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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01284621
First received: January 20, 2011
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Healthy
Drug: BI 10773
Drug: Ramipril
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Total Empa: Area Under the Curve at Steady-state Over a Uniform Dosing Interval (AUCτ,ss) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Maximum measured concentration of the analyte in plasma at steady-state over a uniform dosing interval, τ, of empagliflozin (empa).

  • Total Ramipril: Area Under the Curve at Steady-state Over a Uniform Dosing Interval (AUCτ,ss). [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Maximum measured concentration of the analyte in plasma at steady-state over a uniform dosing interval, τ, of ramipril.

  • Total Ramiprilat: Area Under the Curve at Steady-state Over a Uniform Dosing Interval (AUCτ,ss). [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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 Ramiprilat: Maximum Measured Concentration (Cmax,ss) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Maximum measured concentration of the analyte in plasma at steady-state over a uniform dosing interval, τ, of ramiprilat.


Secondary Outcome Measures:
  • Empa: Predose Concentration Prior to Administration of the Nth Dose (Cpre,N) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Predose concentration of the analyte in plasma prior to administration of the Nth dose, of empagliflozin.

  • Ramiprilat: Predose Concentration Prior to Administration of the Nth Dose (Cpre,N) [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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.


  • Time From Last Dosing to the Maximum Measured Concentration (Tmax,ss) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Time from last dosing to the maximum measured concentration of the analyte in plasma at steady state.

  • Terminal Rate Constant (λz,ss) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Terminal rate constant in plasma at steady-state

  • Terminal Half-life (T 1/2,ss) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Terminal half-life of the analyte in plasma at steady-state.

  • Mean Residence Time (MRTpo,ss) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Mean residence time of the analyte in the body after oral administration at steady-state.

  • Apparent Clearance After Extravascular Administration (CL/Fss) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Apparent clearance of the analyte in plasma after extravascular administration at steady-state.

  • Apparent Volume of Distribution During the Terminal Phase (Vz/Fss) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Apparent volume of distribution at steady-state during the terminal phase λz following an extravascular dose.

  • Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Tolerability [ Time Frame: From drug administration until end of washout period (36 days) ] [ Designated as safety issue: No ]
    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.


Enrollment: 23
Study Start Date: January 2011
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 10773
1 tablet per days for 5 days, oral administration with 240 mL water for each treatment
Drug: BI 10773
medium dose oral administration
Ramipril
1 tablet on day 1 and 2 tablets per day on day 2-5, oral administration with 240 mL water for each treatment
Drug: Ramipril
Low dose oral administration on day 1
Drug: Ramipril
Medium dose oral administration on day 2-5
BI 10773 + 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
Drug: BI 10773
medium dose, oral administration
Drug: Ramipril
Medium dose oral administration on day 2-5
Drug: Ramipril
Low dose oral administration on day 1

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

1. healthy male and female subjects

Exclusion criteria:

1. Any relevant deviation from healthy conditions.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01284621

Locations
Germany
1245.45.1 Boehringer Ingelheim Investigational Site
Biberach, Germany
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Additional Information:
No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01284621     History of Changes
Other Study ID Numbers: 1245.45, 2010-022717-25
Study First Received: January 20, 2011
Results First Received: May 16, 2014
Last Updated: June 23, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United States: Food and Drug Administration

Additional relevant MeSH terms:
Ramipril
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 29, 2014