NCT02758171

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

Completed Phase 1 Results posted Last updated 22 November 2017

What this trial tests

Phase 1 trial testing Empagliflozin in Healthy in 56 participants. Completed in 3 August 2016.

Timeline

17 May 2016

Primary endpoint
29 July 2016

3 August 2016

Quick facts

Lead sponsor	Boehringer Ingelheim
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	treatment
Enrollment	56
Start date	17 May 2016
Primary completion	29 July 2016
Estimated completion	3 August 2016
Sites	1 location across Germany

Drugs / interventions tested

• Empagliflozin (empagliflozin) — full drug profile →
• Linagliptin (LINAGLIPTIN) — full drug profile →

Conditions studied

• Healthy — all drugs for Healthy →

Sponsor

Boehringer Ingelheim — full company profile →

Who can join

Adults 18 to 55, any sex, with Healthy. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

Group	Value	95% CI
FDC (10 mg Empagliflozin and 5 mg Linagliptin)	2550	± 18.0
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets	2510	± 19.9

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

Group	Value	95% CI
FDC (10 mg Empagliflozin and 5 mg Linagliptin)	281	± 22.5
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets	283	± 23.3

Cmax (Maximum Measured Concentration of Empagliflozin Analyte in Plasma) Primary · 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).

Group	Value	95% CI
FDC (10 mg Empagliflozin and 5 mg Linagliptin)	370	± 23.9
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets	365	± 23.9

Cmax (Maximum Measured Concentration of Linagliptin Analyte in Plasma) Primary · 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).

Group	Value	95% CI
FDC (10 mg Empagliflozin and 5 mg Linagliptin)	9.33	± 36.2
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets	8.73	± 37.1

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

Group	Value	95% CI
FDC (10 mg Empagliflozin and 5 mg Linagliptin)	2580	± 18.0
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets	2550	± 19.8

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

Group	Value	95% CI
FDC (10 mg Empagliflozin and 5 mg Linagliptin)	451	± 25.9
Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets	462	± 29.2

Adverse events — posted to ClinicalTrials.gov

Time frame: From first drug administration until 1 day after last drug administration, up to 77 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

FDC (10 mg Empagliflozin and 5 mg Linagliptin)

Serious: 0/56 (0%)

Deaths: —

Empagliflozin (10 mg) + Linagliptin (5 mg) Single Tablets

Serious: 0/54 (0%)

Deaths: —

Other adverse events (1 terms — click to expand)

Reaction	System	FDC (10 mg Empagliflozin a…	Empagliflozin (10 mg) + Li…
Headache	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT02758171 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.