The Pharmacokinetics of Anagrelide in Elderly and Young Patients With Essential Thrombocythaemia (ET) - Full Text View

Sponsored by:	Shire Pharmaceutical Development
Information provided by:	Shire Pharmaceutical Development
ClinicalTrials.gov Identifier:	NCT00413634

Purpose

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

Condition	Intervention	Phase
Essential Thrombocythaemia	Drug: anagrelide hydrochloride	Phase II

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Parallel Assignment, Pharmacokinetics/Dynamics Study
Official Title:	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.

Resource links provided by NLM:

Genetics Home Reference related topics: hemophilia

Drug Information available for: Anagrelide hydrochloride Anagrelide

U.S. FDA Resources

Further study details as provided by Shire Pharmaceutical Development:

Primary Outcome Measures:

Maximum Plasma Concentration (Cmax) of Agrylin [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Time of Maximum Plasma Concentration (Tmax) of Agrylin [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Agrylin [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Terminal Half-life (T 1/2) of Agrylin [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Total Clearance (CL/F) of Agrylin [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Volume of Distribution (Vz/F) of Agrylin [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Cmax of Active Metabolite [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Tmax of Active Metabolite [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
AUC of Active Metabolite [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
T 1/2 of Active Metabolite [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
CL/F of Active Metabolite [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Vz/F of Active Metabolite [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Platelet Count [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Heart Rate [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Systolic Blood Pressure [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
Diastolic Blood Pressure [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]

Enrollment:	24
Study Start Date:	August 2006
Study Completion Date:	March 2008
Primary Completion Date:	January 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: anagrelide hydrochloride Anagrelide hydrochloride 0.5 mg per capsule; patients will be stable on an anagrelide treatment regimen and will take capsules from their own prescription except on the PK day when the patient specific anagrelide dose will be administered from a controlled study specific supply.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00413634

Locations

Spain
Hospitl Del Mar
Barcelona, Spain
Sweden
Uppsala Akademiska Sjukhus
Uppsala, Sweden, 75185
Sweden, Lulea
Quintiles Hermelinen
Sandviksgatan, Lulea, Sweden
Sweden, Uppsala
Quintiles AB Phase I Unit
Strandbodgatan, Uppsala, Sweden
United Kingdom
Belfast City Hospital
Belfast, United Kingdom

Sponsors and Collaborators

Shire Pharmaceutical Development

Investigators

Principal Investigator:

Carlos Besses Raebel

Spain

More Information

Additional Information:

FDA-approved Label This link exits the ClinicalTrials.gov site

Synopsis of Study Results This link exits the ClinicalTrials.gov site

FDA Recall Information This link exits the ClinicalTrials.gov site

FDA Medical Product Safety Alerts This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Shire ( Timothy Whitaker, M.D. )
Study ID Numbers:	SPD422-203
Study First Received:	December 19, 2006
Results First Received:	March 5, 2009
Last Updated:	August 19, 2009
ClinicalTrials.gov Identifier:	NCT00413634 History of Changes
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency; Germany: Federal Institute for Drugs and Medical Devices; Sweden: Medical Products Agency; Spain: Ministry of Health

Study placed in the following topic categories:

Hematologic Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Myeloproliferative Disorders
Fibrinolytic Agents
Cardiovascular Agents
Hemostatic Disorders
Thrombocytopathy
Fibrin Modulating Agents

Hemorrhagic Disorders
Thrombocytosis
Thrombocythemia, Hemorrhagic
Hemorrhagic Thrombocythemia
Platelet Aggregation Inhibitors
Essential Thrombocytosis
Bone Marrow Diseases
Anagrelide

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Hematologic Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hematologic Agents
Myeloproliferative Disorders
Fibrinolytic Agents
Cardiovascular Agents
Pharmacologic Actions

Fibrin Modulating Agents
Hemorrhagic Disorders
Therapeutic Uses
Thrombocytosis
Thrombocythemia, Hemorrhagic
Platelet Aggregation Inhibitors
Bone Marrow Diseases
Anagrelide

ClinicalTrials.gov processed this record on September 11, 2009