Relative Bioavailability of Empagliflozin (BI 10773) and Ramipril Administered Together Compared to Empagliflozin (BI 10773) and Ramipril Alone in Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: BI 10773; Drug: Ramipril

• Registration Number: NCT01284621
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

Primary objective:To investigate if BI 10773 affects the pharmacokinetics of ramipril and if ramipril affects the pharmacokinetics of BI 10773.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01
• Study First Submitted: 2011-01-20
• Study First Submitted QC: 2011-01-26
• Study First Posted: 2011-01-27
• Primary Completion: 2011-03
• Results First Submitted: 2014-05-16
• Status Verified: 2014-06
• Results First Submitted QC: 2014-06-23
• Last Update Submitted: 2014-06-23
• Results First Posted: 2014-07-22
• Last Update Posted: 2014-07-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 23

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
BI 10773	BI 10773	1 tablet per days for 5 days, oral administration with 240 mL water for each treatment
BI 10773 + Ramipril	BI 10773	1 tablet BI 10773 and 1 tablet on day 1 and 2 tablets ramipril per day on day 2-5, oral administration with 240 mL water for each treatment
Ramipril	Ramipril	1 tablet on day 1 and 2 tablets per day on day 2-5, oral administration with 240 mL water for each treatment
BI 10773 + Ramipril	Ramipril	1 tablet BI 10773 and 1 tablet on day 1 and 2 tablets ramipril per day on day 2-5, oral administration with 240 mL water for each treatment

Primary Outcome Measures

Name	Time	Method
Total Empa: Area Under the Curve at Steady-state Over a Uniform Dosing Interval (AUCτ,ss)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Area under the concentration-time curve of the analyte in plasma at steady-state over a uniform dosing interval τ, of empagliflozin (empa).
Total Empa: Maximum Measured Concentration (Cmax,ss)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Maximum measured concentration of the analyte in plasma at steady-state over a uniform dosing interval, τ, of empagliflozin (empa).
Total Ramiprilat: Area Under the Curve at Steady-state Over a Uniform Dosing Interval (AUCτ,ss).	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Area under the concentration-time curve of the analyte in plasma at steady-state over a uniform dosing interval τ, of ramiprilat (active metabolite of ramipril).
Total Ramipril: Area Under the Curve at Steady-state Over a Uniform Dosing Interval (AUCτ,ss).	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Area under the concentration-time curve of the analyte in plasma at steady-state over a uniform dosing interval τ, of ramipril.
Total Ramipril: Maximum Measured Concentration (Cmax,ss)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Maximum measured concentration of the analyte in plasma at steady-state over a uniform dosing interval, τ, of ramipril.
Total Ramiprilat: Maximum Measured Concentration (Cmax,ss)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Maximum measured concentration of the analyte in plasma at steady-state over a uniform dosing interval, τ, of ramiprilat.

Secondary Outcome Measures

Name	Time	Method
Time From Last Dosing to the Maximum Measured Concentration (Tmax,ss)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Time from last dosing to the maximum measured concentration of the analyte in plasma at steady state.
Empa: Predose Concentration Prior to Administration of the Nth Dose (Cpre,N)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Predose concentration of the analyte in plasma prior to administration of the Nth dose, of empagliflozin.
Terminal Rate Constant (λz,ss)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Terminal rate constant in plasma at steady-state
Mean Residence Time (MRTpo,ss)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Mean residence time of the analyte in the body after oral administration at steady-state.
Apparent Clearance After Extravascular Administration (CL/Fss)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Apparent clearance of the analyte in plasma after extravascular administration at steady-state.
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Tolerability	From drug administration until end of washout period (36 days)	Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry and assessment tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as adverse events.
Ramiprilat: Predose Concentration Prior to Administration of the Nth Dose (Cpre,N)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Predose concentration of the analyte in plasma prior to administration of the Nth dose, of ramiprilat.; Note, predose concentrations for ramipril were all below the limit of quantification (BLQ) and therefore the predose concentration of the analyte in plasma prior to administration of the Nth dose, of ramipril was not analysed.
Terminal Half-life (T 1/2,ss)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Terminal half-life of the analyte in plasma at steady-state.
Apparent Volume of Distribution During the Terminal Phase (Vz/Fss)	0 hours (h), 20 minutes (min), 40 min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 36h, 48h and 72h after drug administration on day 5. In addition pre-dose samples, 5 minutes predose, were collected on days 1 to 4	Apparent volume of distribution at steady-state during the terminal phase λz following an extravascular dose.

Trial Locations

Locations (1)

1245.45.1 Boehringer Ingelheim Investigational Site; 🇩🇪 Biberach, Germany