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

AstraZeneca65 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

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

Interventions

Eligibility

Sex: ALLMin age: 25 YearsMax age: 99 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Pharmacokinetic Parameters Following Single Dosing: AUC0-12

Single dose AUC0-12 (ug\*h/L)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 2hrs and 4 hrs post dose

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

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes