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

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.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00413634

Enrollment

Registered

2006-12-20

Start date

2006-11-13

Completion date

2008-01-22

Last updated

2021-06-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Essential Thrombocythaemia

Brief 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 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

Interventions

DRUGanagrelide hydrochloride

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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Volume of Distribution (Vz/F) 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	—
Cmax of Active Metabolite	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	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	—
Maximum Plasma Concentration (Cmax) of Agrylin	over 1 day	—

Secondary

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

Countries

Spain, Sweden, United Kingdom

Participant flow

Recruitment details

Patients were between 18-50 years (young) and 65 or older (elderly) with a diagnosis of essential thrombocythemia (ET) and receiving a stable dose of anagrelide \<=5mg/day for at least 4 weeks.

Pre-assignment details

The study comprised four phases: Screening (patients take their normal regimen of anagrelide), a run-in period (patients divided their normal anagrelide daily dose equally into two daily doses), Pharmacokinetics (PK) sampling day (patients take normal morning dose), and follow-up (patients were contacted by phone 30 days after PK visit).

Participants by arm

Arm	Count
Agrylin (Young) Anagrelide hydrochloride in ages 18-50 years	12
Agrylin (Elderly) Anagrelide hydrochloride in ages 65 and older	12
Total	24

Baseline characteristics

Characteristic	Total	Agrylin (Young)	Agrylin (Elderly)
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	12 Participants	0 Participants	12 Participants
Age, Categorical Between 18 and 65 years	12 Participants	12 Participants	0 Participants
Age, Continuous	54.2 years STANDARD_DEVIATION 16.5	39.2 years STANDARD_DEVIATION 8.4	69.2 years STANDARD_DEVIATION 3
Region of Enrollment Germany	15 Participants	5 Participants	10 Participants
Region of Enrollment Serbia	2 Participants	2 Participants	0 Participants
Region of Enrollment Spain	2 Participants	1 Participants	1 Participants
Region of Enrollment Sweden	2 Participants	2 Participants	0 Participants
Region of Enrollment United Kingdom	3 Participants	2 Participants	1 Participants
Sex: Female, Male Female	17 Participants	9 Participants	8 Participants
Sex: Female, Male Male	7 Participants	3 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	3 / 12	0 / 12
serious Total, serious adverse events	0 / 12	0 / 12

Outcome results

Primary

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

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Agrylin	6.4 ng.h/ml	Standard Deviation 2.4
Agrylin (Elderly)	Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Agrylin	10.3 ng.h/ml	Standard Deviation 4

p-value: 0.013ANOVA

Primary

AUC of Active Metabolite

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	AUC of Active Metabolite	27.6 ng.h/ml	Standard Deviation 10.9
Agrylin (Elderly)	AUC of Active Metabolite	17.4 ng.h/ml	Standard Deviation 14.8

p-value: 0.027ANOVA

Primary

CL/F of Active Metabolite

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	CL/F of Active Metabolite	36 L/h	Standard Deviation 16
Agrylin (Elderly)	CL/F of Active Metabolite	57 L/h	Standard Deviation 27

p-value: 0.027ANOVA

Primary

Cmax of Active Metabolite

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

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	Cmax of Active Metabolite	7.26 ng/ml	Standard Deviation 3.74
Agrylin (Elderly)	Cmax of Active Metabolite	4.19 ng/ml	Standard Deviation 3.47

p-value: 0.023ANOVA

Primary

Maximum Plasma Concentration (Cmax) of Agrylin

Time frame: over 1 day

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

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	Maximum Plasma Concentration (Cmax) of Agrylin	2.66 ng/ml	Standard Deviation 0.99
Agrylin (Elderly)	Maximum Plasma Concentration (Cmax) of Agrylin	3.63 ng/ml	Standard Deviation 1.44

p-value: 0.092ANOVA

Primary

T 1/2 of Active Metabolite

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	T 1/2 of Active Metabolite	2.7 hours	Standard Deviation 0.5
Agrylin (Elderly)	T 1/2 of Active Metabolite	3.5 hours	Standard Deviation 1.1

p-value: 0.007ANOVA

Primary

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

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	Terminal Half-life (T 1/2) of Agrylin	1.3 hours	Standard Deviation 0.4
Agrylin (Elderly)	Terminal Half-life (T 1/2) of Agrylin	1.4 hours	Standard Deviation 0.3

p-value: 0.378ANOVA

Primary

Time of Maximum Plasma Concentration (Tmax) of Agrylin

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	Time of Maximum Plasma Concentration (Tmax) of Agrylin	1.11 hours	Standard Deviation 0.39
Agrylin (Elderly)	Time of Maximum Plasma Concentration (Tmax) of Agrylin	1.14 hours	Standard Deviation 0.91

p-value: 0.857ANOVA

Primary

Tmax of Active Metabolite

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	Tmax of Active Metabolite	0.92 hours	Standard Deviation 0.26
Agrylin (Elderly)	Tmax of Active Metabolite	1.04 hours	Standard Deviation 0.99

