Study to Assess the Safety of AZD1480 in Patients With Myeloproliferative Diseases

Study Overview
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Brief Summary
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This study is being conducted to test study drug AZD1480 to see how it may work to treat myeloproliferative diseases. The main purpose of this study is to determine the safety and tolerability of AZD1480. This is the first time the drug has been given to humans and is classed as a first time in man study. Its main purpose is to establish a safe dosage of the drug and provide additional information on any potential side effects this drug may cause. The study will also assess the blood levels and action of AZD1480 in the body over a period of time and will indicate whether the drug has a therapeutic effect on myeloproliferative diseases.

Official Title
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A PhaseI/II, Open Label Multi-Centre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of the JAK2 Inhibitor AZD1480 Administered Orally to Patients With Primary Myelofibrosis (PMF) and Post-Polycythaemia Vera/Essential Thrombocythaemia Myelofibrosis (Post-PV/ET MF

Conditions
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Primary Myelofibrosis (PMF), Post-Polycythaemia Vera, Essential Thrombocythaemia Myelofibrosis

Intervention / Treatment
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* Drug: AZD1480


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with myelofibrosis requiring therapy Evidence of post-menopausal status or sterile ECOG Performance Status </=2 Exclusion Criteria: Prior therapy with any JAK2 medications Significant lung disorder or lung disease Previous radiation therapy to chest wall or chest infection requiring antibiotic treatment within 28 days before study screening Eye disease of the cornea Patients requiring oxygen supplementation Ejection fraction <45% (ECHO/MUGA) or significant pulmonary hypertension >40 mm Hg (by Echo/Doppler) Forced Expiratory Volume (FEV1)/Forced Vital Capacity (FVC) <70% predicted or >130% predicted Diffusing capacity of the Lung for Carbon Monoxide (DLCO) corrected for hemoglobin <60% predicted, oxygen saturation <88% at rest or after a 6-minute flat walk, without supplemental oxygen Chest infection requiring antibiotics within 7 days of the first dose of Investigational product.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD1480 | Drug: AZD1480<br>* Oral capsule 2.5 mg, 10 mg and 40 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters Following Single Dosing: AUC0-12 | Single dose AUC0-12 (ug*h/L) | 0 to 12 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post dose) | 
| Pharmacokinetic Parameters Following Single Dosing: AUC0-24 | Single dose AUC0-24 (ug*h/L) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) | 
| Pharmacokinetic Parameters Following Single Dosing:AUC0-inf | Single dose AUC(0 to infinity) (ug*h/L) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) | 
| Pharmacokinetic Parameters Following Multiple Dosing: Cmax,ss | Multiple dose Cmax,ss (ug/L) | On Days 1 and 28 at 0, 0,5, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose, and at 0, 2, 4 hours post dose on Days 4 and 10 | 
| Pharmacokinetic Parameters Following Multiple Dosing: Cmin,ss | Multiple dose Cmin,ss (ug/L) | On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post-dose and at 0, 2, 4 hours post-dose on Days 4 and 10. | 
| Pharmacokinetic Parameters Following Single Dosing: Cmax | Single dose Cmax (ug/L) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) | 
| Pharmacokinetic Parameters Following Single Dosing: Vz/F | Single dose Vz/F (L) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) | 
| Pharmacokinetic Parameters Following Single Dosing: CL/F | Single dose CL/F (L/h) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) | 
| Pharmacokinetic Parameters Following Multiple Dosing: CLss/F | Multiple dose CLss/F (L/h) | On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24 hours post dose and at 0, 2, 4 hours post-dose | 
| Pharamcokinetic Parameters Following Single Dosing: Tmax | Single dose Tmax (h) | 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose) | 
| Pharamcokinetic Parameters Following Multiple Dosing: Tmax,ss | Multiple dose Tmax,ss (h) | On Days 1 and 28 at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose and at 0, 2, 4 hours post-dose on Days 4 and 10 | 
| Inhibition of PSTAT3 (Count) | PSTAT3 inhinition | 2hrs and 4 hrs post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Primary Myelofibrosis (PMF), Post-Polycythaemia Vera/Essential Thrombocythaemia Myelofibrosis (Post-PV/ET MF), Myeloproliferative diseases, Phase I, Phase II, Bone marrow