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)
Overview
- Phase
- Phase 1
- Intervention
- Empagliflozin, Metformin HCl, Linagliptin (fixed dose combination)
- Conditions
- Healthy
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 6 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Exclusion Criteria
- Not provided
Arms & Interventions
Test treatment (T)
Low strength empagliflozin/linagliptin/metformin XR fixed dose combination tablet
Intervention: Empagliflozin, Metformin HCl, Linagliptin (fixed dose combination)
Reference treatment (R)
Single tablets of empagliflozin + linagliptin + metformin XR
Intervention: Empagliflozin
Reference treatment (R)
Single tablets of empagliflozin + linagliptin + metformin XR
Intervention: Linagliptin
Reference treatment (R)
Single tablets of empagliflozin + linagliptin + metformin XR
Intervention: Metformin HCl
Outcomes
Primary Outcomes
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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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)
Time Frame: 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 Outcomes
- 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.)
- 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.)
- 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.)
- 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.)