p-value: 0.557ANOVA

Primary

Total Clearance (CL/F) of Agrylin

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	Total Clearance (CL/F) of Agrylin	156 L/h	Standard Deviation 73
Agrylin (Elderly)	Total Clearance (CL/F) of Agrylin	97 L/h	Standard Deviation 70

p-value: 0.013ANOVA

Primary

Volume of Distribution (Vz/F) of Agrylin

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	Volume of Distribution (Vz/F) of Agrylin	286 L	Standard Deviation 125
Agrylin (Elderly)	Volume of Distribution (Vz/F) of Agrylin	195 L	Standard Deviation 137

p-value: 0.035ANOVA

Primary

Vz/F of Active Metabolite

Time frame: over 1 day

Population: PK population

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Agrylin (Young)	Vz/F of Active Metabolite	139 L	Standard Deviation 86
Agrylin (Elderly)	Vz/F of Active Metabolite	277 L	Standard Deviation 203

p-value: 0.011ANOVA

Secondary

Diastolic Blood Pressure

Diastolic blood pressures in patients with ET receiving Agrylin

Time frame: over 1 day

Population: Safety population

Arm	Measure	Group	Value (MEAN)	Dispersion
Agrylin (Young)	Diastolic Blood Pressure	2 hours post-dose	71.3 mmHg	Standard Deviation 7.9
Agrylin (Young)	Diastolic Blood Pressure	1 hour post-dose	72.4 mmHg	Standard Deviation 6.6
Agrylin (Young)	Diastolic Blood Pressure	4 hours post-dose	76.2 mmHg	Standard Deviation 6
Agrylin (Young)	Diastolic Blood Pressure	6 hours post-dose	73.4 mmHg	Standard Deviation 10
Agrylin (Young)	Diastolic Blood Pressure	0.5 hours post-dose	74.8 mmHg	Standard Deviation 7.3
Agrylin (Young)	Diastolic Blood Pressure	8 hours post-dose	76.3 mmHg	Standard Deviation 6.2
Agrylin (Young)	Diastolic Blood Pressure	1.5 hours post-dose	72.8 mmHg	Standard Deviation 6.7
Agrylin (Young)	Diastolic Blood Pressure	12 hours post-dose	76.3 mmHg	Standard Deviation 9.1
Agrylin (Young)	Diastolic Blood Pressure	Baseline	76.9 mmHg	Standard Deviation 7.5
Agrylin (Elderly)	Diastolic Blood Pressure	12 hours post-dose	84.2 mmHg	Standard Deviation 12.4
Agrylin (Elderly)	Diastolic Blood Pressure	Baseline	81.4 mmHg	Standard Deviation 10.3
Agrylin (Elderly)	Diastolic Blood Pressure	0.5 hours post-dose	75.2 mmHg	Standard Deviation 9.9
Agrylin (Elderly)	Diastolic Blood Pressure	1 hour post-dose	72.6 mmHg	Standard Deviation 7.5
Agrylin (Elderly)	Diastolic Blood Pressure	1.5 hours post-dose	71.6 mmHg	Standard Deviation 9.5
Agrylin (Elderly)	Diastolic Blood Pressure	2 hours post-dose	72.8 mmHg	Standard Deviation 7.1
Agrylin (Elderly)	Diastolic Blood Pressure	6 hours post-dose	71.3 mmHg	Standard Deviation 7.6
Agrylin (Elderly)	Diastolic Blood Pressure	8 hours post-dose	75.0 mmHg	Standard Deviation 11.3
Agrylin (Elderly)	Diastolic Blood Pressure	4 hours post-dose	73.0 mmHg	Standard Deviation 9.5

Secondary

Heart Rate

Heart rates in patients with ET receiving Agrylin

Time frame: over 1 day

Population: Safety population

Arm	Measure	Group	Value (MEAN)	Dispersion
Agrylin (Young)	Heart Rate	0.5 hours post-dose	72.4 beats/min	Standard Deviation 8.9
Agrylin (Young)	Heart Rate	4 hours post-dose	75.0 beats/min	Standard Deviation 5.5
Agrylin (Young)	Heart Rate	1.5 hours post-dose	78.1 beats/min	Standard Deviation 7.7
Agrylin (Young)	Heart Rate	6 hours post-dose	75.9 beats/min	Standard Deviation 8.6
Agrylin (Young)	Heart Rate	1 hour post-dose	75.8 beats/min	Standard Deviation 5.5
Agrylin (Young)	Heart Rate	8 hours post-dose	75.5 beats/min	Standard Deviation 6.7
Agrylin (Young)	Heart Rate	2 hours post-dose	74.3 beats/min	Standard Deviation 7
Agrylin (Young)	Heart Rate	12 hours post-dose	73.2 beats/min	Standard Deviation 6
Agrylin (Young)	Heart Rate	Baseline	74.0 beats/min	Standard Deviation 9.6
Agrylin (Elderly)	Heart Rate	12 hours post-dose	71.9 beats/min	Standard Deviation 8.1
Agrylin (Elderly)	Heart Rate	Baseline	70.3 beats/min	Standard Deviation 8.4
Agrylin (Elderly)	Heart Rate	0.5 hours post-dose	77.7 beats/min	Standard Deviation 13.5
Agrylin (Elderly)	Heart Rate	1 hour post-dose	80.6 beats/min	Standard Deviation 11.7
Agrylin (Elderly)	Heart Rate	1.5 hours post-dose	82.7 beats/min	Standard Deviation 12.9
Agrylin (Elderly)	Heart Rate	2 hours post-dose	81.2 beats/min	Standard Deviation 13.8
Agrylin (Elderly)	Heart Rate	4 hours post-dose	74.7 beats/min	Standard Deviation 13.7
Agrylin (Elderly)	Heart Rate	6 hours post-dose	76.9 beats/min	Standard Deviation 11.4
Agrylin (Elderly)	Heart Rate	8 hours post-dose	76.3 beats/min	Standard Deviation 10.1

