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

• ClinicalTrials.gov Identifier: NCT01552928
• Recruitment Status: Completed
• First Posted: March 13, 2012
• Results First Posted: January 10, 2014
• Last Update Posted: June 9, 2021
• Sponsor: Shire
• Information provided by (Responsible Party): Takeda ( Shire )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Anagrelide 0.5 mg; Drug: Anagrelide 2.5 mg; Drug: Moxifloxacin; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: March 29, 2012
• Actual Primary Completion Date: July 25, 2012
• Actual Study Completion Date: July 25, 2012

Arms and Interventions

Arm	Intervention/treatment
Experimental: Anagrelide Therapeutic (0.5 mg)	Drug: Anagrelide 0.5 mg; 0.5mg Anagrelide single oral dose; Other Name: Agrylin, Xagrid
Experimental: Anagrelide Supratherapeutic (2.5 mg)	Drug: Anagrelide 2.5 mg; 2.5mg Anagrelide single oral dose
Active Comparator: Moxifloxacin	Drug: Moxifloxacin; 400 mg Moxifloxacin single oral dose
Placebo Comparator: Placebo	Drug: Placebo; Anagrelide placebo + Moxifloxacin placebo single oral dose

Outcome Measures

Primary Outcome Measures :

1. Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals From Time-Matched Analysis by Largest Time Point [ Time Frame: 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.
2. Mean Difference Changes From Baseline Versus Placebo in Heart Rate From Time-Matched Analysis by Largest Time Point [ Time Frame: 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.
3. Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals From Time-Matched Analysis by Largest Time Point [ Time Frame: 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.
4. Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals From Time-Matched Analysis by Largest Time Point [ Time Frame: 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.
5. Mean Difference Changes From Baseline Versus Placebo in QT Intervals From Time-Matched Analysis by Largest Time Point [ Time Frame: 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 :

1. Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals at Subject-Specific Time of Maximum Plasma Concentration (Tmax) [ Time Frame: 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.
2. Mean Difference Changes From Baseline Versus Placebo in Heart Rate at Subject-Specific Tmax [ Time Frame: Over 12 hours post-dose ]
3. Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals at Subject-Specific Tmax [ Time Frame: 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.
4. Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals at Subject-Specific Tmax [ Time Frame: 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.
5. Mean Difference Changes From Baseline Versus Placebo in QT Intervals at Subject-Specific Tmax [ Time Frame: 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.
6. Maximum Plasma Concentration (Cmax) of 0.5 mg Anagrelide in Males and Females [ Time Frame: Over 12 hours post-dose ]
7. Maximum Plasma Concentration (Cmax) of 2.5 mg Anagrelide in Males and Females [ Time Frame: Over 12 hours post-dose ]
8. Maximum Plasma Concentration (Cmax) of Metabolite of 0.5 mg Anagrelide (BCH24426) in Males and Females [ Time Frame: Over 12 hours post-dose ]
9. Maximum Plasma Concentration (Cmax) of Metabolite of 2.5 mg Anagrelide (BCH24426) in Males and Females [ Time Frame: Over 12 hours post-dose ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

France

Biotrial

Rueil-Malmaison, France

Sponsors and Collaborators

Shire

Investigators

• Study Director: Study Director; Takeda

More Information

• Responsible Party: Shire
• ClinicalTrials.gov Identifier: NCT01552928
• Other Study ID Numbers: SPD422-111; 2011-005288-26 ( EudraCT Number )
• First Posted: March 13, 2012
• Results First Posted: January 10, 2014
• Last Update Posted: June 9, 2021
• Last Verified: May 2021

Additional relevant MeSH terms:

Moxifloxacin; Anagrelide; Anti-Bacterial Agents; Anti-Infective Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors