Clinical trial NCT01284621: Relative Bioavailability of Empagliflozin (BI 10773) and Ramipril Administered Together Compared to Empagliflozin (BI 10773) and Ramipril Alone in Healthy Volunteers
Official title: Relative Bioavailability of Multiple Oral Doses of BI 10773 (25 mg) and Ramipril (5 mg) Administered Together Compared to Multiple Oral Doses of BI 10773 (25 mg) Alone and Ramipril (5 mg) Alone in Healthy Male and Female Volunteers (an Open Label, Randomised, Three Way Crossover, Clinical Phase I Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-01-27
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: Inclusion criteria:

1. healthy male and female subjects

Exclusion criteria:

1. Any relevant deviation from healthy conditions.

Primary outcomes:
measure: Total Empa: Area Under the Curve at Steady-state Over a Uniform Dosing Interval (AUCτ,ss)
timeFrame: 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
measure: Total Empa: Maximum Measured Concentration (Cmax,ss)
timeFrame: 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
measure: Total Ramipril: Area Under the Curve at Steady-state Over a Uniform Dosing Interval (AUCτ,ss).
timeFrame: 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
measure: Total Ramipril: Maximum Measured Concentration (Cmax,ss)
timeFrame: 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
measure: Total Ramiprilat: Area Under the Curve at Steady-state Over a Uniform Dosing Interval (AUCτ,ss).
timeFrame: 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
measure: Total Ramiprilat: Maximum Measured Concentration (Cmax,ss)
timeFrame: 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
Secondary outcomes:
measure: Empa: Predose Concentration Prior to Administration of the Nth Dose (Cpre,N)
timeFrame: 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
measure: Ramiprilat: Predose Concentration Prior to Administration of the Nth Dose (Cpre,N)
timeFrame: 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
measure: Time From Last Dosing to the Maximum Measured Concentration (Tmax,ss)
timeFrame: 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
measure: Terminal Rate Constant (λz,ss)
timeFrame: 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
measure: Terminal Half-life (T 1/2,ss)
timeFrame: 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
measure: Mean Residence Time (MRTpo,ss)
timeFrame: 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
measure: Apparent Clearance After Extravascular Administration (CL/Fss)
timeFrame: 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
measure: Apparent Volume of Distribution During the Terminal Phase (Vz/Fss)
timeFrame: 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
measure: Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Tolerability
timeFrame: From drug administration until end of washout period (36 days)
Other outcomes:
Locations:
city: Biberach
country: Germany
facility: 1245.45.1 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Macha S, Sennewald R, Rose P, Schoene K, Pinnetti S, Woerle HJ, Broedl UC. Lack of clinically relevant drug-drug interaction between empagliflozin, a sodium glucose cotransporter 2 inhibitor, and verapamil, ramipril, or digoxin in healthy volunteers. Clin Ther. 2013 Mar;35(3):226-35. doi: 10.1016/j.clinthera.2013.02.015.