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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

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ClinicalTrials.gov Identifier: NCT02758171
Recruitment Status : Completed
First Posted : May 2, 2016
Results First Posted : November 22, 2017
Last Update Posted : November 22, 2017
Sponsor:
Collaborator:
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Empagliflozin Drug: Linagliptin Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : May 17, 2016
Actual Primary Completion Date : July 29, 2016
Actual Study Completion Date : August 3, 2016

Resource links provided by the National Library of Medicine


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



Primary Outcome Measures :
  1. AUC0-tz (Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point) [ Time Frame: 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. ]

    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).


  2. AUC0-72 (Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours) [ Time Frame: 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. ]

    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).


  3. Cmax (Maximum Measured Concentration of Empagliflozin Analyte in Plasma) [ Time Frame: 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. ]

    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).


  4. Cmax (Maximum Measured Concentration of Linagliptin Analyte in Plasma) [ Time Frame: 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. ]

    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).



Secondary Outcome Measures :
  1. AUC0-infinity (Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity) [ Time Frame: 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. ]

    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).


  2. AUC0-infinity (Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity) [ Time Frame: 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. ]

    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).




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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02758171


Locations
Germany
Humanpharmakologisches Zentrum Biberach
Biberach, Germany, 88397
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim

Additional Information:
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02758171     History of Changes
Other Study ID Numbers: 1275.21
2015-004234-98 ( EudraCT Number )
First Posted: May 2, 2016    Key Record Dates
Results First Posted: November 22, 2017
Last Update Posted: November 22, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Empagliflozin
Linagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action