Trial Outcomes & Findings for Investigation of the Effect of Food on the Bioavailability of a 25 mg Empagliflozin Tablet as Well as Assessment of Dose Proportionality Between 10 mg and 25 mg Empagliflozin Tablets Under Fasting Conditions. (NCT NCT01451775)

Last Updated: 2014-06-27

Results Overview

Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 hours extrapolated to infinity (AUC0-∞). The Measured Values show intra-arm variabilities, whereas the statistical analyses show inter-arm variabilities.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

1 hour (h) before study drug and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Results posted on

2014-06-27

Participant Flow

This was a randomised 3 period crossover trial. 18 patients were randomised to one of six treatment sequences and treated. The trial was open label with washout periods of at least 7 days between treatments.

Participant milestones

Participant milestones
Measure	Empa 25mg Fasted / Empa 25mg Fed / Empa 10mg Fasted Patients were administered three treatments in the following order: * A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours. * A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast * A single dose of 10 mg empa after an overnight fast of at least 10 hours.	Empa 25mg Fasted / Empa 10mg Fasted / Empa 25mg Fed Patients were administered three treatments in the following order: * A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours. * A single dose of 10 mg empa after an overnight fast of at least 10 hours. * A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast	Empa 25mg Fed / Empa 25mg Fasted / Empa 10mg Fasted Patients were administered three treatments in the following order: * A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast * A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours. * A single dose of 10 mg empa after an overnight fast of at least 10 hours.	Empa 25mg Fed / Empa 10mg Fasted / Empa 25mg Fasted Patients were administered three treatments in the following order: * A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast * A single dose of 10 mg empa after an overnight fast of at least 10 hours. * A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.	Empa 10mg Fasted / Empa 25mg Fasted / Empa 25mg Fed Patients were administered three treatments in the following order: * A single dose of 10 mg empa after an overnight fast of at least 10 hours. * A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours. * A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast	Empa 10mg Fasted / Empa 25mg Fed / Empa 25mg Fasted Patients were administered three treatments in the following order: * A single dose of 10 mg empa after an overnight fast of at least 10 hours. * A single dose of 25 mg empa after a standardised high-fat, high-caloric breakfast * A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
Overall Study STARTED	3	3	3	3	3	3
Overall Study COMPLETED	3	3	3	3	3	3
Overall Study NOT COMPLETED	0	0	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Investigation of the Effect of Food on the Bioavailability of a 25 mg Empagliflozin Tablet as Well as Assessment of Dose Proportionality Between 10 mg and 25 mg Empagliflozin Tablets Under Fasting Conditions.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study Overall n=18 Participants Total number of patients randomised and treated in the study. This was a randomised 3 period crossover trial. 18 patients were randomised to one of six treatment sequences and treated. The trial was open label with washout periods of at least 7 days between treatments.
Age, Continuous	36.1 years STANDARD_DEVIATION 7.6 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 hour (h) before study drug and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Population: All treated subjects who provided at least one observation in the relevant treatment periods for at least one primary pharmacokinetic (PK) endpoint without a relevant protocol deviation and who had not experienced emesis before or at 2 times median tmax in at least one of the two relevant treatment periods.

Outcome measures

Outcome measures
Measure	Empa 25 mg Fasted n=18 Participants A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.	Empa 25 mg Fed n=17 Participants A single dose of 25 mg empagliflozin (empa) after a standardised high-fat, high-caloric breakfast.	Empa 10 mg Fasted n=18 Participants A single dose of 10 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
Area Under the Curve 0 to Infinity (AUC0-∞)	5380 nmol*h/L Geometric Coefficient of Variation 26.0	4520 nmol*h/L Geometric Coefficient of Variation 24.8	2280 nmol*h/L Geometric Coefficient of Variation 27.0

PRIMARY outcome

Timeframe: 1 hour (h) before study drug and 20 minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h and 72h after drug administration

Maximum measured concentration of empagloflozin (empa) in plasma, per period. The Measured Values show intra-arm variabilities, whereas the statistical analyses show inter-arm variabilities.

Outcome measures

Outcome measures
Measure	Empa 25 mg Fasted n=18 Participants A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.	Empa 25 mg Fed n=17 Participants A single dose of 25 mg empagliflozin (empa) after a standardised high-fat, high-caloric breakfast.	Empa 10 mg Fasted n=18 Participants A single dose of 10 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
Maximum Measured Concentration (Cmax)	837 nmol/L Geometric Coefficient of Variation 27.8	523 nmol/L Geometric Coefficient of Variation 27.7	365 nmol/L Geometric Coefficient of Variation 27.7

SECONDARY outcome

Timeframe: Screening until end of trial, average of 45 days

Population: Treated Set(TS): TS includes all subjects who have taken at least 1 dose of trial medication

Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry, haematology, urinanalysis and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as adverse events (AEs). Time frame for AE reporting includes the period of first drug administration until end of study. A more detailed definition of the used time frame and MedDRA Version can be found in the AE section.

Outcome measures

Outcome measures
Measure	Empa 25 mg Fasted n=18 Participants A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.	Empa 25 mg Fed n=18 Participants A single dose of 25 mg empagliflozin (empa) after a standardised high-fat, high-caloric breakfast.	Empa 10 mg Fasted n=18 Participants A single dose of 10 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator.	0 participants	0 participants	0 participants

Adverse Events

Empa 25 mg Fasted

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Empa 25 mg Fed

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Empa 10 mg Fasted

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Empa 25 mg Fasted n=18 participants at risk A single dose of 25 mg empagliflozin (empa) after an overnight fast of at least 10 hours.	Empa 25 mg Fed n=18 participants at risk A single dose of 25 mg empagliflozin (empa) after a standardised high-fat, high-caloric breakfast.	Empa 10 mg Fasted n=18 participants at risk A single dose of 10 mg empagliflozin (empa) after an overnight fast of at least 10 hours.
Ear and labyrinth disorders Vertigo	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days
Gastrointestinal disorders Abdominal pain	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days
Gastrointestinal disorders Nausea	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days
Gastrointestinal disorders Vomiting	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days
Infections and infestations Rhinitis	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days
Musculoskeletal and connective tissue disorders Myosclerosis	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days
Nervous system disorders Headache	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	11.1% 2/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days
Nervous system disorders Migraine	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days
Nervous system disorders Presyncope	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days
Skin and subcutaneous tissue disorders Neurodermatitis	5.6% 1/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days	0.00% 0/18 • Drug administration until beginning of next sequence/end of trial, average of 24 days

Additional Information

Boehringer Ingelheim Call Center

boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place