Healthy
Conditions
Brief summary
According to the ICH Guidance Document E14, all non-antiarrhythmic drugs should be evaluated for their ability to prolong the QT interval which represents the duration of ventricular depolarization and subsequent repolarization. The primary objective of the study is to assess the effect of anagrelide on QT/QTc interval following a therapeutic and supratherapeutic dose of anagrelide when compared to placebo and a positive control.
Interventions
DRUGAnagrelide 0.5 mg
0.5mg Anagrelide single oral dose
DRUGAnagrelide 2.5 mg
2.5mg Anagrelide single oral dose
DRUGMoxifloxacin
400 mg Moxifloxacin single oral dose
DRUGPlacebo
Anagrelide placebo + Moxifloxacin placebo single oral dose
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18-45 years inclusive at the time of consent. The date of signing informed consent is defined as the beginning of the screening period. This inclusion criteria will only be assessed at the screening visit. * Subject is willing to comply with any applicable contraceptive requirements of the protocol and is: male, or non-pregnant non lactating female, or females must be at least 90 days post-partum or nulliparous. * Satisfactory medical assessment with no clinically or relevant abnormalities in medical history, physical examination, vital signs, ECG, and clinical laboratory evaluation as assessed by the investigator.
Exclusion criteria
* Current or recurrent disease that could affect the action, absorption, or disposition of the investigational product, or could affect clinical or laboratory assessments. a- Current or relevant history of physical or psychiatric illness, any medical disorder that may require treatment or make the subject unlikely to fully complete the study, or any condition that presents undue risk from the investigational product or procedures. * Significant illness, as judged by the Investigator, within 2 weeks of the first dose of investigational product.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals From Time-Matched Analysis by Largest Time Point | Over 12 hours post-dose | QT interval corrected for heart rate using the subject-specific method (QTcNi) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. The largest time point refers to the estimated largest mean difference between each treatment and placebo among all time points. Values for different treatments can come from different time points. |
| Mean Difference Changes From Baseline Versus Placebo in Heart Rate From Time-Matched Analysis by Largest Time Point | Over 12 hours post-dose | The largest time point refers to the estimated largest mean difference between each treatment and placebo among all time points. Values for different treatments can come from different time points. |
| Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals From Time-Matched Analysis by Largest Time Point | Over 12 hours post-dose | QT interval corrected for heart rate using Fridericia's method (QTcF) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. The largest time point refers to the estimated largest mean difference between each treatment and placebo among all time points. Values for different treatments can come from different time points. |
| Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals From Time-Matched Analysis by Largest Time Point | Over 12 hours post-dose | QT interval corrected for heart rate using Bazett's method (QTcB) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. The largest time point refers to the estimated largest mean difference between each treatment and placebo among all time points. Values for different treatments can come from different time points. |
| Mean Difference Changes From Baseline Versus Placebo in QT Intervals From Time-Matched Analysis by Largest Time Point | Over 12 hours post-dose | The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. The largest time point refers to the estimated largest mean difference between each treatment and placebo among all time points. Values for different treatments can come from different time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals at Subject-Specific Time of Maximum Plasma Concentration (Tmax) | Over 12 hours post-dose | QT interval corrected for heart rate using the subject-specific method (QTcNi) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. |
| Mean Difference Changes From Baseline Versus Placebo in Heart Rate at Subject-Specific Tmax | Over 12 hours post-dose | — |
| Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals at Subject-Specific Tmax | Over 12 hours post-dose | QT interval corrected for heart rate using Fridericia's method (QTcF) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. |
| Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals at Subject-Specific Tmax | Over 12 hours post-dose | QT interval corrected for heart rate using Bazett's method (QTcB) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. |
| Mean Difference Changes From Baseline Versus Placebo in QT Intervals at Subject-Specific Tmax | Over 12 hours post-dose | The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. |
| Maximum Plasma Concentration (Cmax) of 0.5 mg Anagrelide in Males and Females | Over 12 hours post-dose | — |
| Maximum Plasma Concentration (Cmax) of 2.5 mg Anagrelide in Males and Females | Over 12 hours post-dose | — |
| Maximum Plasma Concentration (Cmax) of Metabolite of 0.5 mg Anagrelide (BCH24426) in Males and Females | Over 12 hours post-dose | — |
