Trial Outcomes & Findings for Assessment of the Effect of Empagliflozin (BI 10773) as Single Dose on the QT Interval in Healthy Female and Male Subjects (NCT NCT01195675)

NCT ID: NCT01195675

Last Updated: 2014-07-28

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 30 participants
• Primary outcome timeframe: 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
• Results posted on: 2014-07-28

Participant Flow

Participant milestones

Measure	Study Overall Total number of patients randomised and treated in the study. This was a randomised, placebo controlled, 5-period crossover trial, participants were randomised to one of ten possible treatment sequences. The treatments administered were * 25mg empa administered orally on day 1 of the treatment period * 200mg empa administered orally on day 1 of the treatment period * 400mg moxifloxacin administered orally on day 1 of the treatment period * Placebo 1 administered orally on day 1 of the treatment period * Placebo 2 administered orally on day 1 of the treatment period The trial was double-blind for the placebo and Empagliflozin (Empa) treatments, but open-label for the moxifloxacin treatment. A washout period of at least 1 week was respected between drug administrations.
Overall Study STARTED	30
Overall Study Received Empa 25mg	28
Overall Study Received Empa 200mg	30
Overall Study Received Moxifloxacin	29
Overall Study Received Placebo 1	29
Overall Study Received Placebo 2	28
Overall Study COMPLETED	27
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Measure	Study Overall Total number of patients randomised and treated in the study. This was a randomised, placebo controlled, 5-period crossover trial, participants were randomised to one of ten possible treatment sequences. The treatments administered were * 25mg empa administered orally on day 1 of the treatment period * 200mg empa administered orally on day 1 of the treatment period * 400mg moxifloxacin administered orally on day 1 of the treatment period * Placebo 1 administered orally on day 1 of the treatment period * Placebo 2 administered orally on day 1 of the treatment period The trial was double-blind for the placebo and Empagliflozin (Empa) treatments, but open-label for the moxifloxacin treatment. A washout period of at least 1 week was respected between drug administrations.
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Study Overall n=30 Participants Total number of patients randomised and treated in the study.
Age, Continuous	34.5 years STANDARD_DEVIATION 10.6 • n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

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.

Outcome measures

Measure	Placebo n=57 Observations Single oral dose of placebo (8 tablets).	Empa 25 mg n=28 Observations Single oral dose of Empagliflozin (Empa) 25mg (1 tablet with strength 25mg) plus 7 tablets of placebo.	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)
Empa 25mg: Mean QTcN Change From Baseline Between 1 and 4 Hours After Dosing	3.68 ms Standard Error 1.00	4.27 ms Standard Error 1.10	—	—

PRIMARY outcome

Timeframe: 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

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

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.

Outcome measures

Measure	Placebo n=57 Observations Single oral dose of placebo (8 tablets).	Empa 25 mg n=30 Observations Single oral dose of Empagliflozin (Empa) 25mg (1 tablet with strength 25mg) plus 7 tablets of placebo.	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)
Empa 200mg: Mean QTcN Change From Baseline Between 1 and 4 Hours After Dosing	3.67 ms Standard Deviation 0.86	3.44 ms Standard Deviation 0.94	—	—

SECONDARY outcome

Timeframe: 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

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

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.

Outcome measures

Measure	Placebo n=57 Observations Single oral dose of placebo (8 tablets).	Empa 25 mg n=28 Observations Single oral dose of Empagliflozin (Empa) 25mg (1 tablet with strength 25mg) plus 7 tablets of placebo.	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)
Empa 25 mg: Mean QTcN Change From Baseline Between 30 Minutes and 24 Hours After Dosing	0.71 ms Standard Error 0.99	1.37 ms Standard Error 1.06	—	—

SECONDARY outcome

Timeframe: 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

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

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.

Outcome measures

Measure	Placebo n=57 Observations Single oral dose of placebo (8 tablets).	Empa 25 mg n=30 Observations Single oral dose of Empagliflozin (Empa) 25mg (1 tablet with strength 25mg) plus 7 tablets of placebo.	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)
Empa 200 mg: Mean QTcN Change From Baseline Between 30 Minutes and 24 Hours After Dosing	0.68 ms Standard Deviation 0.80	0.53 ms Standard Deviation 0.87	—	—

SECONDARY outcome

Timeframe: 60 minutes (min), 50min and 40 min before the first dose and 2 hour (h), 2.5h, 3h and 4h after the first dose

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

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.

Outcome measures

Measure	Placebo n=57 Observations Single oral dose of placebo (8 tablets).	Empa 25 mg n=29 Observations Single oral dose of Empagliflozin (Empa) 25mg (1 tablet with strength 25mg) plus 7 tablets of placebo.	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)
Mean QTcN Change From Baseline Between 2 and 4 Hours After Dosing	3.53 ms Standard Error 1.10	15.96 ms Standard Error 1.24	—	—

SECONDARY outcome

Timeframe: 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

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

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.

Outcome measures

Measure	Placebo n=57 Observations Single oral dose of placebo (8 tablets).	Empa 25 mg n=28 Observations Single oral dose of Empagliflozin (Empa) 25mg (1 tablet with strength 25mg) plus 7 tablets of placebo.	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)
Empa 25mg: Change From Mean Baseline in QTcN at Each Time Point Between 30 Minutes and 24 Hours After Dosings	-4.46 ms Standard Error 0.96	-2.30 ms Standard Error 1.30	—	—

SECONDARY outcome

Timeframe: 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

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

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.

