A Study to Assess Safety, Tolerability and Pharmacokinetics of of AZD6553 in Healthy Volunteers and Patients With Chronic Obstructive Pulmonary Disease (COPD)

A Phase I, Randomised, Double-Blind, Placebo-Controlled, 3-Part Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Oral Doses of AZD6553 in Healthy Volunteers (Parts A and B) and Patients (Part C) With Chronic Obstructive Pulmonary Disease

AZD6553 is a new drug being developed as a possible treatment for patients with chronic obstructive pulmonary disease (COPD). COPD refers to chronic bronchitis and emphysema, a pair of two commonly co-existing diseases of the lungs in which the airways become inflamed and the small airsacs of the lungs become damaged. This leads to a limitation of the flow of air to and from the lungs causing shortness of breath. In contrast to asthma, the limitation of airflow is poorly reversible and usually gets progressively worse over time. There is an urgent medical need for therapies that could slow disease progression by targeting the underlying mechanisms associated with the changes in the lungs in patients with COPD. AZD6553 acts by reducing the activity of a protease found to be involved in the disease process in COPD. AZD6553 is being developed as a novel oral treatment to control the symptoms and exacerbations of COPD, and reduce the progression and severity of the disease. The purpose of this research study is to determine how safe and well-tolerated AZD6553 is and how much AZD6553 enters blood circulation by collecting blood and urine samples during the study. We are also investigating what AZD6553 is broken down into, when given orally, how much of the drug is cleared from the body via the kidneys, and the effect of taking the drug after food. This will all be done by analysis of blood and urine samples taken at various point during the study.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: AZD6553; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 109
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Parts A and B only; Body mass index (BMI) between 18 and 30 kg/m2.
• Parts A and B only; Normal physical examination, laboratory values, and vital signs (blood pressure and pulse) unless the investigator considers an abnormality to be clinically irrelevant.
• Part C only; clinical diagnosis of COPD for at least one year and Post-bronchodilator FEV1 30 - 80% predicted, FEV1/FVC ratio < 70%

Exclusion Criteria:

• Participation in any clinical study with an investigational drug or new formulation of a marketed drug in the 3 months prior to Visit 2, or participation in a method development study one month prior to Visit 1
• Part C only: An acute exacerbation or acute respiratory infection (upper or lower) in the 4 weeks prior to Visit 1 or Visit 2.
• Part C only: Concomitant diagnosis of significant pulmonary disease other than COPD, including symptomatic asthma, cystic fibrosis and allergic bronchopulmonary aspergillosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Drug: AZD6553; Single or multiple oral dose
Placebo Comparator: 2	Drug: Placebo; single or multiple oral dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety variables (adverse events, ECG's blood pressure, pulse, safety lab)	Part A Intensive sampling for 24 hours , frequent sampling up to 72 hours, Part B Frequent Sampling over 12 days with intensive sampling on Days 1-2 and 8-9
Pharmacokinetic variables:-Cmax, AUC, tmax and t1/2	Part A Intensive sampling for 24 hours , frequent sampling up to 72 hours, Part B Frequent Sampling over 12 days with intensive sampling on Days 1-2 and 8-9

Secondary Outcome Measures

Outcome Measure	Time Frame
Lung Function SVC, IC, FEV1, FVC	Part C Days 2, 7 and 14
Pharmacokinetic variables; Urine CLR	Part A Days 1 and 2, Part B, Days 1 and 2 and Days 8,9 and 10, and Part C Day 1 and Day 14

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Quintiles, Inc.
• Investigators: Principal Investigator: T G K Mant, FRCP (UK) FFPM, Quintiles Drug Research Unit at Guy's Hospital; Study Director: Joanna Marks-Konczalik, AstraZeneca R&D Charnwood

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: February 11, 2010
• First Submitted That Met QC Criteria: February 11, 2010
• First Posted (Estimate): February 12, 2010

Study Record Updates

• Last Update Posted (Estimate): September 24, 2010
• Last Update Submitted That Met QC Criteria: September 22, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: lung; COPD; Healthy Volunteers; Chronic; respiratory disease; placebo-controlled; obstructive; pulmonary; AZD6553; COPD Patients
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D2580C00001; 2009-016931-36 (EudraCT Number)