An Open Label, Single Centre Mass Balance C14 Study in Patients With Acute Myeloid Leukaemia (AML)

A Phase I Open, Non-randomised, Single-centre Study to Assess the Metabolism, Excretion and Pharmacokinetics of AZD1152 and AZD1152 hQPA Following Intravenous Administration of [14C]-AZD1152 in Patients With Acute Myeloid Leukaemia (AML)

The purpose of the study is to assess how AZD1152 is absorbed or excreted in and out of the body in patients with Acute Myeloid Leukaemia (AML).

Study Overview

• Status: Completed
• Conditions: Acute Myeloid Leukaemia
• Intervention / Treatment: Drug: AZD1152; Drug: C14 AZD1152

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with relapsed or refractory AML for which no standard therapies are anticipated to result in durable remission. Or, patients with newly diagnosed AML who are not considered to be suitable for standard induction and consolidation chemotherapy
• Ability to stay in hospital for up to 9 days on the [14C] AZD1152 treatment cycle.
• Subjects who have relapsed > 1 year following myeloablative therapy with allogeneic bone marrow or stem cell transplantation may be eligible if they have no or limited evidence of extensive graft-versus-host disease

Exclusion Criteria:

• QTc interval ≥470 ms calculated from a single ECG reading or a mean of 3 ECG readings using Fridericia's or Bazett's correction
• Administration of hydroxyurea to control peripheral blood counts is prohibited within 24 hours prior to first dose of study drug
• Any chemotherapy or radiotherapy within 14 days prior to starting the study (not including palliative radiotherapy at focal sites)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD1152; 100 mg Lyophile 5 mL Diluent	Drug: AZD1152; 100mg Lyophile, 5mL Diluent IV infusion
Experimental: C14 AZD1152; AZD1152 radiolabelled IV solution. 1.05 mg/ml will be presented as a 15 ml fill in a 20 ml vial.	Drug: C14 AZD1152; radiolabelled IV solution, 1.05 mg/ml presented as 15 ml fill in 20ml vial infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The concentration of total radioactivity, AZD1152 and AZD1152 hQPA in plasma and their ratios, the concentration of total radioactivity in blood and its blood/plasma concentration ratios	Day1-10
The derived plasma and urinary pharmacokinetic parameters for AZD1152 and AZD1152 hQPA The percentage of the [14C] AZD1152 dose recovered in urine, faeces and vomit (if presented), and the percentage of radioactive dose recovered overall.	Day1-10

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events (AEs), serious adverse events (SAEs) and deaths, Discontinuations for tolerability reasons, vital signs (temperature, blood pressure [BP], pulse rate and respiratory rate [RR])	AEs, SAEs, deaths, discontinuations ongoing to completion and vitals over 22 days - Screening, PD Day 1, Days 3, 6, 9, 14, 22
Electrocardiogram (ECG) parameters	Screening, PD Day 1, Day 4
Clinical chemistry, haematology (including clotting parameters) and urinalysis; physical examination	Chemistry/Heamatology - Screening, PD Day 1, Days 3, 6, 9, 14, 22Urinalysis - Screening, PD Day 1

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Mike Dennis, MD, The Christie Hospital, UK

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: November 23, 2009
• First Submitted That Met QC Criteria: November 23, 2009
• First Posted (Estimate): November 25, 2009

Study Record Updates

• Last Update Posted (Estimate): October 20, 2010
• Last Update Submitted That Met QC Criteria: October 19, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: Pharmacokinetics; AML; AZD1152; Acute Myeloid Leukaemia (AML)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: D1531C00012