Effect of Anagrelide Hydrochloride on Any Changes in Heart Function in Healthy Volunteers

Phase 1

Completed

Conditions: Healthy

Interventions: Drug: Anagrelide 0.5 mg
Drug: Anagrelide 2.5 mg
Drug: Placebo
Drug: Moxifloxacin

Registration Number: NCT01552928

Lead Sponsor: Shire

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Anagrelide Therapeutic (0.5 mg)	Anagrelide 0.5 mg	-
Anagrelide Supratherapeutic (2.5 mg)	Anagrelide 2.5 mg	-
Placebo	Placebo	-
Moxifloxacin	Moxifloxacin	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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.