| Maximum Plasma Concentration (Cmax) of Metabolite of 2.5 mg Anagrelide (BCH24426) in Males and Females | Over 12 hours post-dose | — |
Countries
France
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Anag 0.5 mg, Then Anag 2.5 mg, Then Placebo, Then Mox 400 mg A single oral dose of 0.5 mg of anagrelide on Day 1 for Period 1; then a single oral dose of 2.5 mg of anagrelide on Day 1 for Period 2; then a single oral dose of placebo on Day 1 for Period 3; then a single oral dose of 400 mg of moxifloxacin on Day 1 for Period 4. | 14 |
| Anag 2.5 mg, Then Mox 400 mg, Then Anag 0.5 mg, Then Placebo A single oral dose of 2.5 mg of anagrelide on Day 1 for Period 1; then a single oral dose of 400 mg of moxifloxacin on Day 1 for Period 2; then a single oral dose of 0.5 mg of anagrelide on Day 1 for Period 3; then a single oral dose of placebo on Day 1 for Period 4. | 15 |
| Mox 400 mg, Then Placebo, Then Anag 2.5 mg, Then Anag 0.5 mg A single oral dose of 400 mg of moxifloxacin on Day 1 for Period 1; then a single oral dose of placebo on Day 1 for Period 2; then a single oral dose of 2.5 mg of anagrelide on Day 1 for Period 3; then a single oral dose of 0.5 mg of anagrelide on Day 1 for Period 4. | 15 |
| Placebo, Then Anag 0.5 mg, Then Mox 400 mg, Then Anag 2.5 mg A single oral dose of placebo on Day 1 for Period 1; then a single oral dose of 0.5 mg of anagrelide on Day 1 for Period 2; then a single oral dose of 400 mg of moxifloxacin on Day 1 for Period 3; then a single oral dose of 2.5 mg of anagrelide on Day 1 for Period 4. | 16 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period 3 | Adverse Event | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Anag 2.5 mg, Then Mox 400 mg, Then Anag 0.5 mg, Then Placebo | Mox 400 mg, Then Placebo, Then Anag 2.5 mg, Then Anag 0.5 mg | Anag 0.5 mg, Then Anag 2.5 mg, Then Placebo, Then Mox 400 mg | Placebo, Then Anag 0.5 mg, Then Mox 400 mg, Then Anag 2.5 mg | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 15 Participants | 14 Participants | 16 Participants | 60 Participants |
| Age, Continuous | 28.4 Years STANDARD_DEVIATION 7.7 | 29.5 Years STANDARD_DEVIATION 5.83 | 28.1 Years STANDARD_DEVIATION 6.44 | 30.4 Years STANDARD_DEVIATION 8.02 | 29.2 Years STANDARD_DEVIATION 6.96 |
| Region of Enrollment FRANCE | 15 Participants | 15 Participants | 14 Participants | 16 Participants | 60 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 6 Participants | 7 Participants | 25 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 8 Participants | 9 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 59 | 49 / 60 | 2 / 60 | 0 / 60 |
| serious Total, serious adverse events | 0 / 59 | 0 / 60 | 0 / 60 | 0 / 60 |
Outcome results
Primary
Mean Difference Changes From Baseline Versus Placebo in Heart Rate From Time-Matched Analysis by Largest Time Point
The largest time point refers to the estimated largest mean difference between each treatment and placebo among all time points. Values for different treatments can come from different time points.
Time frame: Over 12 hours post-dose
Population: Full Analysis Set (FAS) consists of subjects in the Safety Analysis Set who had at least 1 electrocardiogram (ECG). Safety Analysis Set consists of subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Anagrelide 0.5 mg | Mean Difference Changes From Baseline Versus Placebo in Heart Rate From Time-Matched Analysis by Largest Time Point | 7.8 beats per minute |
| Anagrelide 2.5 mg | Mean Difference Changes From Baseline Versus Placebo in Heart Rate From Time-Matched Analysis by Largest Time Point | 29.1 beats per minute |
| Moxifloxacin 400 mg | Mean Difference Changes From Baseline Versus Placebo in Heart Rate From Time-Matched Analysis by Largest Time Point | 4.3 beats per minute |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.004ANCOVA
Primary
Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals From Time-Matched Analysis by Largest Time Point
QT interval corrected for heart rate using Bazett's method (QTcB) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. The largest time point refers to the estimated largest mean difference between each treatment and placebo among all time points. Values for different treatments can come from different time points.
Time frame: Over 12 hours post-dose
Population: Full Analysis Set (FAS) consists of subjects in the Safety Analysis Set who had at least 1 electrocardiogram (ECG). Safety Analysis Set consists of subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Anagrelide 0.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals From Time-Matched Analysis by Largest Time Point | -2.9 msec |
| Anagrelide 2.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals From Time-Matched Analysis by Largest Time Point | -18.1 msec |
| Moxifloxacin 400 mg | Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals From Time-Matched Analysis by Largest Time Point | -2.3 msec |
p-value: 0.078ANCOVA
p-value: <0.001ANCOVA
p-value: 0.156ANCOVA
Primary
Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals From Time-Matched Analysis by Largest Time Point
QT interval corrected for heart rate using Fridericia's method (QTcF) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. The largest time point refers to the estimated largest mean difference between each treatment and placebo among all time points. Values for different treatments can come from different time points.
