Anagrelide Retard in Essential Thrombocythemia

NCT02076815 | Completed Phase 3 DMC

• 2 other identifiers: AOP180072013-003410-41
• Study Type: interventional
• Target: 106
• Locations: 5 countries
• Sites: 19

Brief Summary

The purpose of this study is determine whether Anagrelide Retard is non-inferior to anagrelide immediate release form in treatment of essential thrombocythemia. Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterised by a sustained increase in platelet counts above the normal value (\> 450 x 109/L) and increased megakaryopoiesis in the bone marrow, without secondary causes of thrombocytosis. Anagrelide hydrochloride selectively reduces platelet numbers by inhibiting megakaryocyte development and maturation in humans, without affecting other cell lineages. Anagrelide Retard is a new, prolonged release (PR) tablet formulation of anagrelide developed by AOP Orphan Pharmaceuticals AG. The rationale for developing this new formulation is based on the assumption of having a better tolerability while maintaining an efficacy comparable to that of the immediate release formulation. The effects of Anagrelide Retard and Thromboreductin® will be compared in terms of mean platelet count measured by a central laboratory/centralized method at 3 time points during the maintenance phase.

Conditions

Essential Thrombocythemia

Keywords

myeloproliferative neoplasm; essential thrombocythemia; high risk patients; anagrelide

Outcome Measures

Primary Outcomes (1)

• Platelet count

  Mean value from three measurements

  weeks 13-17

Secondary Outcomes (11)

• platelet response

  weeks 13-17

• Time from randomization to entering maintenance period

  up to 12 weeks

• Study drug administration

  weeks 1-17

• Change in platelet counts in the titration period

  baseline, week 12

• Time from randomization until withdrawal

  up to 17 weeks

Other Outcomes (3)

• Quality of Life

  at week 1 and week 13

• Plasma anagrelide concentration

  At week 13, 15 and 17

• Plasma anagrelide concentration

  1 min prior study treatment intake (morning dose), and 0.5, 1, 2, 3, 4, 6, 8, 10,12 (followed by evening dose), 13, 14, 15, 16, 18, 20, 24 hours after study treatment intake (morning dose)

Study Arms (2)

Anagrelide retard

EXPERIMENTAL

Anagrelide Retard prolonged-release formulation

Drug: Anagrelide retard

Thromboreductin

ACTIVE COMPARATOR

Anagrelide immediate release formulation

Drug: Thromboreductin

Interventions

Anagrelide retard DRUG

Overencapsulated tablets or matched placebo, twice daily, 2-12 weeks titration to achieve stable platelet count, followed by 4 more weeks

Also known as: Anagrelide retard 2 mg film coated tablet, ANAT2

Anagrelide retard

Thromboreductin DRUG

Overencapsulated capsule, twice daily, 2-12 weeks titration to achieve the stable platelet count, followed by 4 more weeks

Also known as: Anagrelide 0.5 mg capsule, ANAC05

Thromboreductin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• willing and able to give written informed consent prior to any study specific procedures and able to comply with the trial protocol
• confirmed diagnosis of ET according to 2008 WHO diagnostic criteria\* (Swerdlow et al, 2008), defined as meeting all four criteria
• at high risk of experiencing ET-related events, indicated for Thromboreductin® treatment as defined by one or more of the following criteria: age ≥ 60 years, platelet counts ≥ 1000 G/L, increase of platelet count ≥ 300 G/L within 3 months, severe thrombohemorrhagic or ischemic symptoms in anamnesis
• either currently treated with anagrelide
• or ET treatment naive
• or anagrelide naive

You may not qualify if:

• Diagnosis of any myeloproliferative disorder other than ET
• Any known cause for a secondary thrombocytosis
• ET currently well controlled by another cytoreductive treatment than Anagrelide and the opportunity to continue to receive this treatment
• ET currently treated with combination of any two of the following agents: anagrelide, hydroxyurea, interferons, busulfan
• Hypersensitivity to either active or non-active ingredients of anagrelide or to any other excipients of the investigational products
• Known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption
• Cardiovascular disease grade 3 with a negative benefit/risk assessment or grade 4 (South West Oncology Group; Green and Weiss, 1992)
• Clinically significant abnormal laboratory values (excluding markers for ET) in investigator's opinion
• Severe renal insufficiency (creatinine clearance \<30 ml/min)
• Moderate to severe hepatic insufficiency (ALT or AST \> 5 times upper normal limit \[UNL\])
• White blood count (WBC) ≥ 15 G/L at screening
• Diagnosis of any malignancy, other than ET (except basal cell and squamous cell carcinomas of the skin and carcinoma in situ of the cervix that have been completely excised and are considered cured), within the last 3 years, or coexisting malignant, systemic disease
• Poorly controlled diabetes mellitus
• Known infection with hepatitis B, hepatitis C or HIV
• Pregnant or lactating women

Sponsors & Collaborators

• AOP Orphan Pharmaceuticals AG: lead

Study Sites (19)

AOP Orphan Investigational Site Austria 2

Linz, A-4040, Austria

Location

AOP Orphan Investigational Site Austria 1

Vienna, A-1090, Austria

Location

AOP Orphan Investigational Site Austria 3

Wels, A-4600, Austria

Location

AOP Orphan Investigational Site Bulgaria 1

Pleven, 5800, Bulgaria

Location

AOP Orphan Investigational Site Bulgaria 2

Sofia, 1407, Bulgaria

Location

AOP Orphan Investigational Site Lithuania 1

Kaunas, LT-50009, Lithuania

Location

AOP Orphan Investigational Site Lithuania 2

Klaipėda, LT-92288, Lithuania

Location

AOP Orphan Investigational Site Poland 5

Bialystok, 15-276, Poland

Location

AOP Orphan Insvestigational Site Poland 6

Gdansk, 80-952, Poland

Location

AOP Orphan Investigational Site Poland 4

Katowice, 40-027, Poland

Location

AOP Orphan Investigational Site Poland 3

Lublin, 20-081, Poland

Location

AOP Orphan Investigational Site Poland 2

Torun, 87-100, Poland

Location

AOP Orphan Investigational Site Poland 1

Warsaw, 02-776, Poland

Location

AOP Orphan Investigational Site Russia 1

Moscow, 125167, Russia

Location

AOP Orphan Investigational Site Russia 2

Saint Petersburg, 191024, Russia

Location

AOP Orphan Investigational Site Russia 5

Saint Petersburg, 194291, Russia

Location

AOP Orphan Investigational Site Russia 4

Saint Petersburg, 196084, Russia

Location

AOP Orphan Investigational Site Russia 6

Volgograd, 400138, Russia

Location

AOP Orphan Investigational Site Russia 3

Yaroslavl, 150062, Russia

Location

MeSH Terms

Conditions

Thrombocythemia, Essential; Myeloproliferative Disorders

Interventions

anagrelide

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Thrombocytosis; Blood Platelet Disorders; Bone Marrow Diseases; Hemorrhagic Disorders

Study Officials

• Heinz Gisslinger, Prof., MD

  Vienna Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2014
• First Posted: March 4, 2014
• Study Start: February 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: April 1, 2015
• Last Updated: July 29, 2015

Record last verified: 2015-07

Locations

LI (2); BU (2); PL (6); RU (6); AU (3)