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Agrylin (Anagrelide Hydrochloride) - Summary

 
 



AGRYLIN SUMMARY

AGRYLIN®
(anagrelide hydrochloride)
Capsules

Rx only

AGRYLIN® (anagrelide hydrochloride) reduces blood platelet count.

AGRYLIN® Capsules are indicated for the treatment of patients with thrombocythemia, secondary to myeloproliferative disorders, to reduce the elevated platelet count and the risk of thrombosis and to ameliorate associated symptoms including thrombo-hemorrhagic events (see CLINICAL STUDIES, DOSAGE and ADMINISTRATION).


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NEWS HIGHLIGHTS

Published Studies Related to Agrylin (Anagrelide)

Pharmacokinetics, bioequivalence, tolerability, and effects on platelet counts of two formulations of anagrelide in healthy volunteers and patients with thrombocythemia associated with chronic myeloproliferation. [2009.02]
BACKGROUND: Anagrelide hydrochloride is an anti-thrombotic agent indicated for the treatment of essential thrombocythemia (ET). In various previously published clinical trials of 2 branded formulations of anagrelide in patients with ET at high risk for thrombohemorrhagic events, the rates of adverse events and discontinuation were strikingly divergent between brands. Because the formulations and manufacturers differed, the differences in tolerability, as well as platelet counts, might have been related to differences in pharmacokinetic properties between the 2 formulations. OBJECTIVES: The present series of investigations (1) determined the pharmacokinetic profile of anagrelide and its metabolites; (2) compared the pharmacokinetic profiles of the test and reference formulations of anagrelide; (3) investigated the in vitro release of anagrelide as a marker of intragastric anagrelide release of the test and reference formulations; and (4) compared the platelet-reducing effects of the test and reference formulations in patients with thrombocythemia in 2 longitudinal studies over 4 weeks... CONCLUSIONS: The pharmacokinetic properties, adverse event rates, and in vitro dissolution profile differed between the test and reference anagrelide formulations in these healthy volunteers. In patients with ET or thrombocythemia associated with CMPD, platelet counts did not differ significantly from baseline at 4 weeks when subjects were switched from the reference to the test anagrelide formulation.

Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. [2005.07.07]
BACKGROUND: We conducted a randomized comparison of hydroxyurea with anagrelide in the treatment of essential thrombocythemia... CONCLUSIONS: Hydroxyurea plus low-dose aspirin is superior to anagrelide plus low-dose aspirin for patients with essential thrombocythemia at high risk for vascular events. Copyright 2005 Massachusetts Medical Society.

Anagrelide for the treatment of thrombocythaemia in daily clinical practice: a post-marketing observational survey on efficacy and safety performed in Germany. [2010]
BACKGROUND: Myeloproliferative diseases - in particular essential thrombocythaemia (ET) - may be associated with increases in platelet count which put patients at risk of life-threatening complications such as thromboses and severe bleedings... CONCLUSION: Anagrelide was effective in lowering the platelet count and was also well tolerated when used in daily clinical practice. (c) 2010 S. Karger AG, Basel.

Management of refractory essential thrombocythemia with anagrelide in a patient undergoing hemodialysis. [2009.11]
BACKGROUND: Management of essential thrombocythemia (ET) in high-risk patients is difficult because high platelet numbers can lead to vascular occlusive events and bleeding. Therapeutic interventions in ET are limited to hydroxyurea and anagrelide; however, in Europe, anagrelide is contraindicated in patients with chronic renal disease...

Atypical Takotsubo syndrome during anagrelide therapy. [2009.07]
Anagrelide is a phosphodiesterase III inhibitor utilized in the treatment of essential thrombocythemia... To our knowledge, this is one of the first reports of an association between anagrelide therapy and Takotsubo cardiomyopathy.

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Clinical Trials Related to Agrylin (Anagrelide)

Fed Study of Anagrelide Hydrochloride Capsules 1 mg to Agrylin« Capsules 1 mg [Completed]
The objective of this study was to investigate the bioequivalence of Mylan's anagrelide HCl 1 mg capsules to Shire US's Agrylin« 1 mg capsules following a single, oral 1 mg (1 x 1 mg) dose administration under fed conditions.

Fasting Study of Anagrelide Hydrochloride Capsules 1 mg to Agrylin« Capsules 1 mg [Completed]
The objective of this study was to investigate the bioequivalence of Mylan's anagrelide HCl 1 mg capsules to Shire US's Agrylin« 1 mg capsules following a single, oral 1 mg (1 x 1 mg) dose administration under fasting conditions.

Anagrelide Retard vs. Placebo: Efficacy and Safety in "At-risk" Patients With Essential Thrombocythaemia [Recruiting]
This is a multicenter, phase III, randomized, subject and sponsor-blinded, placebo-controlled study to determine the treatment effect of "Anagrelide retard" in subjects with Essential Thrombocythaemia (ET) at "defined risk" (definition of risk criteria: see Inclusion Criteria Section 5. 1) The study is planned as a 2-stage procedure according to Bauer and K÷hne: After recruitment of 140 subjects an interim analysis with re-assessment of sample size is planned in an adaptive manner.

As the confirmatory analysis will be based on a time-to-event evaluation (i. e. time to 1st clinically significant ET related event), there is no stipulated observation time identically applying for all subjects. Yet, with an interim analysis being performed after

having recruited 140 subjects - which is expected to be reached after 1 year - the estimated

observation time for a subject in stage I will also be about 1 year. (Details are explained in the section "Statistical Considerations").

Subjects will be randomized in a 1: 1 ratio to one of the following two arms:

Group A: Anagrelide retard Group B: Placebo

An a priori stratification is planned for the JAK-2 mutational status. For exploratory purposes a post hoc stratification is used for obtaining covariate adjusted results, for the following other potentially predictive factors: sex, age, Factor V Leiden, and BMI.

Dosing will be started with 1 tablet per day for week 1 and will be titrated up according to response (platelet reduction) to 2 tablets in week 2. Dosing may be further increased or decreased according to platelet response in week 3 and 4. However, the maximum dose is 4 tablets (=8mg) per day. After week 4, the maximum dose to achieve optimal platelet counts (<450 G/L) should be maintained (for visit schedule see study flow chart section IV).

To verify a treatment response, platelet counts must be evaluated at every visit. The platelet count values will be withheld from the subjects for the duration of stage I or stage II respectively. The subjects have to agree explicitly to this procedure by signing the Informed Consent form.

This is a patient and sponsor-blinded clinical study. The trial medical is packaged in the blinded fashion to keep the patient unaware (blinded) towards the actual treatment group they were randomized to. The sponsor functions (including medical monitor, pharmacovigilance manager, clinical project manager, trial data manager and trial statistician) with stay blinded in the course of the study until the database lock. Randomization scheme will be prepared by an independent statistician (not otherwise involved in the study), and will be stored securely with no access to it by the sponsor functions mentioned above. The process of randomization (provision of the individual drug-allocation information to the subjects) will be carried out by a trained staff by Harrison, in adherence to the procedures to keep the other blinded functions unaware of this information (blinded). Unblinding envelopes, which contain the treatment code per patient number for identification of treatment in case when a safety-relevant unblinding needed, will be stored at the sponsor's site. At the end of the study, verification of the extent of maintaining the blind by checking if the envelopes have been broken, will take place and will be properly documented. If the sealed envelope will broken to provide treatment identification, the date of breaking the code, the initials of the person who broke the code and the reason will be stated on the envelope.

The operational details on the blinding procedures are outlined in the relevant working guidelines (ARETA Study Working Guideline for idv staff, version 3, dated 22. 07. 2010, and ARETA Study Working Guideline for Harrison, version 1. 0, dated 26. 07. 2010).

Investigator will not be blinded in this study, i. e. in case of a medical need individual patient management will be driven by the full knowledge of the trial related interventions. For the case, the sponsor will need to unblind a patient (e. g. due to safety reasons), the above mentioned (in this section) envelopes will be used.

Only treatment naïve subjects, in respect to cytoreductive drugs with confirmed diagnosis of ET (centralized re-evaluation according to WHO, 2008; see Section 6. 2.1) and assessment of JAK-2 status (centralized re-evaluation of JAK-2 status; see Section 6. 2.2) will be enrolled.

As described above, stage I of the study will be considered as closed as soon as 140 subjects have been recruited. The duration of stage II depends on the result of the re-assessment of sample size.

Once stage 1 is finished, stage 1 subjects will enter into an extension period for a maximum of three years.

A Phase II Study of the Pharmacokinetics of Anagrelide in Elderly and Young ET Patients [Recruiting]
Age related differences in response to a drug could arise from variation in 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

A Study of Anagrelide and Hydroxyurea in High-Risk Essential Thrombocythemia Patients [Recruiting]
Essential thrombocythaemia is a disorder of bone marrow, which causes too many platelets to be produced. Platelets are small cells carried around in the blood, which help form blood clots. When patients have too many platelets, there is a risk of blood clots forming unnecessarily and excessive bleeding. The aim of this study is to gain additional information on the safety profile of Anagrelide (Xagrid(r)) and Hydroxyurea (also known as hydroxycarbamide).

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Reports of Suspected Agrylin (Anagrelide) Side Effects

Intentional Overdose (2)Drug Diversion (2)Gastrointestinal Haemorrhage (1)Pain (1)Mucous Stools (1)Headache (1)Haematemesis (1)Tunnel Vision (1)Overdose (1)Chest Pain (1)more >>


Page last updated: 2010-10-05

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