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Empa/Lina FDC Food Effect Study (Japan)

Investigation of the Effect of Food on the Bioavailability of Empagliflozin / Linagliptin Fixed Dose Combination Tablet in an Open, Randomised, Single Dose, Two Way Cross-over Study in Healthy Japanese Male Subjects

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02815644
Enrollment
22
Registered
2016-06-28
Start date
2016-07-15
Completion date
2016-10-05
Last updated
2018-08-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Brief summary

The trial will be performed as an open-label, randomised, single-dose, two-sequence crossover design for the assessment of effect of food on bioavailability of empagliflozin / linagliptin fixed dose combination (FDC) tablet.

Interventions

DRUGempagliflozin/linagliptin FDC

empagliflozin/linagliptin fixed-dose combination (FDC) film-coated tablet

Sponsors

Boehringer Ingelheim
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes

Inclusion criteria

* Healthy male subjects age \>=20 and \<=45 years; body weight: \>=50 kg and \<=80 kg; body mass index: \>=18.0 and \<=25.0 kg/m2 * Without any clinically significant findings and complications on the basis of a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR), body temperature) * Signed and dated written informed consent prior to admission to the trial in accordance with the Good Clinical Practice (GCP) and the local legislation

Exclusion criteria

* Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram) deviating from normal and of clinical relevance * Further

Design outcomes

Primary

MeasureTime frameDescription
Cmax for Linagliptin2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.Maximum measured concentration of the analyte in plasma (Cmax) for linagliptin
Cmax for Empagliflozin2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.Maximum measured concentration of the analyte in plasma (Cmax) for empagliflozin
AUC 0-tz for Linagliptin2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration (AUC 0-tz) for linagliptin
AUC 0-tz for Empagliflozin2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration (AUC 0-tz) for empagliflozin

Secondary

MeasureTime frameDescription
AUC0-infinity for Empagliflozin2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) for empagliflozin.
AUC0-72 for Linagliptin2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours (AUC0-72) for linagliptin
AUC0-infinity for Linagliptin2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) for linagliptin

Countries

Japan

Participant flow

Pre-assignment details

This is a Open-label, randomised, single-dose, two-sequence, crossover design

Participants by arm

ArmCount
Empagliflozin 25 mg/ Linagliptin 5 mg (Sequence 1: Fed-Fasted)
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film coated tablet with 150 mL water after a standard Japanese breakfast in period 1 and after an overnight fast in period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
11
Empagliflozin 25 mg/ Linagliptin 5 mg (Sequence 2: Fasted-Fed)
Patient were orally administered Empagliflozin 25 mg/ linagliptin 5 mg fixed-dose combination (FDC) film-coated tablet with 150 mL water after an overnight fast in period 1 and after a standard Japanese breakfast in period 2. Single-dose in each treatment period separated by wash-out period of at least 35 days
11
Total22

Baseline characteristics

CharacteristicEmpagliflozin 25 mg/ Linagliptin 5 mg (Sequence 1: Fed-Fasted)Empagliflozin 25 mg/ Linagliptin 5 mg (Sequence 2: Fasted-Fed)Total
Age, Continuous29.00 Years
STANDARD_DEVIATION 8.83
33.73 Years
STANDARD_DEVIATION 9.55
31.36 Years
STANDARD_DEVIATION 9.3
Sex: Female, Male
Female
0 Participants0 Participants0 Participants
Sex: Female, Male
Male
11 Participants11 Participants22 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 220 / 22
serious
Total, serious adverse events
0 / 220 / 22

Outcome results

Primary

AUC 0-tz for Empagliflozin

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration (AUC 0-tz) for empagliflozin

Time frame: 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.

Population: PKS

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted)AUC 0-tz for Empagliflozin7210 nmol∙h/LGeometric Coefficient of Variation 19.1
Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)AUC 0-tz for Empagliflozin6200 nmol∙h/LGeometric Coefficient of Variation 20.6
Comparison: Relative bioavailability of empagliflozin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: sequence, subjects within sequences, period, and treatment (i.e., feeding status). The effect subjects within sequences was considered as random, whereas the other effects were considered as fixed.90% CI: [83.38, 88.68]
Primary

AUC 0-tz for Linagliptin

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration (AUC 0-tz) for linagliptin

Time frame: 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.

