Clinical trial NCT00910728: Study to Assess the Safety of AZD1480 in Patients With Myeloproliferative Diseases
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Primary Myelofibrosis (PMF)
Post-Polycythaemia Vera
Essential Thrombocythaemia Myelofibrosis
Keywords: Primary Myelofibrosis (PMF)
Post-Polycythaemia Vera/Essential Thrombocythaemia Myelofibrosis (Post-PV/ET MF)
Myeloproliferative diseases
Phase I
Phase II
Bone marrow
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: University of Texas
name: New York City Hoffman Center
name: Gustave Roussy, Cancer Campus, Grand Paris
First posted: 2009-06-01
Enrollment: 65
Sex: ALL
Minimum age (years): 25
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic Parameters Following Single Dosing: AUC0-12
timeFrame: 0 to 12 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8 and 12 hours post dose)
measure: Pharmacokinetic Parameters Following Single Dosing: AUC0-24
timeFrame: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
measure: Pharmacokinetic Parameters Following Single Dosing:AUC0-inf
timeFrame: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
measure: Pharmacokinetic Parameters Following Multiple Dosing: Cmax,ss
timeFrame: 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
measure: Pharmacokinetic Parameters Following Multiple Dosing: Cmin,ss
timeFrame: 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.
measure: Pharmacokinetic Parameters Following Single Dosing: Cmax
timeFrame: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
measure: Pharmacokinetic Parameters Following Single Dosing: Vz/F
timeFrame: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
measure: Pharmacokinetic Parameters Following Single Dosing: CL/F
timeFrame: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
measure: Pharmacokinetic Parameters Following Multiple Dosing: CLss/F
timeFrame: 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
measure: Pharamcokinetic Parameters Following Single Dosing: Tmax
timeFrame: 0 to 24 hour sampling (Day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose)
measure: Pharamcokinetic Parameters Following Multiple Dosing: Tmax,ss
timeFrame: 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
measure: Inhibition of PSTAT3 (Count)
timeFrame: 2hrs and 4 hrs post dose
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Research Site
state: New York
city: Houston
country: United States
facility: Research Site
state: Texas
city: Villejuif Cedex
country: France
facility: Research Site
Study officials:
affiliation: MDACC
name: Srdan Verstovsek, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mt. Sinai
name: Ronald Hoffman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Gustave Roussy, Cancer Campus, Grand Paris
name: Vincent Ribrag, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca
name: Becker Hewes, MD
role: STUDY_DIRECTOR
References: