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

Phase 1

Completed

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

Interventions: Drug: AZD1480

Registration Number: NCT00910728

Lead Sponsor: AstraZeneca

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 65

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	AZD1480	AZD1480

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic Parameters Following Single Dosing: AUC0-12	0 to 12 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post dose)	Single dose AUC0-12 (ug\*h/L)
Pharmacokinetic Parameters Following Single Dosing: Vz/F	0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)	Single dose Vz/F (L)
Pharamcokinetic Parameters Following Single Dosing: Tmax	0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)	Single dose Tmax (h)
Pharmacokinetic Parameters Following Multiple Dosing: Cmax,ss	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	Multiple dose Cmax,ss (ug/L)
Pharmacokinetic Parameters Following Single Dosing: Cmax	0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)	Single dose Cmax (ug/L)
Pharmacokinetic Parameters Following Multiple Dosing: Cmin,ss	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.	Multiple dose Cmin,ss (ug/L)
Pharmacokinetic Parameters Following Single Dosing: CL/F	0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)	Single dose CL/F (L/h)
Pharmacokinetic Parameters Following Single Dosing: AUC0-24	0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)	Single dose AUC0-24 (ug\*h/L)
Pharmacokinetic Parameters Following Single Dosing:AUC0-inf	0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)	Single dose AUC(0 to infinity) (ug\*h/L)
Pharmacokinetic Parameters Following Multiple Dosing: CLss/F	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	Multiple dose CLss/F (L/h)
Pharamcokinetic Parameters Following Multiple Dosing: Tmax,ss	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	Multiple dose Tmax,ss (h)
Inhibition of PSTAT3 (Count)	2hrs and 4 hrs post dose	PSTAT3 inhinition