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

Primary Purpose

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

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

AZD1480

About this trial

This is an interventional other trial for Primary Myelofibrosis (PMF) focused on measuring Primary Myelofibrosis (PMF), Post-Polycythaemia Vera/Essential Thrombocythaemia Myelofibrosis (Post-PV/ET MF), Myeloproliferative diseases, Phase I, Phase II, Bone marrow

Eligibility Criteria

25 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Research Site
Research Site
Research Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm Description

AZD1480

Outcomes

Primary Outcome Measures

Pharmacokinetic Parameters Following Single Dosing: AUC0-12

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

Pharmacokinetic Parameters Following Single Dosing: AUC0-24

Single dose AUC0-24 (ug*h/L)

Pharmacokinetic Parameters Following Single Dosing:AUC0-inf

Single dose AUC(0 to infinity) (ug*h/L)

Pharmacokinetic Parameters Following Multiple Dosing: Cmax,ss

Multiple dose Cmax,ss (ug/L)

Pharmacokinetic Parameters Following Multiple Dosing: Cmin,ss

Multiple dose Cmin,ss (ug/L)

Pharmacokinetic Parameters Following Single Dosing: Cmax

Single dose Cmax (ug/L)

Pharmacokinetic Parameters Following Single Dosing: Vz/F

Single dose Vz/F (L)

Pharmacokinetic Parameters Following Single Dosing: CL/F

Single dose CL/F (L/h)

Pharmacokinetic Parameters Following Multiple Dosing: CLss/F

Multiple dose CLss/F (L/h)

Pharamcokinetic Parameters Following Single Dosing: Tmax

Single dose Tmax (h)

Pharamcokinetic Parameters Following Multiple Dosing: Tmax,ss

Multiple dose Tmax,ss (h)

Inhibition of PSTAT3 (Count)

PSTAT3 inhinition

Secondary Outcome Measures

Full Information

NCT ID

NCT00910728

First Posted

May 28, 2009

Last Updated

March 13, 2017

Sponsor

AstraZeneca

Collaborators

University of Texas, New York City Hoffman Center, Gustave Roussy, Cancer Campus, Grand Paris

1. Study Identification

Unique Protocol Identification Number

NCT00910728

Brief Title

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

2. Study Status

Record Verification Date

March 2017

Overall Recruitment Status

Completed

Study Start Date

May 2009 (undefined)

Primary Completion Date

March 2012 (Actual)

Study Completion Date

August 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AstraZeneca

Collaborators

University of Texas, New York City Hoffman Center, Gustave Roussy, Cancer Campus, Grand Paris

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

AZD1480

Intervention Type

Drug

Intervention Name(s)

AZD1480

Intervention Description

Oral capsule 2.5 mg, 10 mg and 40 mg

Primary Outcome Measure Information:

Title

Pharmacokinetic Parameters Following Single Dosing: AUC0-12

Description

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)

Title

Pharmacokinetic Parameters Following Single Dosing: AUC0-24

Description

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)

Title

Pharmacokinetic Parameters Following Single Dosing:AUC0-inf

Description

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)

Title

Pharmacokinetic Parameters Following Multiple Dosing: Cmax,ss

Description

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

Title

Pharmacokinetic Parameters Following Multiple Dosing: Cmin,ss

Description

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.

Title

Pharmacokinetic Parameters Following Single Dosing: Cmax

Description

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)

Title

Pharmacokinetic Parameters Following Single Dosing: Vz/F

Description

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)

Title

Pharmacokinetic Parameters Following Single Dosing: CL/F

Description

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)

Title

Pharmacokinetic Parameters Following Multiple Dosing: CLss/F

Description

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

Title

Pharamcokinetic Parameters Following Single Dosing: Tmax

Description

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)

Title

Pharamcokinetic Parameters Following Multiple Dosing: Tmax,ss

Description

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

Title

Inhibition of PSTAT3 (Count)

Description

PSTAT3 inhinition

Time Frame

2hrs and 4 hrs post dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

99 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Srdan Verstovsek, MD

Organizational Affiliation

MDACC

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Ronald Hoffman, MD

Organizational Affiliation

Mt. Sinai

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Vincent Ribrag, MD

Organizational Affiliation

Gustave Roussy, Cancer Campus, Grand Paris

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Becker Hewes, MD

Organizational Affiliation

AstraZeneca

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

New York

State/Province

New York

Country

United States

Facility Name

Research Site

City

Houston

State/Province

Texas

Country

United States

Facility Name

Research Site

City

Villejuif Cedex

Country

France

12. IPD Sharing Statement

Learn more about this trial

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

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