Time frame: Over 12 hours post-dose
Population: Full Analysis Set (FAS) consists of subjects in the Safety Analysis Set who had at least 1 electrocardiogram (ECG). Safety Analysis Set consists of subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Anagrelide 0.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals From Time-Matched Analysis by Largest Time Point | 5.0 msec |
| Anagrelide 2.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals From Time-Matched Analysis by Largest Time Point | 10.0 msec |
| Moxifloxacin 400 mg | Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals From Time-Matched Analysis by Largest Time Point | 11.8 msec |
p-value: 0.005ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Primary
Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals From Time-Matched Analysis by Largest Time Point
QT interval corrected for heart rate using the subject-specific method (QTcNi) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. The largest time point refers to the estimated largest mean difference between each treatment and placebo among all time points. Values for different treatments can come from different time points.
Time frame: Over 12 hours post-dose
Population: Full Analysis Set (FAS) consists of subjects in the Safety Analysis Set who had at least 1 electrocardiogram (ECG). Safety Analysis Set consists of subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Anagrelide 0.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals From Time-Matched Analysis by Largest Time Point | 7.0 msec |
| Anagrelide 2.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals From Time-Matched Analysis by Largest Time Point | 13.0 msec |
| Moxifloxacin 400 mg | Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals From Time-Matched Analysis by Largest Time Point | 12.6 msec |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Primary
Mean Difference Changes From Baseline Versus Placebo in QT Intervals From Time-Matched Analysis by Largest Time Point
The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value. The largest time point refers to the estimated largest mean difference between each treatment and placebo among all time points. Values for different treatments can come from different time points.
Time frame: Over 12 hours post-dose
Population: Full Analysis Set (FAS) consists of subjects in the Safety Analysis Set who had at least 1 electrocardiogram (ECG). Safety Analysis Set consists of subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Anagrelide 0.5 mg | Mean Difference Changes From Baseline Versus Placebo in QT Intervals From Time-Matched Analysis by Largest Time Point | 1.7 msec |
| Anagrelide 2.5 mg | Mean Difference Changes From Baseline Versus Placebo in QT Intervals From Time-Matched Analysis by Largest Time Point | -2.4 msec |
| Moxifloxacin 400 mg | Mean Difference Changes From Baseline Versus Placebo in QT Intervals From Time-Matched Analysis by Largest Time Point | 9.6 msec |
p-value: 0.439ANCOVA
p-value: 0.274ANCOVA
p-value: <0.001ANCOVA
Secondary
Maximum Plasma Concentration (Cmax) of 0.5 mg Anagrelide in Males and Females
Time frame: Over 12 hours post-dose
Population: Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set who had evaluable concentration-time profiles for anagrelide, BCH24426, or moxifloxacin.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Anagrelide 0.5 mg | Maximum Plasma Concentration (Cmax) of 0.5 mg Anagrelide in Males and Females | 2.083 ng/ml | Standard Deviation 0.975 |
| Anagrelide 2.5 mg | Maximum Plasma Concentration (Cmax) of 0.5 mg Anagrelide in Males and Females | 3.64 ng/ml | Standard Deviation 1.959 |
Secondary
Maximum Plasma Concentration (Cmax) of 2.5 mg Anagrelide in Males and Females
Time frame: Over 12 hours post-dose
Population: Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set who had evaluable concentration-time profiles for anagrelide, BCH24426, or moxifloxacin.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Anagrelide 0.5 mg | Maximum Plasma Concentration (Cmax) of 2.5 mg Anagrelide in Males and Females | 10.592 ng/ml | Standard Deviation 4.871 |
| Anagrelide 2.5 mg | Maximum Plasma Concentration (Cmax) of 2.5 mg Anagrelide in Males and Females | 16.378 ng/ml | Standard Deviation 10.224 |
Secondary
Maximum Plasma Concentration (Cmax) of Metabolite of 0.5 mg Anagrelide (BCH24426) in Males and Females
Time frame: Over 12 hours post-dose
Population: Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set who had evaluable concentration-time profiles for anagrelide, BCH24426, or moxifloxacin.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Anagrelide 0.5 mg | Maximum Plasma Concentration (Cmax) of Metabolite of 0.5 mg Anagrelide (BCH24426) in Males and Females | 3.731 ng/ml | Standard Deviation 1.257 |
| Anagrelide 2.5 mg | Maximum Plasma Concentration (Cmax) of Metabolite of 0.5 mg Anagrelide (BCH24426) in Males and Females | 4.534 ng/ml | Standard Deviation 1.405 |
Secondary
Maximum Plasma Concentration (Cmax) of Metabolite of 2.5 mg Anagrelide (BCH24426) in Males and Females
Time frame: Over 12 hours post-dose
