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

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

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 Overview

• Status: Completed
• Conditions: Primary Myelofibrosis (PMF); Post-Polycythaemia Vera; Essential Thrombocythaemia Myelofibrosis
• Intervention / Treatment: Drug: AZD1480

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Villejuif Cedex, France
    • Research Site
• United States
  • New York
    • New York, New York, United States
      • Research Site
  • Texas
    • Houston, Texas, United States
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; AZD1480	Drug: AZD1480; Oral capsule 2.5 mg, 10 mg and 40 mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: University of Texas; Gustave Roussy, Cancer Campus, Grand Paris; New York City Hoffman Center
• Investigators: Principal Investigator: Srdan Verstovsek, MD, MDACC; Principal Investigator: Ronald Hoffman, MD, Mt. Sinai; Study Director: Becker Hewes, MD, AstraZeneca

Study record dates

Study Major Dates

• Study Start: May 1, 2009
• Primary Completion (ACTUAL): March 1, 2012
• Study Completion (ACTUAL): August 1, 2014

Study Registration Dates

• First Submitted: May 28, 2009
• First Submitted That Met QC Criteria: May 29, 2009
• First Posted (ESTIMATE): June 1, 2009

Study Record Updates

• Last Update Posted (ACTUAL): April 24, 2017
• Last Update Submitted That Met QC Criteria: March 13, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Phase I; Phase II; Bone marrow; Primary Myelofibrosis (PMF); Post-Polycythaemia Vera/Essential Thrombocythaemia Myelofibrosis (Post-PV/ET MF); Myeloproliferative diseases
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Primary Myelofibrosis; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia
• Other Study ID Numbers: D1060C00001