AOP 03-007 - ANAHYDRET Study
 A single blind, multi-centre, randomised multinational Phase III Study to compare the Efficacy and Tolerability of Anagrelide vs Hydroxyurea in Patients with Essential Thrombocythaemia
   
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Overview
Contact 		AOP 03-007 – ANAHYDRET STUDY
A single blind, multi-centre, randomised multinational Phase III Study to compare the Efficacy and Tolerability of Anagrelide vs Hydroxyurea in Patients with Essential Thrombocythaemia

Study design:
Single blind (only patient blinded), randomised, multicentric phase III study in 20 Centers in CEE.

Sponsor:
AOP Orphan Pharmaceuticals AG,
Wilheminenstr.91/II f/B4,A-1160 Vienna - AUSTRIA
Tel: +43 / 1- 503 72 44; Fax: +43 / 1- 503 72 44-5

Inclusion criteria:
  • > 18 years
  • essential thrombocythemia (according to diagnostic criteria, Appendix I)
  • previously untreated with cytoreductive drugs (e.g. Hydroxy-urea, Interferon alpha, Busulfan etc) or Anagrelide.
  • written informed consent
  • high risk of thrombotic or haemorrhagic complications (according to Appendix I)

Exclusion criteria:
  • previous treatment with cytoreductive drugs or Anagrelide
  • pregnant women or women in childbearing age with inadequate contraception
  • anaphylactoid reactions to active or inactive ingredients
  • known lactose intolerance.
  • cardiovascular diseases grade III-IV (Appendix IV -“Toxicity Criteria…”)
  • severe renal disease (Creatinin Clearance < 30 ml/min)
  • severe liver disease (AST or ALT > 5-times normal)
  • coexisting, malignant, systemic diseases
Randomisation/Patient number allocation:
will be done centrally by sponsor. Before inclusion of a patient the completed assessment form for screening (page 3-8 in CRF) has to be faxed to AOP Orphan Pharmaceuticals for approval. (FAX No: 0043 / 1 / 503 72 44 – 5)


Study Activities (see also Activity Sheet)
1. month: weekly (+/- 3 days) examinations incl. CBC, Compliance (questioning, diary, CTM box, MCV-increase)
month 2 to 6: monthly (+/-1week) examination, incl. CBC, Compliance
month 6 to 12: bimonthly examination, incl. CBC, Compliance

For women in childbearing age a pregnancy test has to be carried out every month.

Additionally before inclusion into the study and upon termination complete blood chemistry and coagulation parameters have to be determined

Administration of Study Drug:
Anagrelide:
1. week: 2 x 1 capsule 0,5 mg (1mg/day)
2. week: 3 or 4 capsules 0,5 mg (1,5 to 2 mg/day)
3. week onwards: dose modification of max, 0,5 mg/day/week.
Reduction of 25-75% if clinically significant adverse drug reactions occur (for definition see protocol 6.1.5).
Temporary therapy-interruption if Hemoglobin < 10 g/dl or thrombocytopenia (plt.ct. < 100x109/l) or other clinically significant adverse drug reactions occur, that did not resolve upon dosereduction.
Maximal daily dose: 5 mg (10 capsules 0,5 mg)
Hydroxyurea:
initial: 3 x 500mg daily. (1500 mg/day)
2. week onwards: dose reduction if WBC decreases (500 mg if 25% decrease, 1000 mg if 50% decrease) or other clin. signif. adverse drug reactions.
Temporary therapy-interruption if WBC decreases by 75% or if WBC < 3x109/l; neutrophile ct.< 1,5x109 /l; Hämoglobin < 10g/dl; or other clinically significant adverse drug reactions occur, that did not resolve upon dose reduction.
4. week onwards: doseescalation of 500 mg/day/week, if plt.ct. > 450x109 /l, WBC > 3x109 /l and Hb > 10g/dl after 4 weeks treatment with 1500 mg.
Maximal daily dose: 2000 mg

Duration of study:
recruitment: 2 years
studyperiod per patient: 1 year
follow up: 5 years


See also:
Appendix I
Activity Sheet