Population: PKS

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted)AUC 0-tz for Linagliptin348 nmol∙h/LGeometric Coefficient of Variation 15.4
Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)AUC 0-tz for Linagliptin286 nmol∙h/LGeometric Coefficient of Variation 20.5
Comparison: Relative bioavailability of linagliptin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: sequence, subjects within sequences, period, and treatment (i.e., feeding status). The effect subjects within sequences was considered as random, whereas the other effects were considered as fixed.90% CI: [78.38, 86.18]
Primary

Cmax for Empagliflozin

Maximum measured concentration of the analyte in plasma (Cmax) for empagliflozin

Time frame: 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.

Population: PKS

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted)Cmax for Empagliflozin1010 nmol/LGeometric Coefficient of Variation 27.1
Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)Cmax for Empagliflozin756 nmol/LGeometric Coefficient of Variation 27.3
Comparison: Relative bioavailability of empagliflozin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: sequence, subjects within sequences, period, and treatment (i.e., feeding status). The effect subjects within sequences was considered as random, whereas the other effects were considered as fixed.90% CI: [66.27, 84.64]
Primary

Cmax for Linagliptin

Maximum measured concentration of the analyte in plasma (Cmax) for linagliptin

Time frame: 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.

Population: Pharmacokinetic Set (PKS): The PKS included all 22 randomised subjects who were documented to have taken at least 1 dose of trial medication under fed or fasted condition without having protocol deviation relevant to the evaluation of relative bioavailability and without experiencing emesis at or before 2 times median tmax.

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted)Cmax for Linagliptin15.1 nmol/LGeometric Coefficient of Variation 50.6
Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)Cmax for Linagliptin8.43 nmol/LGeometric Coefficient of Variation 30.3
Comparison: Relative bioavailability of linagliptin after food intake compared to while in the fasting state was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: sequence, subjects within sequences, period, and treatment (i.e., feeding status). The effect subjects within sequences was considered as random, whereas the other effects were considered as fixed.90% CI: [48.22, 64.33]
Secondary

AUC0-72 for Linagliptin

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 72 hours (AUC0-72) for linagliptin

Time frame: 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.

Population: PKS

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted)AUC0-72 for Linagliptin348 nmol∙h/LGeometric Coefficient of Variation 15.4
Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)AUC0-72 for Linagliptin286 nmol∙h/LGeometric Coefficient of Variation 20.5
Comparison: Relative bioavailability of linagliptin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: sequence, subjects within sequences, period, and treatment (i.e., feeding status). The effect subjects within sequences was considered as random, whereas the other effects were considered as fixed.90% CI: [78.38, 86.18]
Secondary

AUC0-infinity for Empagliflozin

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-infinity) for empagliflozin.

Time frame: 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.

Population: PKS

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted)AUC0-infinity for Empagliflozin7270 nmol∙h/LGeometric Coefficient of Variation 19.1
Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)AUC0-infinity for Empagliflozin6280 nmol∙h/LGeometric Coefficient of Variation 20.4
Comparison: Relative bioavailability of empagliflozin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: sequence, subjects within sequences, period, and treatment (i.e., feeding status). The effect subjects within sequences was considered as random, whereas the other effects were considered as fixed.90% CI: [83.61, 89.13]
Secondary

AUC0-infinity for Linagliptin

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: 2 hours (h) before the administration in first subject and 0:20 h, 0:40h, 1:00h, 1:30h, 2:00h, 2:30h, 3:00h, 4:00h, 6:00h, 8:00h, 10:00h, 12:00h, 24:00h, 34:00h, 48:00h, 72:00h after drug administration.

Population: PKS

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Empagliflozin 25 mg/ Linagliptin 5 mg (Reference;Fasted)AUC0-infinity for Linagliptin597 nmol∙h/LGeometric Coefficient of Variation 20.6
Empagliflozin 25 mg/ Linagliptin 5 mg (Test;Fed)AUC0-infinity for Linagliptin526 nmol∙h/LGeometric Coefficient of Variation 33.4
Comparison: Relative bioavailability of linagliptin was assessed using an ANOVA on the basis of the log transformed PK parameters. This model for the evaluation of effect of food on bioavailability included the effects: sequence, subjects within sequences, period, and treatment (i.e., feeding status). The effect subjects within sequences was considered as random, whereas the other effects were considered as fixed.90% CI: [80.89, 96.03]

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026