Assessment of the Effect of Empagliflozin (BI 10773) as Single Dose on the QT Interval in Healthy Female and Male Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01195675
First received: September 3, 2010
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

The objective of this study is to demonstrate that BI 10773 does not prolong the QT(c) interval more than placebo


Condition Intervention Phase
Healthy
Drug: BI 10773 (low)
Drug: Moxifloxacin
Drug: BI 10773 Placebo
Drug: BI 10773 (high)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Assessment of the Effect of 25 mg and 200 mg of BI 10773 as Single Dose on the QT Interval in Healthy Female and Male Subjects. A Randomised, Placebo Controlled, Double-blind, Five-period Crossover Phase-I-study With Moxifloxacin as Positive Control

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Empa 25mg: Mean QTcN Change From Baseline Between 1 and 4 Hours After Dosing [ Time Frame: 60 minutes (min), 50min and 40 min before the first dose and 1 hour (h), 1.5h, 2h, 2.5h, 3h and 4h after the first dose ] [ Designated as safety issue: No ]

    Mean QTcN (heart rate-corrected QT interval, using a study population-based approach) from the ECGs obtained between 1h to 4h following drug administration minus the mean QTcN from the baseline electrocardiogram (ECGs) obtained pre-dose at each visit, for empa 25mg.

    Note, the treatment means presented are actually adjusted means.


  • Empa 200mg: Mean QTcN Change From Baseline Between 1 and 4 Hours After Dosing [ Time Frame: 60 minutes (min), 50min and 40 min before the first dose and 1 hour (h), 1.5h, 2h, 2.5h, 3h and 4h after the first dose ] [ Designated as safety issue: No ]

    Mean QTcN (heart rate-corrected QT interval, using a study population-based approach) from the ECGs obtained between 1h to 4h following drug administration minus the mean QTcN from the baseline ECGs obtained pre-dose at each visit, for empa 200mg.

    Note, the treatment means presented are actually adjusted means.



Secondary Outcome Measures:
  • Empa 25 mg: Mean QTcN Change From Baseline Between 30 Minutes and 24 Hours After Dosing [ Time Frame: 60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose ] [ Designated as safety issue: No ]

    Mean changes from baseline in QTcN from all ECGs taken between 30 minutes and 24 hours after dosings, for empa 25 mg.

    Note, presented means are actually adjusted means.


  • Empa 200 mg: Mean QTcN Change From Baseline Between 30 Minutes and 24 Hours After Dosing [ Time Frame: 60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose ] [ Designated as safety issue: No ]

    Mean changes from baseline in QTcN from all ECGs taken between 30 minutes and 24 hours after dosings, for empa 200 mg.

    Note, presented means are actually adjusted means.


  • Mean QTcN Change From Baseline Between 2 and 4 Hours After Dosing [ Time Frame: 60 minutes (min), 50min and 40 min before the first dose and 2 hour (h), 2.5h, 3h and 4h after the first dose ] [ Designated as safety issue: No ]

    Mean changes from baseline in QTcN from all ECGs taken between 2 hours and 4 hours after dosings

    Note, the means presented are actually adjusted means.


  • Empa 25mg: Change From Mean Baseline in QTcN at Each Time Point Between 30 Minutes and 24 Hours After Dosings [ Time Frame: 60 minutes (min), 50min and 40 min before the first dose and 0.5 hour (h), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose ] [ Designated as safety issue: No ]

    Change from mean baseline in QTcN at each time point between 30 minutes and 24 hours after dosings for empa 25mg. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum upper confidence limit value over time.

    For this outcome results are presented for the 24 hour timepoint as this was when the maximum value was seen.

    Note, the presented means are actually adjusted means.


  • Empa 200mg: Change From Mean Baseline in QTcN at Each Time Point Between 30 Minutes and 24 Hours After Dosings [ Time Frame: 60 minutes (min), 50min and 40 min before the first dose and 0.5 hour (h), 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose ] [ Designated as safety issue: No ]

    Change from mean baseline in QTcN at each time point between 30 minutes and 24 hours after dosings for empa 200mg. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum upper confidence limit value over time.

    For this outcome results are presented for the 2.5 hour timepoint as this was when the maximum value was seen.

    Note, the presented means are actually adjusted means.



Other Outcome Measures:
  • Time-matched Change From Placebo in QTcN Between 30 Minutes and 24 Hours After Dosing. [ Time Frame: 60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose ] [ Designated as safety issue: No ]

    The time-matched change from placebo is defined per time point as the difference of the ECG measurement following administration of empa or moxifloxacin minus the average of the measurements obtained following the two administrations of placebo. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum mean value of all measurements.

    Results are presented for the greatest change, for empa 25mg the greatest change was seen at the 24 hour time point, for empa 200 mg and moxifloxacin the greatest change was seen at the 2.5 hour time point.


  • Placebo Corrected Change From Mean Baseline at Any Time Point Between 30 Minutes and 24 Hours After Dosings. [ Time Frame: 60 minutes (min), 50min and 40 min before the first dose and 30min, 1 hour (h), 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after the first dose ] [ Designated as safety issue: No ]

    The placebo corrected change from mean baseline is defined per time point as the difference of the change from baseline for empa or moxifloxacin minus the average change from baseline obtained for the two administrations of placebo. The clinically relevant information (and endpoint resulting from ICH E14) is shown by the maximum mean value of all measurements.

    Results are presented for the greatest change, for empa 25mg the greatest change was seen at the 24 hour time point, for empa 200 mg and moxifloxacin the greatest change was seen at the 2.5 hour time point.


  • Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator [ Time Frame: Drug administration until beginning of next sequence/end of trial, up to 48 days ] [ Designated as safety issue: No ]
    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.


Enrollment: 30
Study Start Date: August 2010
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BI 10773
single oral (high and low) dose per subject
Drug: BI 10773 (low)
single oral dose
Drug: BI 10773 (high)
single oral dose
Placebo Comparator: Placebo
2 single oral doses per subject
Drug: BI 10773 Placebo
2 times single dose
Active Comparator: Moxifloxacin
single oral dose per subject
Drug: Moxifloxacin
single oral dose

  Eligibility

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

Inclusion criteria:

healthy female and male subjects

  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: NCT01195675

Locations
Germany
1245.16.1 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

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01195675     History of Changes
Other Study ID Numbers: 1245.16, 2010-018609-13
Study First Received: September 3, 2010
Results First Received: May 16, 2014
Last Updated: July 25, 2014
Health Authority: Germany: BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte)
United States: Food and Drug Administration

Additional relevant MeSH terms:
Moxifloxacin
Norgestimate, ethinyl estradiol drug combination
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Contraceptives, Oral, Combined
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2014