Primary ObjectiveTo evaluate the efficacy and safety/tolerability of UK-432,097 DPI in adults with moderate to severe COPD (GOLD stage II/III).
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline in trough (prior to administration of study drug) FEV1 at
Week 6.
Secondary outcome
Efficacy:
•Change from baseline in trough FEV1, forced expiratory volume in 6 seconds
(FEV6), forced vital capacity (FVC) and inspiratory capacity (IC) at weeks 2
and 4 and at week 8 (2 weeks after the completion of therapy).
• Change from baseline in trough FEV6, FVC and IC at week 6.
• Change from baseline in post-study drug FEV1, FEV6, FVC, and IC at weeks 2, 4
and 6.
• Change from baseline in post-bronchodilator FEV1, FEV6, FVC, and IC at week 6.
• Change from baseline in dyspnea (BDI/TDI) at weeks 2, 4 and 6.
• Change from baseline of COPD symptoms, rescue bronchodilator use (per daily
diary) and peak expiratory flow rate (PEFR).
• Global impression of change (Clinician & Patient) at week 6.
Safety:
• Adverse events (AEs).
• Laboratory safety data.
• Change in vital signs (pulse & blood pressure) and ECG post study drug.
• Acute change in FEV1 post-study drug compared to pre-study drug.
Other:
• Population pharmacokinetics.
• Exploratory biomarkers (e.g. C reactive protein [CRP]).
Background summary
Options for pharmacological intervention in the treatment of COPD are limited.
Short-acting and long-acting bronchodilators from both the β2-agonist and
anti-cholinergic classes are available for the relief of bronchospasm
associated with COPD, however no therapeutic class has consistently been shown
to display anti-inflammatory properties across the spectrum of disease, with
the use of inhaled corticosteroids (ICS) indicated only for subjects who
frequently exacerbate, unlike in asthma where ICS are indicated for the
maintenance treatment in all but the mildest and most intermittent subjects.
The development of an effective anti-inflammatory agent for COPD capable of
maintaining clinical stability, optimally with attenuation in the rate of
decline of lung function, would constitute a major advance in disease
management.
UK-432,097 is an adenosine A2a receptor agonist that is being developed as an
inhaled antiinflammatory agent for COPD. Adenosine A2a receptors are found on a
range of human inflammatory cells including neutrophils and
monocytes/macrophages. As UK-432,097 has been shown to inhibit the release of
multiple neutrophil- and monocyte/macrophage - derived activation products from
human cells ex vivo, this suggests that UK-432,097 may be effective as an
anti-inflammatory agent for the treatment of COPD.
Study objective
Primary Objective
To evaluate the efficacy and safety/tolerability of UK-432,097 DPI in adults
with moderate to severe COPD (GOLD stage II/III).
Study design
This is a 6 week, randomized, double blind, placebo-controlled, parallel group
study to evaluate the efficacy and safety of UK-432,097 DPI in adult subjects
with moderate to severe COPD as defined by GOLD stages II-III.
The study comprises 9 clinic visits: a screening visit, 2 visits during the
run-in phase (week -2 and week -1), a baseline/randomization visit (week 0) at
the start of the double-blind treatment phase, 4 visits during the double-blind
treatment phase (weeks 1, 2, 4 and 6) and a follow up visit (week 8) following
a 2 week washout (run out) phase.
An interim analysis for efficacy will be performed based on the primary
endpoint, namely mean change from baseline in trough FEV1 at week 6.
This interim analysis will be triggered when approximately 80 subjects have
completed double-blind treatment and the study may be terminated at that stage
depending on a predefined stopping criteria based on futility
Intervention
Eligible subjects will be issued at screening with the short-acting
bronchodilators, ipratropium bromide and salbutamol (albuterol) MDIs [supplied
by Pfizer] and instructed in their use. These medications will be used
throughout the study from screening through to week 8 (follow-up) and will be
the only COPD medications allowed, with the exception of UK-432,097/placebo.
Study burden and risks
UK-432,097 is an adenosine A2a receptor agonist that is being developed as an
inhaled antiinflammatory agent for COPD.
The development of an effective anti-inflammatory agent for COPD capable of
maintaining clinical stability, optimally with attenuation in the rate of
decline of lung function, would constitute a major advance in disease
management.
The patient is asked to make the study visits and perform the study procedures
according to protocol. The time the visits take is about 15 hours for each
patient, for 9 study visits.
During these visits bloodsampling is done, ECGs are made and spirometries are
done. See page 8-11 of the protocol for an overview of all trial procedures.
During the study all patients will be treated with salbutamol and ipratropium
bromide. By randomisation will be determined whether a patient will be treated
additionally with UK432,097 or placebo
Rivium Westlaan 142
2909 LD Capelle aan den IJssel
Nederland
Rivium Westlaan 142
2909 LD Capelle aan den IJssel
Nederland
Listed location countries
Age
Inclusion criteria
1. Male or female subjects between, and including, the ages of 40 and 80 years. Females need to be of non-childbearing potential (criteria gespcificeerd).
2. Subjects with a diagnosis, for at least 6 months, of moderate to severe COPD (GOLD) and who meet the criteria for Stage II-III disease.
3. Subjects must have a smoking history of at least 10 pack-years* (criteria gespecificeerd).
4. Subjects must have stable disease for at least 1 month prior to screening.
5. Subjects must be able to give informed written consent prior to entering the study.
Exclusion criteria
1. More than 2 exacerbations of COPD requiring treatment with oral steroids in the
preceding year or hospitalization for the treatment of COPD within 3 months of screening or more than twice during the preceding year.
2. History of a lower respiratory tract infection or significant disease instability during the month preceding screening or during the time between screening and randomization.
3. History or presence of respiratory failure, cor pulmonale or right ventricular failure.
4. Subjects with home oxygen therapy.
5. Any clearly documented history of adult asthma or other chronic respiratory disorders (e.g. bronchiectasis, pulmonary fibrosis, pneumoconiosis).
6. History of cancer (other than cutaneous basal cell) in the previous 5 years.
7. History within the previous year of: myocardial infarction, cardiac arrhythmia (e.g. atrial fibrillation, paroxysmal atrial fibrillation, atrial flutter, supraventricular tachycardia, ventricular tachycardia), left ventricular failure, unstable angina, coronary angioplasty, coronary artery bypass grafting (CABG) or cerebrovascular accident (including transient ischemic attacks)
8. A major surgical operation within 1 month of screening.
9. Screening systolic blood pressure < 90mmHg.
10. ECG abnormalities at screening or randomization (criteria specified).
11. Liver function test abnormalities (criteria specified)
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-002578-23-NL |
| CCMO | NL14939.060.06 |