Maximum Measured Concentration of the Analyte in Plasma (Tmax) | 3.00 hr |
Secondary
Linagliptin: λz (Terminal Elimination Rate Constant in Plasma)
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
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Linagliptin: λz (Terminal Elimination Rate Constant in Plasma) | 0.0153 1/hr | Geometric Coefficient of Variation 17.1 |
| Side Batch | Linagliptin: λz (Terminal Elimination Rate Constant in Plasma) | 0.0152 1/hr | Geometric Coefficient of Variation 21.6 |
Secondary
Metformin: AUC0-infinity
Geometric Mean of AUC0-infinity of Metformin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Metformin: AUC0-infinity | 12400 ng*h/mL | Geometric Coefficient of Variation 21.2 |
| Side Batch | Metformin: AUC0-infinity | 12300 ng*h/mL | Geometric Coefficient of Variation 19.9 |
Comparison: Standard batch vs. Side batch90% CI: [95.7, 105.2]ANOVA
Secondary
Metformin: CL/F
Geometric mean of CL/F of metformin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Metformin: CL/F | 1350 mL/min | Geometric Coefficient of Variation 21.2 |
| Side Batch | Metformin: CL/F | 1350 mL/min | Geometric Coefficient of Variation 19.9 |
Secondary
Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration)
Geometric mean of MRTpo of metformin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration) | 8.27 hr | Geometric Coefficient of Variation 31.1 |
| Side Batch | Metformin: MRTpo (Mean Residence Time of the Analyte in the Body After Peroral Administration) | 8.23 hr | Geometric Coefficient of Variation 36.9 |
Secondary
Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation
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
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation | 1.51 percentage | Geometric Coefficient of Variation 87.4 |
| Side Batch | Metformin: Percentage of AUCtz-∞ Obtained by Extrapolation | 1.52 percentage | Geometric Coefficient of Variation 97 |
Secondary
Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma)
Geometric mean of t1/2 of metformin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma) | 14.1 hr | Geometric Coefficient of Variation 71 |
| Side Batch | Metformin: t1/2 (Terminal Half-life of the Analyte in Plasma) | 13.5 hr | Geometric Coefficient of Variation 84.3 |
Secondary
Metformin: Tmax
Median of tmax of metformin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Standard Batch | Metformin: Tmax | 1.99 hr |
| Side Batch | Metformin: Tmax | 2.00 hr |
Secondary
Metformin: Vz/F
Geometric mean of Vz/F of metformin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Metformin: Vz/F | 1640 Liter | Geometric Coefficient of Variation 74.3 |
| Side Batch | Metformin: Vz/F | 1580 Liter | Geometric Coefficient of Variation 82.4 |
Secondary
Metformin: λz (Terminal Elimination Rate Constant in Plasma)
Geometric mean of λz of metformin
Time frame: Day 1 to 35 for period 1, and Day 36 to 70 for period 2
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | Metformin: λz (Terminal Elimination Rate Constant in Plasma) | 0.0493 1/hr | Geometric Coefficient of Variation 71 |
| Side Batch | Metformin: λz (Terminal Elimination Rate Constant in Plasma) | 0.0514 1/hr | Geometric Coefficient of Variation 84.3 |
Secondary
Participants Who Discontinued the Trial Because of an Adverse Event
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
Population: Treated Set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Batch | Participants Who Discontinued the Trial Because of an Adverse Event | 0 Participants |
| Side Batch | Participants Who Discontinued the Trial Because of an Adverse Event | 0 Participants |
Secondary
Participants With Treatment Emergent Adverse Events
Number of patients with treatment emergent AEs
Time frame: Day 1 to 4 for period 1, and day 36 to 39 for period 2
Population: Treated Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Standard Batch | Participants With Treatment Emergent Adverse Events | Headache | 6 Participants |
| Standard Batch | Participants With Treatment Emergent Adverse Events | Nausea | 0 Participants |
| Standard Batch | Participants With Treatment Emergent Adverse Events | Vomiting | 2 Participants |
| Standard Batch | Participants With Treatment Emergent Adverse Events | Fatigue | 1 Participants |
| Side Batch | Participants With Treatment Emergent Adverse Events | Fatigue | 0 Participants |
| Side Batch | Participants With Treatment Emergent Adverse Events | Headache | 9 Participants |
| Side Batch | Participants With Treatment Emergent Adverse Events | Vomiting | 1 Participants |
| Side Batch | Participants With Treatment Emergent Adverse Events | Nausea | 1 Participants |
Secondary
t1/2 (Terminal Half-life of the Analyte in Plasma)
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
Population: Treated Set
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Standard Batch | t1/2 (Terminal Half-life of the Analyte in Plasma) | 45.4 hr | Geometric Coefficient of Variation 17.1 |
| Side Batch | t1/2 (Terminal Half-life of the Analyte in Plasma) | 45.6 hr | Geometric Coefficient of Variation 21.6 |