This Study in Healthy People Tests Whether Taking a Low Strength of Empagliflozin, Linagliptin, and Metformin Together in 1 Pill is the Same as Taking Them in Separate Pills

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Empagliflozin, Metformin HCl, Linagliptin (fixed dose combination); Drug: Empagliflozin; Drug: Linagliptin; Drug: Metformin HCl

• Registration Number: NCT03629054
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The primary objective of this trial is to establish the bioequivalence of two empagliflozin/linagliptin/metformin extended release (XR) fixed dose combination (FDC) tablets (Test, T) compared with the same doses of the individual components given in separate tablets (Reference, R) when administered together after a high-fat, high-calorie meal.

The assessment of safety and tolerability will be the secondary objective of this trial.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-08-09
• Study First Submitted QC: 2018-08-09
• Study First Posted: 2018-08-14
• Study Start: 2018-08-27
• Primary Completion: 2018-11-05
• Study Completion: 2018-11-05
• Status Verified: 2020-02
• Results First Submitted: 2020-02-06
• Results First Submitted QC: 2020-02-06
• Last Update Submitted: 2020-02-06
• Results First Posted: 2020-02-21
• Last Update Posted: 2020-02-21

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.)
• 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 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
• 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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Test treatment (T)	Empagliflozin, Metformin HCl, Linagliptin (fixed dose combination)	Low strength empagliflozin/linagliptin/metformin XR fixed dose combination tablet
Reference treatment (R)	Linagliptin	Single tablets of empagliflozin + linagliptin + metformin XR
Reference treatment (R)	Empagliflozin	Single tablets of empagliflozin + linagliptin + metformin XR
Reference treatment (R)	Metformin HCl	Single tablets of empagliflozin + linagliptin + metformin XR

Primary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve of the Empagliflozin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	Pharmacokinetic (PK) samples were collected 1:30 hours:minutes (h:m) 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 h:m after drug administration.	AUC0-tz, Area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 to the last quantifiable data point is presented. Standard error (SE) is a geometric SE.
Area Under the Concentration-time Curve of the Metformin in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)	Pharmacokinetic (PK) samples were collected 1:30 hours:minutes (h:m) 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 h:m after drug administration.	AUC0-tz, Area under the concentration-time curve of the metformin in plasma over the time interval from 0 to the last quantifiable data point is presented. Standard error (SE) is a geometric SE.
Maximum Measured Concentration of the Empagliflozin in Plasma (Cmax)	PK samples were collected 1:30 h:m 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 h:m after drug administration.	Cmax, maximum measured concentration of the empagliflozin in plasma is presented. SE is a geometric SE.
Maximum Measured Concentration of the Linagliptin in Plasma (Cmax)	PK samples were collected 1:30 h:m 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 h:m after drug administration.	Cmax, maximum measured concentration of the linagliptin in plasma is presented. SE is a geometric SE.
Area Under the Concentration-time Curve of the Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (h) (AUC0-72)	PK samples were collected 1:30 h:m 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 h:m after drug administration.	AUC0-72, area under the concentration-time curve of the linagliptin in plasma over the time interval from 0 to 72 h is presented. SE is a geometric SE.
Maximum Measured Concentration of the Metformin in Plasma (Cmax)	PK samples were collected 1:30 h:m 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 h:m after drug administration.	Cmax, maximum measured concentration of the metformin in plasma is presented. SE is a geometric SE.

Secondary Outcome Measures

Name	Time	Method
Area Under the Concentration-time Curve of the Empagliflozin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	PK samples were collected 1:30 h:m 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 h:m after drug administration.	AUC0-∞, area under the concentration-time curve of the empagliflozin in plasma over the time interval from 0 extrapolated to infinity is presented. SE is a geometric SE.
Area Under the Concentration-time Curve of the Metformin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	PK samples were collected 1:30 h:m 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 h:m after drug administration.	AUC0-∞, area under the concentration-time curve of the metformin in plasma over the time interval from 0 extrapolated to infinity is presented. SE is a geometric SE.
Area Under the Concentration-time Curve of the Linagliptinin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	PK samples were collected 1:30 h:m 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 h:m after drug administration.	AUC0-∞, area under the concentration-time curve of the linagliptin in plasma over the time interval from 0 extrapolated to infinity is presented. SE is a geometric SE.
Percentage of Patients With Drug-related Adverse Events (AEs)	All adverse events (AEs) which occurred through the treatment phase and throughout the residual effect period (REP), up to 7 days.	Percentage of patients with investigator defined drug-related AEs are presented.

Trial Locations

Locations (1)

Humanpharmakologisches Zentrum Biberach; 🇩🇪 Biberach, Germany