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

NCT01552928 | Completed Phase 1 Results

• 2 other identifiers: SPD422-1112011-005288-26
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (9)

• Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals at Subject-Specific Time of Maximum Plasma Concentration (Tmax)

  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

  Over 12 hours post-dose

• Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals at Subject-Specific Tmax

  Over 12 hours post-dose

• Mean Difference Changes From Baseline Versus Placebo in QT Intervals at Subject-Specific Tmax

  Over 12 hours post-dose

Study Arms (4)

Anagrelide Therapeutic (0.5 mg)

EXPERIMENTAL

Drug: Anagrelide 0.5 mg

Anagrelide Supratherapeutic (2.5 mg)

EXPERIMENTAL

Drug: Anagrelide 2.5 mg

Moxifloxacin

ACTIVE COMPARATOR

Drug: Moxifloxacin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Anagrelide 0.5 mg DRUG

0.5mg Anagrelide single oral dose

Also known as: Agrylin, Xagrid

Anagrelide Therapeutic (0.5 mg)

Anagrelide 2.5 mg DRUG

2.5mg Anagrelide single oral dose

Anagrelide Supratherapeutic (2.5 mg)

Moxifloxacin DRUG

400 mg Moxifloxacin single oral dose

Moxifloxacin

Placebo DRUG

Anagrelide placebo + Moxifloxacin placebo single oral dose

Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Shire: lead

Study Sites (1)

Biotrial

Rueil-Malmaison, France

Location

MeSH Terms

Interventions

anagrelide; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2012
• First Posted: March 13, 2012
• Study Start: March 29, 2012
• Primary Completion: July 25, 2012
• Study Completion: July 25, 2012
• Last Updated: June 9, 2021
• Results First Posted: January 10, 2014

Record last verified: 2021-05

Locations

FR (1)