Trial Outcomes & Findings for Food and Insulin Effect on QT/QTC Interval of ECG (NCT NCT01642485)
NCT ID: NCT01642485
Last Updated: 2014-08-20
Results Overview
The primary baseline corrections were calculated using averaged QTc baseline values (the mean of all median readings recorded for each time-point on the baseline Day -1). This single value (QTcbaselineAV) was used to calculate ΔQTc for each study period.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4 and 6 hours post-dose
Results posted on
2014-08-20
Participant Flow
Participant milestones
| Measure |
Sequence 1
Period1:
Day 1: Placebo Day 2: Insulin Clamp Day 3: Moxiloxacin 400 mg fasted Washout period: 3 days
Period 2:
Day 1: Continental breakfast Day 2:FDA breakfast Day 3: Moxifloxacin 400 mg fed (with continental breakfast)
|
Sequence 2
Period1:
Day 1: Insulin Clamp Day 2: Continental breakfast Day 3: Moxiloxacin 400 mg fasted Washout period: 3 days
Period 2:
Day 1: FDA breakfast Day 2: Placebo Day 3: Moxifloxacin 400 mg fed (with continental breakfast)
|
Sequence 3
Period1:
Day 1: Continental breakfast Day 2: FDA breakfast Day 3: Moxiloxacin 400 mg fasted Washout period: 3 days
Period 2:
Day 1: Placebo Day 2: Insulin Clamp Day 3: Moxifloxacin 400 mg fed (with continental breakfast)
|
Sequence 4
Period1:
Day 1: FDA breakfast Day 2: Placebo Day 3: Moxiloxacin 400 mg fasted Washout period: 3 days
Period 2:
Day 1: Insulin Clamp Day 2: Continental breakfast Day 3: Moxifloxacin 400 mg fed (with continental breakfast)
|
Sequence 5
Period1:
Day 1: Placebo Day 2: Insulin Clamp Day 3: Moxiloxacin 400 mg fed (with continental breakfast) Washout period: 3 days
Period 2:
Day 1: Continental breakfast Day 2:FDA breakfast Day 3: Moxifloxacin 400 mg fasted
|
Sequence 6
Period1:
Day 1: Insulin Clamp Day 2: Continental breakfast Day 3: Moxiloxacin 400 mg fed (with continental breakfast) Washout period: 3 days
Period 2:
Day 1: FDA breakfast Day 2: Placebo Day 3: Moxifloxacin 400 mg fasted
|
Sequence 7
Period1:
Day 1: Continental breakfast Day 2: FDA breakfast Day 3: Moxiloxacin 400 mg fed (with continental breakfast) Washout period: 3 days
Period 2:
Day 1: Placebo Day 2: Insulin Clamp Day 3: Moxifloxacin 400 mg fasted
|
Sequence 8
Period1:
Day 1: FDA breakfast Day 2: Placebo Day 3: Moxiloxacin 400 mg fed (with continental breakfast) Washout period: 3 days
Period 2:
Day 1: Insulin Clamp Day 2: Continental breakfast Day 3: Moxifloxacin 400 mg fasted
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Period 1, Day 1
STARTED
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4
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4
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4
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4
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4
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4
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4
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4
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Period 1, Day 1
COMPLETED
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4
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4
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4
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4
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4
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4
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Period 1, Day 1
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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Period 1, Day 2
STARTED
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4
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Period 1, Day 2
COMPLETED
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4
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Period 1, Day 2
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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Period 1, Day 3
STARTED
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4
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4
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4
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4
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Period 1, Day 3
COMPLETED
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4
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4
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4
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4
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4
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4
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4
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4
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Period 1, Day 3
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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Period 2, Day 1
STARTED
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4
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4
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4
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Period 2, Day 1
COMPLETED
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4
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4
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4
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4
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4
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4
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4
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Period 2, Day 1
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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Period 2, Day 2
STARTED
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4
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4
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4
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4
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4
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4
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4
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4
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Period 2, Day 2
COMPLETED
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4
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4
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4
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4
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4
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4
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4
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4
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Period 2, Day 2
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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Period 2, Day 3
STARTED
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4
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4
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4
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4
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4
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4
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4
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4
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Period 2, Day 3
COMPLETED
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4
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4
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4
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4
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4
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4
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4
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4
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Period 2, Day 3
NOT COMPLETED
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0
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0
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0
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0
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0
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0
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0
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Food and Insulin Effect on QT/QTC Interval of ECG
Baseline characteristics by cohort
| Measure |
All Study Participants
n=32 Participants
Subjects participating in the study attended for screening, two treatment periods (periods 1 and 2) of 4 assessment days each and a follow-up visit. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in fasted condition or with Continental breakfast, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. No wash-out was required between the other treatments investigated. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
|---|---|
|
Age, Continuous
Caucasian
|
25.6 years
STANDARD_DEVIATION 4.7 • n=5 Participants
|
|
Age, Continuous
Japanese
|
27.6 years
STANDARD_DEVIATION 3.3 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
13 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
19 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
32 participants
n=5 Participants
|
|
Body Mass Index
>18 kg/m^2
|
32 participants
n=5 Participants
|
|
Body Mass Index
>25 kg/m^2
|
0 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4 and 6 hours post-dosePopulation: Since the baseline was used as a covariate in the analysis, using the standard deviation of the change from baseline, in the simple sample size formula is justified. Assuming a standard deviation of 7 msec for the single differences, sample sizes for the sum can therefore work with a standard deviation of 6.5 msec.
The primary baseline corrections were calculated using averaged QTc baseline values (the mean of all median readings recorded for each time-point on the baseline Day -1). This single value (QTcbaselineAV) was used to calculate ΔQTc for each study period.
Outcome measures
| Measure |
Fasted Group
n=32 Participants
This study was designed as an open-label, randomized, placebo-controlled, crossover trial that evaluated the effect of a 400 mg oral dose of moxifloxacin in fasted conditions to a baseline and a placebo treatment. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in either the fed or fasted condition, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
Fed Group
n=32 Participants
This study was designed as an open-label, randomized, placebo-controlled, crossover trial that evaluated the effect of a 400 mg oral dose of moxifloxacin in fed conditions to a baseline and a placebo treatment. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in either the fed or fasted condition, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
Placebo at Baseline
a baseline QTcF measured on Day -1 of each period
|
Japanese Fed Group
The results of concentration-effect analysis: the effect of moxifloxacin on QTcF (double difference of QTcF) at the time point of maximum mean concentrationof moxifloxacin (4h)
|
|---|---|---|---|---|
|
The Effect of Food (Fasted and Fed State) on the Degree of QT Prolongation Caused by Moxifloxacin
|
14.4 ms
Interval 11.9 to 16.8
|
11.6 ms
Interval 9.1 to 14.1
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4 and 6 hours post-doseScott et al (2002) demonstrated an increase in the heart rate of 10bpm in some healthy subjects following ingestion of a carbohydrate meal. There was significant correlation between the resultant hyperinsulinaemia and an increase in skeletal muscle blood flow, and sympathetic activity, with a reduction in vascular resistance. If postprandial insulinaemia is a significant influence on the QT interval, then carbohydrate rich meals would be expected to show greater effect. Therefore, to explore this on two separate days of the study subjects will be given one of two different types of breakfast: 1. A high carbohydrate content breakfast, (\>70% carbohydrate) 2. A reduced calorie FDA standard breakfast, (58% fat, low carbohydrate content) to determine effect on QT interval.
Outcome measures
| Measure |
Fasted Group
n=32 Participants
This study was designed as an open-label, randomized, placebo-controlled, crossover trial that evaluated the effect of a 400 mg oral dose of moxifloxacin in fasted conditions to a baseline and a placebo treatment. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in either the fed or fasted condition, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
Fed Group
n=32 Participants
This study was designed as an open-label, randomized, placebo-controlled, crossover trial that evaluated the effect of a 400 mg oral dose of moxifloxacin in fed conditions to a baseline and a placebo treatment. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in either the fed or fasted condition, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
Placebo at Baseline
n=32 Participants
a baseline QTcF measured on Day -1 of each period
|
Japanese Fed Group
The results of concentration-effect analysis: the effect of moxifloxacin on QTcF (double difference of QTcF) at the time point of maximum mean concentrationof moxifloxacin (4h)
|
|---|---|---|---|---|
|
The Food Effects (Calorie Reduced FDA Breakfast and Carbohydrate Rich Continental Style) on QTcF
|
-6.8 ms
Interval -9.3 to -4.3
|
-7.9 ms
Interval -10.4 to -5.5
|
412.4 ms
Interval 407.9 to 416.9
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4 and 6 hours post-dose"Moxifloxacin 400mg Fasted" group is reporting the maximum change in QT/QTc interval from placebo treatment.