Population: Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set who had evaluable concentration-time profiles for anagrelide, BCH24426, or moxifloxacin.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Anagrelide 0.5 mg | Maximum Plasma Concentration (Cmax) of Metabolite of 2.5 mg Anagrelide (BCH24426) in Males and Females | 18.927 ng/ml | Standard Deviation 6.016 |
| Anagrelide 2.5 mg | Maximum Plasma Concentration (Cmax) of Metabolite of 2.5 mg Anagrelide (BCH24426) in Males and Females | 23.785 ng/ml | Standard Deviation 7.952 |
Secondary
Mean Difference Changes From Baseline Versus Placebo in Heart Rate at Subject-Specific Tmax
Time frame: Over 12 hours post-dose
Population: Full Analysis Set (FAS) consists of subjects in the Safety Analysis Set who had at least 1 electrocardiogram (ECG). Safety Analysis Set consists of subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Anagrelide 0.5 mg | Mean Difference Changes From Baseline Versus Placebo in Heart Rate at Subject-Specific Tmax | 4.5 beats per minute |
| Anagrelide 2.5 mg | Mean Difference Changes From Baseline Versus Placebo in Heart Rate at Subject-Specific Tmax | 21.8 beats per minute |
| Moxifloxacin 400 mg | Mean Difference Changes From Baseline Versus Placebo in Heart Rate at Subject-Specific Tmax | 2.9 beats per minute |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: 0.001ANCOVA
Secondary
Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals at Subject-Specific Tmax
QT interval corrected for heart rate using Bazett's method (QTcB) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value.
Time frame: Over 12 hours post-dose
Population: Full Analysis Set (FAS) consists of subjects in the Safety Analysis Set who had at least 1 electrocardiogram (ECG). Safety Analysis Set consists of subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Anagrelide 0.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals at Subject-Specific Tmax | 8.5 msec |
| Anagrelide 2.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals at Subject-Specific Tmax | 25.5 msec |
| Moxifloxacin 400 mg | Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals at Subject-Specific Tmax | 14.0 msec |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals at Subject-Specific Tmax
QT interval corrected for heart rate using Fridericia's method (QTcF) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value.
Time frame: Over 12 hours post-dose
Population: Full Analysis Set (FAS) consists of subjects in the Safety Analysis Set who had at least 1 electrocardiogram (ECG). Safety Analysis Set consists of subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Anagrelide 0.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals at Subject-Specific Tmax | 3.7 msec |
| Anagrelide 2.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals at Subject-Specific Tmax | 4.5 msec |
| Moxifloxacin 400 mg | Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals at Subject-Specific Tmax | 10.8 msec |
p-value: 0.012ANCOVA
p-value: 0.044ANCOVA
p-value: <0.001ANCOVA
Secondary
Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals at Subject-Specific Time of Maximum Plasma Concentration (Tmax)
QT interval corrected for heart rate using the subject-specific method (QTcNi) at the subject-specific time of maximum plasma concentration. The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value.
Time frame: Over 12 hours post-dose
Population: Full Analysis Set (FAS) consists of subjects in the Safety Analysis Set who had at least 1 electrocardiogram (ECG). Safety Analysis Set consists of subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Anagrelide 0.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals at Subject-Specific Time of Maximum Plasma Concentration (Tmax) | 4.4 msec |
| Anagrelide 2.5 mg | Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals at Subject-Specific Time of Maximum Plasma Concentration (Tmax) | 8.2 msec |
| Moxifloxacin 400 mg | Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals at Subject-Specific Time of Maximum Plasma Concentration (Tmax) | 11.3 msec |
p-value: 0.004ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Mean Difference Changes From Baseline Versus Placebo in QT Intervals at Subject-Specific Tmax
The QT interval is the time it takes for the ventricles of the heart to contract and relax. Data were subtracted from the placebo value.
Time frame: Over 12 hours post-dose
Population: Full Analysis Set (FAS) consists of subjects in the Safety Analysis Set who had at least 1 electrocardiogram (ECG). Safety Analysis Set consists of subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Anagrelide 0.5 mg | Mean Difference Changes From Baseline Versus Placebo in QT Intervals at Subject-Specific Tmax | -6.1 msec |
| Anagrelide 2.5 mg | Mean Difference Changes From Baseline Versus Placebo in QT Intervals at Subject-Specific Tmax | -34.3 msec |
| Moxifloxacin 400 mg | Mean Difference Changes From Baseline Versus Placebo in QT Intervals at Subject-Specific Tmax | 4.3 msec |
p-value: 0.003ANCOVA
p-value: <0.001ANCOVA
p-value: 0.043ANCOVA