The Pharmacokinetics of Anagrelide in Elderly and Young Patients With Essential Thrombocythaemia (ET)

Study Overview
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Brief Summary
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Age related differences in response to a drug could arise from variation in pharmacokinetic (PK) and/or pharmacodynamic (PD) profiles between age groups. Whilst the efficacy and safety profile of anagrelide is well established through a well-documented clinical trial programme in patients of all ages, no formal studies have been carried out to investigate whether the PK profile of anagrelide and its metabolites is altered with age. This study is designed to allow comparisons to be made in terms of pharmacokinetics of anagrelide and its metabolites between elderly (≥ 65 years) and young (18-50 years) ET patients

Official Title
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A Phase II, Open-label, Multicentre, Pharmacokinetic, Pharmacodynamic and Safety Study of Anagrelide Hydrochloride in Young (18-50 Years) and Elderly (≥ 65 Years) Patients With Essential Thrombocythaemia.

Conditions
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Essential Thrombocythaemia

Intervention / Treatment
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* Drug: anagrelide hydrochloride
* Drug: anagrelide hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Young patients aged 18-50 years inclusive or Elderly patients aged 65 years and over Patients must have a confirmed diagnosis of ET. Currently receiving anagrelide hydrochloride at a stable maintenance dose < 5 mg/day for at least 4 weeks. Exclusion Criteria: Diagnosis of any other myeloproliferative disorder. Current use of tobacco in any form (e.g. smoking or chewing) Treatment with any known enzyme altering agents (barbiturates, phenothiazines, cimetidine etc.) within 30 days prior to or during the study. Patients for whom use of another cytoreductive agent in addition to anagrelide is considered necessary for control of platelet count.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Younger Participants (18-50 years)<br> | Drug: anagrelide hydrochloride<br>* Anagrelide hydrochloride 0.5 mg per capsule; participants will be stable on an anagrelide treatment regimen and will take capsules from their own prescription except on the PK day when the participant specific anagrelide dose will be administered from a controlled study specific supply.<br>|
| Experimental: Elderly Participants (≥65 years)<br> | Drug: anagrelide hydrochloride<br>* Anagrelide hydrochloride 0.5 mg per capsule; participants will be stable on an anagrelide regimen and will take capsules from their own prescription except on the PK day when the participant specific anagrelide dose will be administered from a controlled study specific supply.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of Agrylin |  | over 1 day | 
| Time of Maximum Plasma Concentration (Tmax) of Agrylin |  | over 1 day | 
| Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Agrylin |  | over 1 day | 
| Terminal Half-life (T 1/2) of Agrylin |  | over 1 day | 
| Total Clearance (CL/F) of Agrylin |  | over 1 day | 
| Volume of Distribution (Vz/F) of Agrylin |  | over 1 day | 
| Cmax of Active Metabolite | An active metabolite has therapeutic activity similar to the parent compound and must be considered in therapeutic pharmacokinetics. | over 1 day | 
| Tmax of Active Metabolite |  | over 1 day | 
| AUC of Active Metabolite |  | over 1 day | 
| T 1/2 of Active Metabolite |  | over 1 day | 
| CL/F of Active Metabolite |  | over 1 day | 
| Vz/F of Active Metabolite |  | over 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Count | Platelet counts in patients with ET receiving Agrylin | over 1 day | 
| Heart Rate | Heart rates in patients with ET receiving Agrylin | over 1 day | 
| Systolic Blood Pressure | Systolic blood pressures in patients with ET receiving Agrylin | over 1 day | 
| Diastolic Blood Pressure | Diastolic blood pressures in patients with ET receiving Agrylin | over 1 day |