Clinical trial NCT01068184: A Study to Assess Safety, Tolerability and Pharmacokinetics of of AZD6553 in Healthy Volunteers and Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: AZD6553
Chronic
obstructive
pulmonary
lung
respiratory disease
placebo-controlled
COPD
Healthy Volunteers
COPD Patients
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Quintiles, Inc.
First posted: 2010-02-12
Enrollment: 109
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Safety variables (adverse events, ECG's blood pressure, pulse, safety lab)
timeFrame: 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
measure: Pharmacokinetic variables:-Cmax, AUC, tmax and t1/2
timeFrame: 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 outcomes:
measure: Lung Function SVC, IC, FEV1, FVC
timeFrame: Part C Days 2, 7 and 14
measure: Pharmacokinetic variables; Urine CLR
timeFrame: 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
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Quintiles Drug Research Unit at Guy's Hospital
name: T G K Mant, FRCP (UK) FFPM
role: PRINCIPAL_INVESTIGATOR
affiliation: AstraZeneca R&D Charnwood
name: Joanna Marks-Konczalik
role: STUDY_DIRECTOR
References: