Trial Outcomes & Findings for 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 (NCT NCT03629054)
NCT ID: NCT03629054
Last Updated: 2020-02-21
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
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.
Results posted on
2020-02-21
Participant Flow
It was planned to include healthy participants in this randomised, open-label, two-way crossover trial with 2 treatments (test treatment (T) and reference treatment (R)) and 2 treatment sequences (TR or RT) in order to compare the treatment T to the treatment R under fed conditions. They were recruited from the volunteers' pool of the study site.
All participants were screened for eligibility to participate in the trial and to ensure that all participants met all inclusion/exclusion criteria. Participants were not to be included in the trial if any of the specific exclusion criteria were met.
Participant milestones
| Measure |
Test Treatment (T)/ Reference Treatment (R)
Participants were administered 2 fixed dose combination (FDC) coated tablets of 5 milligram (mg) empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin extended release (XR) orally as a single dose in the fed state in period 1, followed by the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state in period 2. The T and R treatments were separated by a washout period of at least 35 days.
|
Reference Treatment (R)/ Test Treatment (T)
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state in period 1 and followed by 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state in period 2. The T and R treatments were separated by a washout period of at least 35 days.
|
|---|---|---|
|
Period 1 (4 Days)
STARTED
|
15
|
15
|
|
Period 1 (4 Days)
COMPLETED
|
15
|
15
|
|
Period 1 (4 Days)
NOT COMPLETED
|
0
|
0
|
|
Wasout Period (35 Days)
STARTED
|
15
|
15
|
|
Wasout Period (35 Days)
COMPLETED
|
15
|
15
|
|
Wasout Period (35 Days)
NOT COMPLETED
|
0
|
0
|
|
Period 2 (4 Days)
STARTED
|
15
|
15
|
|
Period 2 (4 Days)
Treated
|
15
|
14
|
|
Period 2 (4 Days)
COMPLETED
|
15
|
14
|
|
Period 2 (4 Days)
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Test Treatment (T)/ Reference Treatment (R)
Participants were administered 2 fixed dose combination (FDC) coated tablets of 5 milligram (mg) empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin extended release (XR) orally as a single dose in the fed state in period 1, followed by the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state in period 2. The T and R treatments were separated by a washout period of at least 35 days.
|
Reference Treatment (R)/ Test Treatment (T)
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state in period 1 and followed by 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state in period 2. The T and R treatments were separated by a washout period of at least 35 days.
|
|---|---|---|
|
Period 2 (4 Days)
Not treated
|
0
|
1
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Test Treatment (T)/ Reference Treatment (R)
n=15 Participants
Participants were administered 2 fixed dose combination (FDC) coated tablet of 5 milligram(mg) empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin extended release (XR) orally in the fed state in period 1, followed by free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR in the fed state in period 2. The T and R treatments were separated by a washout period of at least 35 days.
|
Reference Treatment (R)/ Test Treatment (T)
n=15 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state in period 1 and followed by 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state in period 2. The T and R treatments were separated by a washout period of at least 35 days.
|
Total
n=30 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
46.9 Years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
41.5 Years
STANDARD_DEVIATION 9.7 • n=7 Participants
|
44.2 Years
STANDARD_DEVIATION 9.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
15 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.Population: Pharmacokinetic parameter set (PKS): PKS included all subjects in the treated set (TS) who provided at least one primary or secondary PK parameter that was not excluded due to protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
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.
Outcome measures
| Measure |
Test Treatment (T)
n=29 Participants
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
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)
|
2134.53 nanomole*hour/litre (nmol*h/L)
Standard Error 1.03
|
2125.57 nanomole*hour/litre (nmol*h/L)
Standard Error 1.03
|
PRIMARY outcome
Timeframe: 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.Population: PKS
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.
Outcome measures
| Measure |
Test Treatment (T)
n=29 Participants
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
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)
|
21687.12 nanogram*h/mL (ng*h/mL)
Standard Error 1.04
|
22748.21 nanogram*h/mL (ng*h/mL)
Standard Error 1.04
|
PRIMARY outcome
Timeframe: 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.Population: PKS
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.
