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

Bioequivalence of a Low Strength Fixed Dose Combination Tablet of Empagliflozin/Linagliptin/Metformin Extended Release Compared to the Free Combination of Empagliflozin, Linagliptin, and Metformin Extended Release Tablets Following Oral Administration in Healthy Male and Female Subjects (an Open-label, Randomised, Single-dose, Two-period, Two-sequence Crossover Study)

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Empagliflozin, Metformin HCl, Linagliptin (fixed dose combination); Drug: Empagliflozin; Drug: Linagliptin; Drug: Metformin HCl

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 51 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

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: Test treatment (T); Low strength empagliflozin/linagliptin/metformin XR fixed dose combination tablet	Drug: Empagliflozin, Metformin HCl, Linagliptin (fixed dose combination); single dose; Other Names: TRIJARDY® XR
Experimental: Reference treatment (R); Single tablets of empagliflozin + linagliptin + metformin XR	Drug: Empagliflozin; single dose; Drug: Linagliptin; single dose; Drug: Metformin HCl; single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	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.
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)	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.	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.
Area Under the Concentration-time Curve of the Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (h) (AUC0-72)	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.	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.
Maximum Measured Concentration of the Empagliflozin in Plasma (Cmax)	Cmax, maximum measured concentration of the empagliflozin in plasma is presented. SE is a geometric SE.	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.
Maximum Measured Concentration of the Linagliptin in Plasma (Cmax)	Cmax, maximum measured concentration of the linagliptin in plasma is presented. SE is a geometric SE.	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.
Maximum Measured Concentration of the Metformin in Plasma (Cmax)	Cmax, maximum measured concentration of the metformin in plasma is presented. SE is a geometric SE.	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-time Curve of the Empagliflozin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	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.	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.
Area Under the Concentration-time Curve of the Linagliptinin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	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.	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.
Area Under the Concentration-time Curve of the Metformin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)	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.	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.
Percentage of Patients With Drug-related Adverse Events (AEs)	Percentage of patients with investigator defined drug-related AEs are presented.	All adverse events (AEs) which occurred through the treatment phase and throughout the residual effect period (REP), up to 7 days.

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): August 27, 2018
• Primary Completion (Actual): November 5, 2018
• Study Completion (Actual): November 5, 2018

Study Registration Dates

• First Submitted: August 9, 2018
• First Submitted That Met QC Criteria: August 9, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): February 21, 2020
• Last Update Submitted That Met QC Criteria: February 6, 2020
• Last Verified: February 1, 2020

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; Metformin; Empagliflozin; Linagliptin
• Other Study ID Numbers: 1361-0011; 2018-001266-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). Requestors can use the following link http:// trials.boehringer-ingelheim.com/ to:

1. find information in order to request access to clinical study data, for listed studies.
2. request access to clinical study documents that meet criteria, and upon a signed 'Document Sharing Agreement'.

Drug and device information, study documents

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