Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Linagliptin Compared With the Free Combination of Empagliflozin Tablet and Linagliptin Tablet in Healthy Male and Female Subjects

Bioequivalence of a Fixed Dose Combination Tablet of Empagliflozin/Linagliptin Compared With the Free Combination of Empagliflozin Tablet and Linagliptin Tablet in Healthy Male and Female Subjects (an Open-label, Randomised, Single-dose, Crossover Study)

The primary objective of this trial is to investigate the bioequivalence of one fixed dose combination tablet of empagliflozin/linagliptin (Test, T) compared with the free combination of one empagliflozin tablet and one linagliptin tablet (Reference, R) administered as single dose under fasted conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Empagliflozin; Drug: Linagliptin

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Biberach, Germany, 88397
    • Humanpharmakologisches Zentrum Biberach

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Healthy male or female subjects according to the investigators assessment, 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.)
• Body Mass Index (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 GCP (Good Clinical Practice) and local legislation
• Male subjects, or female subjects who meet any of the following criteria starting from at least 30 days before the first administration of trial medication and until 30 days after trial completion:
• Use of adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives, intrauterine device
• Sexually abstinent
• A vasectomised sexual partner (vasectomy at least 1 year prior to enrolment)
• Surgically sterilised (including hysterectomy)
• Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of FSH (Follicle Stimulating Hormone) above 40 U/L and estradiol below 30 ng/L is confirmatory)

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 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
• Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and simple hernia repair)
• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin+Linagliptin FDC; One tablet fix dose combination (FDC)	Drug: Empagliflozin; Drug: Linagliptin
Active Comparator: Empagliflozin+Linagliptin single tablets	Drug: Empagliflozin; Drug: Linagliptin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-tz (Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point)	This outcome measure presents area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the last quantifiable data point. Time frame description: The time -1:00 hour (h) was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for AUC0-tz (area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the last quantifiable data point).	1:00 [hour (h): minute] before drug administration and 0:20h, 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, and 72:00h after drug administration.
AUC0-72 (Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours)	This outcome measure presents area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 to 72 hours. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for AUC0-72 (area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 to 72 hours).	1:00 [hour (h): minute] before drug administration and 0:20h, 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, and 72:00h after drug administration.
Cmax (Maximum Measured Concentration of Empagliflozin Analyte in Plasma)	This outcome measure presents maximum measured concentration of Empagliflozin analyte in plasma. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for Cmax (maximum measured concentration of Empagliflozin analyte in plasma).	1:00 [hour (h): minute] before drug administration and 0:20h, 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, and 72:00h after drug administration.
Cmax (Maximum Measured Concentration of Linagliptin Analyte in Plasma)	This outcome measure presents maximum measured concentration of Linagliptin analyte in plasma. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for Cmax (maximum measured concentration of Linagliptin analyte in plasma).	1:00 [hour (h): minute] before drug administration and 0:20h, 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, and 72:00h after drug administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC0-infinity (Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity)	This outcome measure presents area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 extrapolated to infinity. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for AUC0-infinity (area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 extrapolated to infinity).	1:00 [hour (h): minute] before drug administration and 0:20h, 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, and 72:00h after drug administration.
AUC0-infinity (Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity)	This outcome measure presents area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 extrapolated to infinity. Time frame description: The time -1:00h was approximate; the procedure was to be performed and completed within 2h before drug administration. PKS including participants with available data for (area under the concentration-time curve of Linagliptin in plasma over the time interval from 0 extrapolated to infinity).	1:00 [hour (h): minute] before drug administration and 0:20h, 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, and 72:00h after drug administration.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim
• Collaborators: Eli Lilly and Company

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2016
• Primary Completion (Actual): July 29, 2016
• Study Completion (Actual): August 3, 2016

Study Registration Dates

• First Submitted: April 29, 2016
• First Submitted That Met QC Criteria: April 29, 2016
• First Posted (Estimate): May 2, 2016

Study Record Updates

• Last Update Posted (Actual): November 22, 2017
• Last Update Submitted That Met QC Criteria: June 27, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Empagliflozin; Linagliptin
• Other Study ID Numbers: 1275.21; 2015-004234-98 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No