Outcome measures
| Measure |
Test Treatment (T)
n=29 Participants
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Linagliptin in Plasma Over the Time Interval From 0 to 72 Hours (h) (AUC0-72)
|
270.19 nmol*h/L
Standard Error 1.03
|
269.77 nmol*h/L
Standard Error 1.03
|
PRIMARY outcome
Timeframe: 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.Population: PKS
Cmax, maximum measured concentration of the empagliflozin in plasma is presented. SE is a geometric SE.
Outcome measures
| Measure |
Test Treatment (T)
n=29 Participants
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
Maximum Measured Concentration of the Empagliflozin in Plasma (Cmax)
|
209.67 nanomole/Litre (nmol/ L)
Standard Error 1.05
|
226.50 nanomole/Litre (nmol/ L)
Standard Error 1.05
|
PRIMARY outcome
Timeframe: 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.Population: PKS
Cmax, maximum measured concentration of the linagliptin in plasma is presented. SE is a geometric SE.
Outcome measures
| Measure |
Test Treatment (T)
n=29 Participants
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
Maximum Measured Concentration of the Linagliptin in Plasma (Cmax)
|
7.02 nanomole/Litre (nmol/ L)
Standard Error 1.05
|
7.21 nanomole/Litre (nmol/ L)
Standard Error 1.05
|
PRIMARY outcome
Timeframe: 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.Population: PKS
Cmax, maximum measured concentration of the metformin in plasma is presented. SE is a geometric SE.
Outcome measures
| Measure |
Test Treatment (T)
n=29 Participants
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
Maximum Measured Concentration of the Metformin in Plasma (Cmax)
|
1853.03 nanogram/ millilitre (ng/ mL)
Standard Error 1.04
|
1767.69 nanogram/ millilitre (ng/ mL)
Standard Error 1.04
|
SECONDARY outcome
Timeframe: 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.Population: PKS
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.
Outcome measures
| Measure |
Test Treatment (T)
n=29 Participants
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Empagliflozin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
|
2182.26 nmol*h/L
Standard Error 1.03
|
2166.54 nmol*h/L
Standard Error 1.03
|
SECONDARY outcome
Timeframe: 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.Population: PKS
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.
Outcome measures
| Measure |
Test Treatment (T)
n=29 Participants
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Linagliptinin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
|
471.40 nmol*h/L
Standard Error 1.05
|
455.13 nmol*h/L
Standard Error 1.05
|
SECONDARY outcome
Timeframe: 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.Population: PKS
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.
Outcome measures
| Measure |
Test Treatment (T)
n=29 Participants
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
Area Under the Concentration-time Curve of the Metformin Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
|
22288.72 ng*h/mL
Standard Error 1.04
|
23280.48 ng*h/mL
Standard Error 1.04
|
SECONDARY outcome
Timeframe: All adverse events (AEs) which occurred through the treatment phase and throughout the residual effect period (REP), up to 7 days.Population: TS
Percentage of patients with investigator defined drug-related AEs are presented.
Outcome measures
| Measure |
Test Treatment (T)
n=29 Participants
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 Participants
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
Percentage of Patients With Drug-related Adverse Events (AEs)
|
7 Participants
|
6 Participants
|
Adverse Events
Test Treatment (T)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Reference Treatment (R)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Test Treatment (T)
n=29 participants at risk
Participants were administered 2 FDC coated tablets of 5 mg empagliflozin/ 2.5 mg linagliptin/ 1000 mg metformin XR orally as a single dose in the fed state.
|
Reference Treatment (R)
n=30 participants at risk
Participants were administered the free combination of 1 film-coated tablet of 10 mg empagliflozin, 1 film-coated tablet of 5 mg linagliptin and 4 film-coated tablets of 500 mg metformin XR orally as single dose in the fed state.
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
13.8%
4/29 • 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.
|
10.0%
3/30 • 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.
|
|
Infections and infestations
Nasopharyngitis
|
6.9%
2/29 • 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.
|
3.3%
1/30 • 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.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
3.4%
1/29 • 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.
|
6.7%
2/30 • 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.
|
|
Nervous system disorders
Headache
|
13.8%
4/29 • 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.
|
6.7%
2/30 • 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.
|
Additional Information
Boehringer Ingelheim, Call Centre
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place