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OpenTrials
Completed

NCT Number: NCT02821910

Relative Bioavailability of 2 Fixed Dose Combinations of Empagliflozin/Linagliptin/Metformin Extended Release Compared With Single Tablets

The purpose of this trial is to demonstrate the relative bioavailability of 2 newly developed fixed dose combinations (FDC) tablets containing empagliflozin, linagliptin & metformin extended release (XR) and the single tablets of empagliflozin, linagliptin and metformin XR administered simultaneously.

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Key information

Conditions

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Humanpharmakologisches Zentrum Biberach

Biberach, 88397, Germany

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Healthy male or female subjects according to the investigator's assessment, based on a complete medical history including a physical examination, vital signs (blood pressure, pulse rate), 12-lead electrocardiogram, 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 GCP 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 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, pulse rate or electrocardiogram) 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

Treatment and study plan

High dose FDC Empagliflozin/Linagliptin/Metformin XR, fed

Drug

High dose Empagliflozin/Linagliptin/Metformin extended release (XR) fixed dose combination (FDC) tablet

1 tab Empagliflozin +1 tab Linagliptin +2 tabs Metformin XR

Drug

1x Empagliflozin + 1x Linagliptin + 2x Metformin extended release (XR) tablets

High dose FDC Empagliflozin/Linagliptin/Metformin XR, fasted

Drug

High dose Empagliflozin/Linagliptin/Metformin extended release (XR) fixed dose combination (FDC) tablet

Low dose FDC Empagliflozin/Linagliptin/Metformin XR, fed

Drug

Low dose Empagliflozin/Linagliptin/Metformin extended release (XR) fixed dose combination (FDC) tablet

Primary outcomes

  1. Area Under the Concentration-time Curve of Empagliflozin in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Concentration (AUC0-tz)

    Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration

    Area under the concentration-time curve of Empagliflozin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz) is presented.

    Plasma concentrations and/or parameters of a subject were 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 subject's experiencing emesis)
    • A pre-dose concentration was >5% of the Cmax value measured in that subject
    • Missing samples or concentration data at important phases of PK disposition curve
  2. Area Under the Concentration-time Curve of Metformin in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Concentration (AUC0-tz)

    Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration

    Area under the concentration-time curve of Metformin in plasma over the time interval from 0 to the time of the last quantifiable concentration (AUC0-tz) is presented

  3. Maximum Measured Concentration of Empagliflozin in Plasma (Cmax)

    Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration

    Maximum measured concentration of Empagliflozin in plasma (Cmax) is presented

  4. Maximum Measured Concentration of Metformin in Plasma (Cmax)

    Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration

    Maximum measured concentration of Metformin in plasma (Cmax) is presented

  5. Maximum Measured Concentration of Linagliptin in Plasma (Cmax)

    Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration

    Maximum measured concentration of Linagliptin in plasma (Cmax) is presented

  6. Area Under the Concentration-time Curve of Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (AUC0-72)

    Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration

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

Secondary outcomes

  1. Area Under the Concentration-time Curve of the Empagliflozin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)

    Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration

    Area under the concentration-time curve of the Empagliflozin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented

  2. Area Under the Concentration-time Curve of the Metformin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)

    Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration

    Area under the concentration-time curve of the Metformin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented

  3. Area Under the Concentration-time Curve of the Linagliptin in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)

    Time frame: 1.5 hours (h) before drug administration and 0.5h, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 5h, 6h, 7h, 8h,10h, 12h, 24h, 34h, 48h, and 72h after drug administration

    Area under the concentration-time curve of the Linagliptin in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) is presented

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Collaborators

  • Eli Lilly and Company

Registry information

Official study title

Relative Bioavailability of Two FDC Tablet Strengths of Empagliflozin/Linagliptin/Metformin Extended Release Compared to the Free Combination of Empagliflozin, Linagliptin and Metformin Extended Release Following Oral Administration in Healthy Male and Female Subjects (an Open-label, Randomised, Single-dose, Two-period, Two-sequence Crossover Study)

Important dates

Study start
2016
Primary completion
2016
Study completion
2016
First posted
Jul 4, 2016
Registry last updated
Mar 5, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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