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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-005288-26 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anagrelide Therapeutic (0.5 mg) | Experimental |
| |
| Anagrelide Supratherapeutic (2.5 mg) | Experimental |
| |
| Moxifloxacin | Active Comparator |
| |
| Placebo | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Anagrelide 0.5 mg | Drug | 0.5mg Anagrelide single oral dose |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Over 12 hours post-dose |
| 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. | Over 12 hours post-dose |
| 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. | Over 12 hours post-dose |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
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.
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| Name | Affiliation | Role |
|---|---|---|
| Study Director | Takeda | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biotrial | Rueil-Malmaison | France |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| FG003 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
| |||||||||||||
| Period 2 |
| |||||||||||||
| Period 3 |
| |||||||||||||
| Period 4 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Over 12 hours post-dose |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Anagrelide 0.5mg |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Shire | +1 866 842 5335 | ClinicalTransparency@shire.com |
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| ID | Term |
|---|---|
| C021139 | anagrelide |
| D000077266 | Moxifloxacin |
| ID | Term |
|---|---|
| D024841 | Fluoroquinolones |
| D042462 | 4-Quinolones |
| D015363 | Quinolones |
| D011804 | Quinolines |
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| Anagrelide 2.5 mg | Drug | 2.5mg Anagrelide single oral dose |
|
| Moxifloxacin | Drug | 400 mg Moxifloxacin single oral dose |
|
| Placebo | Drug | Anagrelide placebo + Moxifloxacin placebo single oral dose |
|
| Over 12 hours post-dose |
| 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. | Over 12 hours post-dose |
| Over 12 hours post-dose |
| 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 | 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. | Over 12 hours post-dose |
| 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. | Over 12 hours post-dose |
| 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. | Over 12 hours post-dose |
| 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 |
| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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|
| COMPLETED |
|
| NOT COMPLETED |
|
| 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. |
| BG002 | 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. |
| BG003 | 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. |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Anagrelide 2.5 mg | A single oral dose of 2.5 mg of anagrelide |
| OG002 | Moxifloxacin 400 mg | A single oral dose of 400 mg of moxifloxacin |
|
|
|
| Secondary | Mean Difference Changes From Baseline Versus Placebo in Heart Rate at Subject-Specific Tmax | 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. | Posted | Least Squares Mean | 90% Confidence Interval | beats per minute | Over 12 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Over 12 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Over 12 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Over 12 hours post-dose |
|
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) of 0.5 mg Anagrelide in Males and Females | Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set who had evaluable concentration-time profiles for anagrelide, BCH24426, or moxifloxacin. | Posted | Geometric Mean | Standard Deviation | ng/ml | Over 12 hours post-dose |
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) of 2.5 mg Anagrelide in Males and Females | Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set who had evaluable concentration-time profiles for anagrelide, BCH24426, or moxifloxacin. | Posted | Geometric Mean | Standard Deviation | ng/ml | Over 12 hours post-dose |
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) of Metabolite of 0.5 mg Anagrelide (BCH24426) in Males and Females | Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set who had evaluable concentration-time profiles for anagrelide, BCH24426, or moxifloxacin. | Posted | Geometric Mean | Standard Deviation | ng/ml | Over 12 hours post-dose |
|
|
|
| Secondary | Maximum Plasma Concentration (Cmax) of Metabolite of 2.5 mg Anagrelide (BCH24426) in Males and Females | Pharmacokinetic Analysis Set consists of all subjects in the Safety Analysis Set who had evaluable concentration-time profiles for anagrelide, BCH24426, or moxifloxacin. | Posted | Geometric Mean | Standard Deviation | ng/ml | Over 12 hours post-dose |
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Over 12 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | beats per minute | Over 12 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Over 12 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Over 12 hours post-dose |
|
|
|
|
| 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. | 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. | Posted | Least Squares Mean | 90% Confidence Interval | msec | Over 12 hours post-dose |
|
|
|
|
| 0 |
| 59 |
| 13 |
| 59 |
| EG001 | Anagrelide 2.5mg | 0 | 60 | 49 | 60 |
| EG002 | Moxifloxacin 400mg | 0 | 60 | 2 | 60 |
| EG003 | Placebo | 0 | 60 | 0 | 60 |
| Constipation | Gastrointestinal disorders |
|
| Nausea | Gastrointestinal disorders |
|
| Vomiting | Gastrointestinal disorders |
|
| Dizziness | Nervous system disorders |
|
| Headache | Nervous system disorders |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders |
|
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| Superiority or Other (legacy) |
| ANCOVA | 0.001 | Superiority or Other (legacy) |
| Superiority or Other (legacy) |
| ANCOVA | <0.001 | Superiority or Other (legacy) |
| Superiority or Other (legacy) |
| ANCOVA | <0.001 | Superiority or Other (legacy) |
| Superiority or Other (legacy) |
| ANCOVA | 0.043 | Superiority or Other (legacy) |
| Superiority or Other (legacy) |
| ANCOVA | <0.001 | Superiority or Other (legacy) |
| Superiority or Other (legacy) |
| ANCOVA | 0.004 | Superiority or Other (legacy) |
| Superiority or Other (legacy) |
| ANCOVA | <0.001 | Superiority or Other (legacy) |
| Superiority or Other (legacy) |
| ANCOVA | 0.156 | Superiority or Other (legacy) |
| Superiority or Other (legacy) |
| ANCOVA | <0.001 | Superiority or Other (legacy) |