NCT03629054

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

Completed Phase 1 Results posted Last updated 21 February 2020

What this trial tests

Phase 1 trial testing Empagliflozin, Metformin HCl, Linagliptin (fixed dose combination) in Healthy in 30 participants. Completed in 5 November 2018.

Timeline

27 August 2018

Primary endpoint
5 November 2018

5 November 2018

Quick facts

Lead sponsor	Boehringer Ingelheim
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	treatment
Enrollment	30
Start date	27 August 2018
Primary completion	5 November 2018
Estimated completion	5 November 2018
Sites	1 location across Germany

Drugs / interventions tested

• Empagliflozin, Metformin HCl, Linagliptin (fixed dose combination) — full drug profile →
• Empagliflozin (empagliflozin) — full drug profile →
• Linagliptin (LINAGLIPTIN) — full drug profile →
• Metformin HCl

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.

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) Primary · 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.

Group	Value	95% CI
Test Treatment (T)	2134.53	± 1.03
Reference Treatment (R)	2125.57	± 1.03

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) Primary · 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.

Group	Value	95% CI
Test Treatment (T)	21687.12	± 1.04
Reference Treatment (R)	22748.21	± 1.04

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

Group	Value	95% CI
Test Treatment (T)	270.19	± 1.03
Reference Treatment (R)	269.77	± 1.03

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

Group	Value	95% CI
Test Treatment (T)	209.67	± 1.05
Reference Treatment (R)	226.50	± 1.05

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

Group	Value	95% CI
Test Treatment (T)	7.02	± 1.05
Reference Treatment (R)	7.21	± 1.05

Maximum Measured Concentration of the Metformin in Plasma (Cmax) Primary · 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.

Group	Value	95% CI
Test Treatment (T)	1853.03	± 1.04
Reference Treatment (R)	1767.69	± 1.04

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

Group	Value	95% CI
Test Treatment (T)	2182.26	± 1.03
Reference Treatment (R)	2166.54	± 1.03

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

Group	Value	95% CI
Test Treatment (T)	471.40	± 1.05
Reference Treatment (R)	455.13	± 1.05

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

Group	Value	95% CI
Test Treatment (T)	22288.72	± 1.04
Reference Treatment (R)	23280.48	± 1.04

Percentage of Patients With Drug-related Adverse Events (AEs) Secondary · 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.

Group	Value	95% CI
Test Treatment (T)	7
Reference Treatment (R)	6

Adverse events — posted to ClinicalTrials.gov

Time frame: All adverse events (AEs) which occurred through the treatment phase and throughout the residual effect period (REP), up to 7 days. All cause mortality and serious AEs are considering the entire duration of the trial, 49 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Test Treatment (T)

Serious: 0/29 (0%)

Deaths: 0/29

Reference Treatment (R)

Serious: 0/30 (0%)

Deaths: 0/30

Other adverse events (4 terms — click to expand)

Reaction	System	Test Treatment (T)	Reference Treatment (R)
Nausea	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—

Data from ClinicalTrials.gov NCT03629054 adverse events section.

Sponsor's own description

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.

Publications & conference data

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