Outcome measures
| Measure |
Fasted Group
n=32 Participants
This study was designed as an open-label, randomized, placebo-controlled, crossover trial that evaluated the effect of a 400 mg oral dose of moxifloxacin in fasted conditions to a baseline and a placebo treatment. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in either the fed or fasted condition, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
Fed Group
n=32 Participants
This study was designed as an open-label, randomized, placebo-controlled, crossover trial that evaluated the effect of a 400 mg oral dose of moxifloxacin in fed conditions to a baseline and a placebo treatment. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in either the fed or fasted condition, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
Placebo at Baseline
a baseline QTcF measured on Day -1 of each period
|
Japanese Fed Group
The results of concentration-effect analysis: the effect of moxifloxacin on QTcF (double difference of QTcF) at the time point of maximum mean concentrationof moxifloxacin (4h)
|
|---|---|---|---|---|
|
Moxifloxacin 400 mg (Single Dose) Compared to Placebo on the Mean QT/QTc Interval.
|
14.4 ms
Interval 11.9 to 16.8
|
414.2 ms
Interval 409.6 to 418.8
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4 and 6 hours post-doseThe effect on QTc was investigated using linear mixed effect models with placebo corrected QTcF (change from average baseline) as a dependent variable and insulin, glucose and C-peptide (placebo corrected) as covariates for the data obtained under the euglycaemic clamp as well as for all data obtained under the clamp and the two types of breakfast.
Outcome measures
| Measure |
Fasted Group
n=32 Participants
This study was designed as an open-label, randomized, placebo-controlled, crossover trial that evaluated the effect of a 400 mg oral dose of moxifloxacin in fasted conditions to a baseline and a placebo treatment. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in either the fed or fasted condition, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
Fed Group
n=32 Participants
This study was designed as an open-label, randomized, placebo-controlled, crossover trial that evaluated the effect of a 400 mg oral dose of moxifloxacin in fed conditions to a baseline and a placebo treatment. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in either the fed or fasted condition, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
Placebo at Baseline
n=32 Participants
a baseline QTcF measured on Day -1 of each period
|
Japanese Fed Group
The results of concentration-effect analysis: the effect of moxifloxacin on QTcF (double difference of QTcF) at the time point of maximum mean concentrationof moxifloxacin (4h)
|
|---|---|---|---|---|
|
Insulin, Glucose and C-Peptide Effects on the QT/QTc Interval
|
-0.01 msec
Interval -0.02 to 0.04
|
-0.86 msec
Interval -1.45 to -0.27
|
-0.71 msec
Interval -0.98 to -0.45
|
—
|
SECONDARY outcome
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4 and 6 hours post-doseOutcome measures
| Measure |
Fasted Group
n=13 Participants
This study was designed as an open-label, randomized, placebo-controlled, crossover trial that evaluated the effect of a 400 mg oral dose of moxifloxacin in fasted conditions to a baseline and a placebo treatment. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in either the fed or fasted condition, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
Fed Group
n=13 Participants
This study was designed as an open-label, randomized, placebo-controlled, crossover trial that evaluated the effect of a 400 mg oral dose of moxifloxacin in fed conditions to a baseline and a placebo treatment. Data obtained on study days 1 and 2 compared the ECG effects of different types of food and placebo. Each period consisted of a baseline ECG day (day -1) and treatment days (days 1-3). Moxifloxacin was given in either the fed or fasted condition, on day 3 of each study period. The two periods were separated by at least 3 days to allow for the effects of moxifloxacin to wash-out. The ECG and samples for PK and PD analysis on the treatment days were taken at the corresponding clock time points as on the baseline days. Each subject received all treatments and all the comparisons between treatment effects were made intra-individually reducing the anticipated variability and thereby reducing the sample size.
|
Placebo at Baseline
n=19 Participants
a baseline QTcF measured on Day -1 of each period
|
Japanese Fed Group
n=19 Participants
The results of concentration-effect analysis: the effect of moxifloxacin on QTcF (double difference of QTcF) at the time point of maximum mean concentrationof moxifloxacin (4h)
|
|---|---|---|---|---|
|
The QTcF Profile of Oral Moxifloxacin (400 mg) in Healthy Japanese Versus Caucasian Subjects
|
9.0 ms
Interval 3.2 to 14.7
|
13.7 ms
Interval 8.2 to 19.2
|
17.3 ms
Interval 13.9 to 20.6
|
10.1 ms
Interval 5.1 to 15.1
|
Adverse Events
Moxifloxacin 400 mg Fasted
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Moxifloxacin 400 mg Fed
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place