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

A Phase 1, Randomized, Double-blind, Placebo- and Positive-controlled, 4-Period Crossover Trial to Assess the Effect of Anagrelide Hydrochloride on QT/QTc Interval in Healthy Men and Women.

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Anagrelide 0.5 mg; Drug: Anagrelide 2.5 mg; Drug: Moxifloxacin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Rueil-Malmaison, France
    • Biotrial

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; Anagrelide placebo + Moxifloxacin placebo single oral dose
ACTIVE_COMPARATOR: Moxifloxacin	Drug: Moxifloxacin; 400 mg Moxifloxacin single oral dose
EXPERIMENTAL: Anagrelide Therapeutic (0.5 mg)	Drug: Anagrelide 0.5 mg; 0.5mg Anagrelide single oral dose; Other Names: Agrylin, Xagrid
EXPERIMENTAL: Anagrelide Supratherapeutic (2.5 mg)	Drug: Anagrelide 2.5 mg; 2.5mg Anagrelide single oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.	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

Secondary Outcome Measures

Outcome Measure	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.	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

Collaborators and Investigators

• Sponsor: Shire

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 29, 2012
• Primary Completion (ACTUAL): July 25, 2012
• Study Completion (ACTUAL): July 25, 2012

Study Registration Dates

• First Submitted: March 6, 2012
• First Submitted That Met QC Criteria: March 9, 2012
• First Posted (ESTIMATE): March 13, 2012

Study Record Updates

• Last Update Posted (ACTUAL): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 24, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Moxifloxacin; Anagrelide
• Other Study ID Numbers: SPD422-111; 2011-005288-26 (EUDRACT_NUMBER)