Clinical trial NCT01552928: Effect of Anagrelide Hydrochloride on Any Changes in Heart Function in Healthy Volunteers
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-03-13
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals From Time-Matched Analysis by Largest Time Point
timeFrame: Over 12 hours post-dose
measure: Mean Difference Changes From Baseline Versus Placebo in Heart Rate From Time-Matched Analysis by Largest Time Point
timeFrame: Over 12 hours post-dose
measure: Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals From Time-Matched Analysis by Largest Time Point
timeFrame: Over 12 hours post-dose
measure: Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals From Time-Matched Analysis by Largest Time Point
timeFrame: Over 12 hours post-dose
measure: Mean Difference Changes From Baseline Versus Placebo in QT Intervals From Time-Matched Analysis by Largest Time Point
timeFrame: Over 12 hours post-dose
Secondary outcomes:
measure: Mean Difference Changes From Baseline Versus Placebo in QTcNi Intervals at Subject-Specific Time of Maximum Plasma Concentration (Tmax)
timeFrame: Over 12 hours post-dose
measure: Mean Difference Changes From Baseline Versus Placebo in Heart Rate at Subject-Specific Tmax
timeFrame: Over 12 hours post-dose
measure: Mean Difference Changes From Baseline Versus Placebo in QTcF Intervals at Subject-Specific Tmax
timeFrame: Over 12 hours post-dose
measure: Mean Difference Changes From Baseline Versus Placebo in QTcB Intervals at Subject-Specific Tmax
timeFrame: Over 12 hours post-dose
measure: Mean Difference Changes From Baseline Versus Placebo in QT Intervals at Subject-Specific Tmax
timeFrame: Over 12 hours post-dose
measure: Maximum Plasma Concentration (Cmax) of 0.5 mg Anagrelide in Males and Females
timeFrame: Over 12 hours post-dose
measure: Maximum Plasma Concentration (Cmax) of 2.5 mg Anagrelide in Males and Females
timeFrame: Over 12 hours post-dose
measure: Maximum Plasma Concentration (Cmax) of Metabolite of 0.5 mg Anagrelide (BCH24426) in Males and Females
timeFrame: Over 12 hours post-dose
measure: Maximum Plasma Concentration (Cmax) of Metabolite of 2.5 mg Anagrelide (BCH24426) in Males and Females
timeFrame: Over 12 hours post-dose
Other outcomes:
Locations:
city: Rueil-Malmaison
country: France
facility: Biotrial
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: