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

NCT00910728 | Completed Phase 1 Results

• 1 other identifier: D1060C00001
• Study Type: interventional
• Target: 65
• Locations: 2 countries
• Sites: 3

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.

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

Outcome Measures

Primary Outcomes (12)

• 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

Study Arms (1)

1

EXPERIMENTAL

AZD1480

Drug: AZD1480

Interventions

AZD1480 DRUG

Oral capsule 2.5 mg, 10 mg and 40 mg

1

Eligibility Criteria

• Age: 25 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with myelofibrosis requiring therapy
• Evidence of post-menopausal status or sterile
• ECOG Performance Status \</=2

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• University of Texas: collaborator
• New York City Hoffman Center: collaborator
• Gustave Roussy, Cancer Campus, Grand Paris: collaborator

Study Sites (3)

Research Site

New York, New York, United States

Location

Research Site

Houston, Texas, United States

Location

Research Site

Villejuif, France

Location

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

AZD 1480

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Dr Gregory Curt, MD
• Organization: AstraZeneca

Gregory.Curt@astrazeneca.com

+1 301 398 0109

Study Officials

• Srdan Verstovsek, MD

  MDACC

  PRINCIPAL INVESTIGATOR

• Ronald Hoffman, MD

  Mt. Sinai

  PRINCIPAL INVESTIGATOR

• Vincent Ribrag, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  PRINCIPAL INVESTIGATOR

• Becker Hewes, MD

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2009
• First Posted: June 1, 2009
• Study Start: May 1, 2009
• Primary Completion: March 1, 2012
• Study Completion: August 1, 2014
• Last Updated: April 24, 2017
• Results First Posted: April 24, 2017

Record last verified: 2017-03

Locations

FR (1); US (2)