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This Study Tests Whether Taking the Medicines Empagliflozin, Linagliptin, and Metformin Together in 1 Pill is the Same as Taking Them in Separate Pills. The Study is Done in Healthy Men and Women and Measures the Amount of Each Medicine in the Blood

Phase 1
Completed
Conditions
Healthy
Interventions
Drug: Empagliflozin/linagliptin/metformin HCl
Registration Number
NCT03259490
Lead Sponsor
Boehringer Ingelheim
Brief Summary

To establish the bioequivalence of one fixed dose combination (FDC) tablet of empagliflozin/linagliptin/metformin extended release (XR) versus the free combination of empagliflozin tablet, linagliptin tablet, and metformin XR tablets administered as a single dose under fed conditions

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria
  • Healthy male or female subjects according to the assessment of the investigator, based on a complete medical history including a physical examination, vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
  • Age of 18 to 55 years (incl.)
  • BMI of 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 local legislation
  • Female subjects of childbearing potential willing to use adequate contraception.
  • Further inclusion criteria apply
Exclusion Criteria
  • Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR), or Electrocardiogram (ECG)) is deviating from normal and judged as clinically relevant by the investigator
  • Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 beats per minute (BPM)
  • Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
  • Any evidence of a concomitant disease judged as clinically relevant by the investigator
  • Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders
  • Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
  • Further exclusion criteria apply

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Reference TreatmentMetformin HClSingle tablets of empagliflozin + linagliptin + metformin XR
Test TreatmentEmpagliflozin/linagliptin/metformin HClHigh dose empagliflozin/linagliptin/metformin XR fixed dose combination tablet
Reference TreatmentEmpagliflozinSingle tablets of empagliflozin + linagliptin + metformin XR
Reference TreatmentLinagliptinSingle tablets of empagliflozin + linagliptin + metformin XR
Primary Outcome Measures
NameTimeMethod
Maximum Measured Concentration of the Empagliflozin in Plasma (Cmax)Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose

Maximum measured concentration of the empagliflozin in plasma (Cmax)

Cmax for Metformin in PlasmaPharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose

Cmax for metformin in plasma.

Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz) for EmpagliflozinPharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) for empagliflozin.

Plasma concentrations and/or parameters of a subject were to be considered as non-evaluable,if for example:

* The subject experienced emesis that occurred at or before 2 times median tmax of the respective treatment (median tmax was to be determined excluding the subjects experiencing emesis)

* A predose concentration was \>5% Cmax value of that subject

* Missing samples/concentration data at important phases of pharmacokinetic (PK) disposition curve.

Pharmacokinetic parameter set (PKS): This subject set included all subjects in the treated set (TS) who provided at least one primary or secondary PK parameter that was not excluded according to the description above. Thus, a subject was to be included in the PKS even if he/she contributed only one PK parameter value for one period to the statistical assessment.

AUC0-tz for Metformin.Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose

AUC0-tz for metformin.

Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72) for LinagliptinPharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose

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

Cmax for Linagliptin in PlasmaPharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose

Cmax for linagliptin in plasma.

Secondary Outcome Measures
NameTimeMethod
AUC(0-∞) for MetforminPharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose

AUC(0-∞) for Metformin

AUC(0-∞) for LinagliptinPharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose

AUC(0-∞) for Linagliptin

Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 Extrapolated to Infinity) for Empagliflozin (AUC(0-∞)Pharmacokinetic samples were collected at 1:30 hours: minutes pre dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 7:00, 8:00, 10:00, 12:00, 24:00, 34:00, 48:00 and 72:00 hours:minutes post dose

Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) for Empagliflozin (AUC(0-∞)

Trial Locations

Locations (1)

Humanpharmakologisches Zentrum Biberach

🇩🇪

Biberach, Germany

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