Essential ThrombocythaemiaPhase 2NCT00413634

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

A Phase 2 study testing anagrelide hydrochloride in people with Essential Thrombocythaemia, run by Shire at 5 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Essential Thrombocythaemia
What is being tested?: anagrelide hydrochloride
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 24 participants
Where: 5 sitesin 3 countries
Study dates: 13 Nov 2006to 22 Jan 2008
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

5 sites in 3 countries.

Country

City, postcode or hospital

5 sites in 3 countries

Sweden3 sites

Quintiles Hermelinen
Luleå
Uppsala Akademiska Sjukhus
Uppsala, 75185
Quintiles AB Phase I Unit
Uppsala

Other trials in Sweden

Spain1 site

Hospitl Del Mar
Barcelona

Other trials in Spain

United Kingdom1 site

Belfast City Hospital
Belfast

Other trials in United Kingdom

About this 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.

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

Conditions: Essential Thrombocythaemia
Being tested: anagrelide hydrochloride
Medical subject headings: Thrombocythemia, Essential

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

anagrelide hydrochlorideDrug
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.
anagrelide hydrochlorideDrug
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.

Study groups in NCT00413634
Study group	Role	What they receive
Younger Participants (18-50 years)	Experimental	Not described Receives: Drug: anagrelide hydrochloride
Elderly Participants (≥65 years)	Experimental	Not described Receives: Drug: anagrelide hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Plasma Concentration (Cmax) of Agrylin
Measured: over 1 day
Time of Maximum Plasma Concentration (Tmax) of Agrylin
Measured: over 1 day
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Agrylin
Measured: over 1 day
Terminal Half-life (T 1/2) of Agrylin
Measured: over 1 day
Total Clearance (CL/F) of Agrylin
Measured: over 1 day
Volume of Distribution (Vz/F) of Agrylin
Measured: 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.
Measured: over 1 day
Tmax of Active Metabolite
Measured: over 1 day
AUC of Active Metabolite
Measured: over 1 day
T 1/2 of Active Metabolite
Measured: over 1 day
CL/F of Active Metabolite
Measured: over 1 day
Vz/F of Active Metabolite
Measured: over 1 day

Secondary outcomes (4)

Platelet Count
Platelet counts in patients with ET receiving Agrylin
Measured: over 1 day
Heart Rate
Heart rates in patients with ET receiving Agrylin
Measured: over 1 day
Systolic Blood Pressure
Systolic blood pressures in patients with ET receiving Agrylin
Measured: over 1 day
Diastolic Blood Pressure
Diastolic blood pressures in patients with ET receiving Agrylin
Measured: over 1 day

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

13 Nov 200622 Jan 2008

First posted20 Dec 2006 (estimated)
Study start13 Nov 2006
Primary completion22 Jan 2008
Study completion22 Jan 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Essential ThrombocythaemiaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 24 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00413634
Sponsor's protocol ID: SPD422-203
Other IDs: 2004-004058-20, 2004
Status last verified: Jun 2021
First submitted: 19 Dec 2006
Last updated: 29 Jun 2021
Results posted: Yes, on ClinicalTrials.gov

Publications

Besses C, Zeller W, Alvarez-Larran A, Coll R, Troy S, Purkayastha J, Martin P, Freitag C. Pharmacokinetics and tolerability of anagrelide hydrochloride in young (18 - 50 years) and elderly (>/= 65 years) patients with essential thrombocythemia. Int J Clin Pharmacol Ther. 2012 Nov;50(11):787-96. doi: 10.5414/CP201711.
PubMed 22943924

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Essential Thrombocythaemia trials

Study at a glance

From the registry record, last updated by the sponsor on 29 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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.
ClinicalTrials.gov ID: NCT00413634
Acronym / sponsor ID: SPD422-203
Conditions: Essential Thrombocythaemia
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 24 participants (actual)
Lead sponsor: ShireIndustry (pharma, biotech, devices)
Study start: 13 Nov 2006 (actual)
Primary completion: 22 Jan 2008 (actual)
Study completion: 22 Jan 2008 (actual)
First posted: 20 Dec 2006 (estimated)
Results: Posted 2 Jun 2009

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Younger Participants (18-50 years)	Experimental	Drug: anagrelide hydrochloride
Elderly Participants (≥65 years)	Experimental	Drug: anagrelide hydrochloride

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (4 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
anagrelide hydrochlorideAnagrelide 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.	Drug	Younger Participants (18-50 years)
anagrelide hydrochlorideAnagrelide 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.	Drug	Elderly Participants (≥65 years)

Primary outcome

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

4 secondary outcomes

Platelet Count
Time frame: over 1 day
Heart Rate
Time frame: over 1 day
Systolic Blood Pressure
Time frame: over 1 day
Diastolic Blood Pressure
Time frame: over 1 day

Results and safety

Results posted to the registry on 2 Jun 2009, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Agrylin (Young)	12	12
Agrylin (Elderly)	12	12

Primary outcome: Maximum Plasma Concentration (Cmax) of Agrylin

Time frame: over 1 day. Geometric mean (Standard Deviation). Unit: ng/ml

Measure	Agrylin (Young) n = 12	Agrylin (Elderly) n = 12
Value	2.66 (0.99)	3.63 (1.44)

Agrylin (Young) vs Agrylin (Elderly): p = 0.092, ANOVA

Population analysed: PK population (defined as all patients with post-dose drug concentration data)

Primary outcome: Time of Maximum Plasma Concentration (Tmax) of Agrylin

Time frame: over 1 day. Geometric mean (Standard Deviation). Unit: hours

Measure	Agrylin (Young) n = 12	Agrylin (Elderly) n = 12
Value	1.11 (0.39)	1.14 (0.91)

Agrylin (Young) vs Agrylin (Elderly): p = 0.857, ANOVA

Population analysed: PK population

Primary outcome: Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Agrylin

Time frame: over 1 day. Geometric mean (Standard Deviation). Unit: ng.h/ml

Measure	Agrylin (Young) n = 12	Agrylin (Elderly) n = 12
Value	6.4 (2.4)	10.3 (4.0)

Agrylin (Young) vs Agrylin (Elderly): p = 0.013, ANOVA

Population analysed: PK population

Primary outcome: Terminal Half-life (T 1/2) of Agrylin

Time frame: over 1 day. Geometric mean (Standard Deviation). Unit: hours

Measure	Agrylin (Young) n = 12	Agrylin (Elderly) n = 12
Value	1.3 (0.4)	1.4 (0.3)

Agrylin (Young) vs Agrylin (Elderly): p = 0.378, ANOVA

Population analysed: PK population

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Agrylin (Young)	0 of 12 (0%)	3 of 12 (25%)	Not reported
Agrylin (Elderly)	0 of 12 (0%)	0 of 12 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 22943924Besses C, Zeller W, Alvarez-Larran A, Coll R, Troy S, Purkayastha J, Martin P, Freitag C. Pharmacokinetics and tolerability of anagrelide hydrochloride in young (18 - 50 years) and elderly (>/= 65 years) patients with essential thrombocythemia. Int J Clin Pharmacol Ther. 2012 Nov;50(11):787-96. doi: 10.5414/CP201711.
FDA-approved LabelLink provided by the sponsor.
FDA Recall InformationLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Study Director study director

Takeda

5 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing anagrelide hydrochloride in people with Essential Thrombocythaemia, run by Shire at 5 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Sweden, Spain, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Jun 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Plasma Concentration (Cmax) of Agrylin (time frame: over 1 day). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00413634, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2021.