Outcome measures

Measure	Placebo n=57 Observations Single oral dose of placebo (8 tablets).	Empa 25 mg n=30 Observations Single oral dose of Empagliflozin (Empa) 25mg (1 tablet with strength 25mg) plus 7 tablets of placebo.	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)
Empa 200mg: Change From Mean Baseline in QTcN at Each Time Point Between 30 Minutes and 24 Hours After Dosings	3.05 ms Standard Error 0.96	4.64 ms Standard Error 1.15	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

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.

Outcome measures

Measure	Placebo n=28 Participants Single oral dose of placebo (8 tablets).	Empa 25 mg n=29 Participants Single oral dose of Empagliflozin (Empa) 25mg (1 tablet with strength 25mg) plus 7 tablets of placebo.	Moxifloxacin n=29 Participants Single oral dose of moxifloxacin 400 mg (1 tablet)	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)
Time-matched Change From Placebo in QTcN Between 30 Minutes and 24 Hours After Dosing.	4.05 ms Standard Deviation 5.62	3.45 ms Standard Deviation 10.18	13.99 ms Standard Deviation 8.19	—

OTHER_PRE_SPECIFIED outcome

Timeframe: 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

Population: Full analysis set (FAS): all treated subjects who had at least one baseline assessment and at least one post-baseline assessment for at least one ECG endpoint.

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.

Outcome measures

Measure	Placebo n=28 Participants Single oral dose of placebo (8 tablets).	Empa 25 mg n=29 Participants Single oral dose of Empagliflozin (Empa) 25mg (1 tablet with strength 25mg) plus 7 tablets of placebo.	Moxifloxacin n=29 Participants Single oral dose of moxifloxacin 400 mg (1 tablet)	Moxifloxacin Single oral dose of moxifloxacin 400 mg (1 tablet)
Placebo Corrected Change From Mean Baseline at Any Time Point Between 30 Minutes and 24 Hours After Dosings.	1.70 ms Standard Deviation 7.64	1.67 ms Standard Deviation 8.48	13.43 ms Standard Deviation 8.38	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Drug administration until beginning of next sequence/end of trial, up to 48 days

Population: Treated set (TS): All subjects who were dispensed trial medication and were documented to have taken at least one dose of investigational treatment.

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

Measure	Placebo n=29 Participants Single oral dose of placebo (8 tablets).	Empa 25 mg n=28 Participants Single oral dose of Empagliflozin (Empa) 25mg (1 tablet with strength 25mg) plus 7 tablets of placebo.	Moxifloxacin n=30 Participants Single oral dose of moxifloxacin 400 mg (1 tablet)	Moxifloxacin n=29 Participants Single oral dose of moxifloxacin 400 mg (1 tablet)
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator	0 participants	0 participants	0 participants	0 participants

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Empa 25 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Empa 200 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Moxifloxacin

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=29 participants at risk Single oral dose of placebo (8 tablets).	Empa 25 mg n=28 participants at risk Single oral dose of Empagliflozin (Empa) 25mg (1 tablet) plus 7 tablets of placebo.	Empa 200 mg n=30 participants at risk Single oral dose of Empagliflozin (Empa) 200 mg (8 tablets of 25 mg)	Moxifloxacin n=29 participants at risk Single oral dose of moxifloxacin 400 mg (1 tablet)
Injury, poisoning and procedural complications Road traffic accident	0.00% 0/29 • Drug administration until beginning of next sequence/end of trial, up to 48 days	0.00% 0/28 • Drug administration until beginning of next sequence/end of trial, up to 48 days	0.00% 0/30 • Drug administration until beginning of next sequence/end of trial, up to 48 days	3.4% 1/29 • Drug administration until beginning of next sequence/end of trial, up to 48 days

Other adverse events

Measure	Placebo n=29 participants at risk Single oral dose of placebo (8 tablets).	Empa 25 mg n=28 participants at risk Single oral dose of Empagliflozin (Empa) 25mg (1 tablet) plus 7 tablets of placebo.	Empa 200 mg n=30 participants at risk Single oral dose of Empagliflozin (Empa) 200 mg (8 tablets of 25 mg)	Moxifloxacin n=29 participants at risk Single oral dose of moxifloxacin 400 mg (1 tablet)
Infections and infestations Nasopharyngitis	17.2% 5/29 • Drug administration until beginning of next sequence/end of trial, up to 48 days	7.1% 2/28 • Drug administration until beginning of next sequence/end of trial, up to 48 days	6.7% 2/30 • Drug administration until beginning of next sequence/end of trial, up to 48 days	0.00% 0/29 • Drug administration until beginning of next sequence/end of trial, up to 48 days
Nervous system disorders Headache	6.9% 2/29 • Drug administration until beginning of next sequence/end of trial, up to 48 days	3.6% 1/28 • Drug administration until beginning of next sequence/end of trial, up to 48 days	0.00% 0/30 • Drug administration until beginning of next sequence/end of trial, up to 48 days	0.00% 0/29 • Drug administration until beginning of next sequence/end of trial, up to 48 days

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

Results disclosure agreements

• Principal investigator is a sponsor employee Other - Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
• Publication restrictions are in place

Restriction type: OTHER