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

This study has been completed.
Sponsor:
Information provided by:
Shire
ClinicalTrials.gov Identifier:
NCT00413634
First received: December 19, 2006
Last updated: June 6, 2014
Last verified: July 2010
  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 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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:


Further study details as provided by Shire:

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 ]
    An active metabolite has therapeutic activity similar to the parent compound and must be considered in therapeutic pharmacokinetics.

  • 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 ]
    Platelet counts in patients with ET receiving Agrylin

  • Heart Rate [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
    Heart rates in patients with ET receiving Agrylin

  • Systolic Blood Pressure [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
    Systolic blood pressures in patients with ET receiving Agrylin

  • Diastolic Blood Pressure [ Time Frame: over 1 day ] [ Designated as safety issue: Yes ]
    Diastolic blood pressures in patients with ET receiving Agrylin


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
Experimental: 1 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
Spain
Hospitl Del Mar
Barcelona, Spain
Sweden
Quintiles Hermelinen
Sandviksgatan, Lulea, Sweden
Quintiles AB Phase I Unit
Strandbodgatan, Uppsala, Sweden
Uppsala Akademiska Sjukhus
Uppsala, Sweden, 75185
United Kingdom
Belfast City Hospital
Belfast, United Kingdom
Sponsors and Collaborators
Shire
Investigators
Principal Investigator: Carlos Besses Raebel Spain
  More Information

Additional Information:
No publications provided by Shire

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Timothy Whitaker, M.D., Shire
ClinicalTrials.gov Identifier: NCT00413634     History of Changes
Other Study ID Numbers: SPD422-203, 2004-004058-20
Study First Received: December 19, 2006
Results First Received: March 5, 2009
Last Updated: June 6, 2014
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

Additional relevant MeSH terms:
Thrombocythemia, Essential
Thrombocytosis
Blood Coagulation Disorders
Blood Platelet Disorders
Bone Marrow Diseases
Hematologic Diseases
Hemorrhagic Disorders
Myeloproliferative Disorders
Anagrelide
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014