Secondary

Platelet Count

Platelet counts in patients with ET receiving Agrylin

Time frame: over 1 day

Population: Safety population (defined as all patients who received study treatment)

Arm	Measure	Group	Value (MEAN)	Dispersion
Agrylin (Young)	Platelet Count	Baseline	488.8 x 1,000,000,000/L	Standard Deviation 167.4
Agrylin (Young)	Platelet Count	2 hours post-dose	487.9 x 1,000,000,000/L	Standard Deviation 168.1
Agrylin (Young)	Platelet Count	12 hours post-dose	473.2 x 1,000,000,000/L	Standard Deviation 146
Agrylin (Elderly)	Platelet Count	Baseline	548.5 x 1,000,000,000/L	Standard Deviation 278.7
Agrylin (Elderly)	Platelet Count	2 hours post-dose	539.2 x 1,000,000,000/L	Standard Deviation 258.6
Agrylin (Elderly)	Platelet Count	12 hours post-dose	540.3 x 1,000,000,000/L	Standard Deviation 263.6

Secondary

Systolic Blood Pressure

Systolic blood pressures in patients with ET receiving Agrylin

Time frame: over 1 day

Population: Safety population

Arm	Measure	Group	Value (MEAN)	Dispersion
Agrylin (Young)	Systolic Blood Pressure	0.5 hours post-dose	122.7 mmHg	Standard Deviation 12.9
Agrylin (Young)	Systolic Blood Pressure	4 hours post-dose	122.2 mmHg	Standard Deviation 13.6
Agrylin (Young)	Systolic Blood Pressure	1.5 hours post-dose	122.3 mmHg	Standard Deviation 11.6
Agrylin (Young)	Systolic Blood Pressure	6 hours post-dose	120.2 mmHg	Standard Deviation 16.1
Agrylin (Young)	Systolic Blood Pressure	1.0 hours post-dose	121.8 mmHg	Standard Deviation 11.7
Agrylin (Young)	Systolic Blood Pressure	8 hours post-dose	123.6 mmHg	Standard Deviation 14.5
Agrylin (Young)	Systolic Blood Pressure	2 hours post-dose	121.3 mmHg	Standard Deviation 12.3
Agrylin (Young)	Systolic Blood Pressure	12 hours post-dose	124.7 mmHg	Standard Deviation 13.6
Agrylin (Young)	Systolic Blood Pressure	Baseline	122.2 mmHg	Standard Deviation 9.6
Agrylin (Elderly)	Systolic Blood Pressure	12 hours post-dose	159.8 mmHg	Standard Deviation 28.6
Agrylin (Elderly)	Systolic Blood Pressure	Baseline	154.3 mmHg	Standard Deviation 19.6
Agrylin (Elderly)	Systolic Blood Pressure	0.5 hours post-dose	145.2 mmHg	Standard Deviation 20.3
Agrylin (Elderly)	Systolic Blood Pressure	1.0 hours post-dose	143.7 mmHg	Standard Deviation 21.8
Agrylin (Elderly)	Systolic Blood Pressure	1.5 hours post-dose	140.1 mmHg	Standard Deviation 17.7
Agrylin (Elderly)	Systolic Blood Pressure	2 hours post-dose	139.9 mmHg	Standard Deviation 19.8
Agrylin (Elderly)	Systolic Blood Pressure	4 hours post-dose	133.7 mmHg	Standard Deviation 18.1
Agrylin (Elderly)	Systolic Blood Pressure	6 hours post-dose	141.8 mmHg	Standard Deviation 19.5
Agrylin (Elderly)	Systolic Blood Pressure	8 hours post-dose	136.3 mmHg	Standard Deviation 24.3

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Baseline characteristics

Adverse events

Outcome results

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

AUC of Active Metabolite

CL/F of Active Metabolite

Cmax of Active Metabolite

Maximum Plasma Concentration (Cmax) of Agrylin

T 1/2 of Active Metabolite

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

Time of Maximum Plasma Concentration (Tmax) of Agrylin

Tmax of Active Metabolite

Total Clearance (CL/F) of Agrylin

Volume of Distribution (Vz/F) of Agrylin

Vz/F of Active Metabolite

Diastolic Blood Pressure

Heart Rate

Platelet Count

Systolic Blood Pressure