Safety And Efficacy Of UK-432,097 In Chronic Obstructive Pulmonary Disease.

Study Overview
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Brief Summary
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Safety and efficacy (measured by spirometry) of UK-432,097 administration will be tested in patients with chronic obstructive pulmonary disease.

Official Title
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A Phase II, Randomized, Double Blind, Placebo Controlled, Parallel Group Study To Evaluate the Efficacy And Safety of UK-432,097 Dry Powder For Inhalation In Adults With Moderate To Severe Chronic Obstructive Pulmonary Disease.

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: UK-432,097
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis, for at least 6 months, of moderate to severe COPD (GOLD) and who meet the criteria for Stage II-III disease Patients must have a smoking history of at least 10 pack-years Patients must have stable disease for at least 1 month prior to screening. Exclusion Criteria: More than 2 exacerbations of COPD in the preceding year History of a lower respiratory tract infection or significant disease instability during the month proceding screening or during the time between screen and randomization. History or presence of respiratory failure, cor pulmonale or right ventricular failure

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 150mcg, 450mcg or 1350mcg<br>Active treatment given BID via a double pin monodose capsule inhaler device | Drug: UK-432,097<br>* Formulated as a dry powder, supplied as capsules and administered using an atomizer device. Given as either 150mcg, 450mcg or 1350mcg BID.<br>|
| Placebo Comparator: Placebo<br>Placebo treatment given BID via a single pin monodose inhaler device | Drug: Placebo<br>* Capsules containing 100% lactose administered BID using an atomizer device<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 6 | FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Trough FEV1 was obtained from spirometry, performed before study treatment administration. | Pre-dose at Baseline, Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 4 and 8 | FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Trough FEV1 was obtained from spirometry, performed before study treatment administration. | Pre-dose at Baseline, Week 2, 4, 8 | 
| Change From Baseline in Trough Forced Expiratory Volume in 6 Seconds (FEV6) at Week 2, 4, 6 and 8 | FEV6 is the maximal volume of air exhaled in the first 6 seconds of a forced expiration from a position of full inspiration. Trough FEV6 was obtained from spirometry, performed before study treatment administration. | Pre-dose at Baseline, Week 2, 4, 6, 8 | 
| Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 2, 4, 6 and 8 | FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Trough FVC was obtained from spirometry, performed before study treatment administration. | Pre-dose at Baseline, Week 2, 4, 6, 8 | 
| Change From Baseline in Trough Inspiratory Capacity (IC) at Week 2, 4, 6 and 8 | IC is the maximum volume of air that can be inhaled into the lungs from the normal resting position after breathing out normally. Trough IC was obtained from spirometry, performed before study treatment administration. | Pre-dose at Baseline, Week 2, 4, 6, 8 | 
| Change From Baseline in Post-Study Drug FEV1 at Week 2, 4, and 6 | FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Post-study drug FEV1 was obtained from spirometry, performed 15-30 minutes after study treatment administration. | 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6 | 
| Change From Baseline in Post-Study Drug FEV6 at Week 2, 4, and 6 | FEV6 is the maximal volume of air exhaled in the first 6 seconds of a forced expiration from a position of full inspiration. Post-study drug FEV6 was obtained from spirometry, performed 15-30 minutes after study treatment administration. | 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6 | 
| Change From Baseline in Post-Study Drug FVC at Week 2, 4, and 6 | FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Post-study drug FVC was obtained from spirometry, performed 15-30 minutes after study treatment administration. | 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6 | 
| Change From Baseline in Post-Study Drug IC at Week 2, 4, and 6 | IC is the maximum amount of air that can be inhaled into the lungs from the normal resting position after breathing out normally. Post-study drug IC was obtained from spirometry, performed 15-30 minutes after study treatment administration. | 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6 | 
| Change From Baseline in Post-Bronchodilator FEV1 at Week 6 | FEV1 is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration. Post-bronchodilator FEV1 was obtained from spirometry, performed 15-30 minutes after bronchodilator (salbutamol) administration. | 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6 | 
| Change From Baseline in Post-Bronchodilator FEV6 at Week 6 | FEV6 is the maximal volume of air exhaled in the first 6 seconds of a forced expiration from a position of full inspiration. Post-bronchodilator FEV6 was obtained from spirometry, performed 15-30 minutes after bronchodilator (salbutamol) administration. | 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6 | 
| Change From Baseline in Post-Bronchodilator FVC at Week 6 | FVC is the volume of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. Post-bronchodilator FVC was obtained from spirometry, performed 15-30 minutes after bronchodilator (salbutamol) administration. | 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6 | 
| Change From Baseline in Post-Bronchodilator IC at Week 6 | IC is the maximum volume of air that can be inhaled into the lungs from the normal resting position after breathing out normally. Post-bronchodilator IC was obtained from spirometry, performed 15-30 minutes after bronchodilator (salbutamol) administration. | 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6 | 
| Change From Baseline in Dyspnea (Baseline Dyspnea Index/Transition Dyspnea Index [BDI/TDI]) at Week 2, 4, and 6 | BDI: 24-item questionnaire to assess baseline dyspnea in 3 domains, functional impairment; magnitude of task; magnitude of effort. Each item rated on 5-point scale: 0 (very severe), 4 (no impairment). BDI total score range: 0 to 12, lower score=more severe dyspnea. TDI: 24-item questionnaire to measure changes in dyspnea severity from baseline in same 3 domains, as in BDI. Each item rated on 7-point scale: -3 (major deterioration) to 3 (major improvement). TDI total score range: -9 to 9, lower score=more deterioration. BDI/TDI total scores were obtained by adding scores for each of 3 domains. | Baseline, Week 2, 4, 6 | 
| Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 | COPD symptom score: participants rated the severity of their COPD symptoms (cough, breathlessness, and sputum production) in daily symptom dairy according to how they felt during the past 24 hours on a 4-point scale ranging from 0 (none) to 3 (severe). A participant's daily score for each symptom was averaged over each week. | Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8 | 
| Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 | Participants were issued with rescue medication (Salbutamol MDI [100 mcg/actuation]) and were instructed to use 1-2 puffs as required, as a rescue therapy. All rescue medication use was recorded in daily paper dairy by participant. A participant's daily use (puffs/day) was averaged over each week. | Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8 | 
| Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 | The PEFR is a participant's maximum speed of expiration, as measured with a peak flow meter. All participants were issued with a hand-held peak flow device and instructed to perform twice daily (morning and evening) prior to taking any medication. A participant's daily values were averaged over each week. | Pre-dose at Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8 | 
| Number of Participants With Categorical Scores on Clinical Global Impression of Change (CGI-C) | CGI-C: clinician's global impression of a participant's clinical condition in terms of change relative to the start of treatment. Rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected. | Week 6 | 
| Number of Participants With Categorical Scores on Patient Global Impression of Change (PGI-C) | PGI-C: participant rated instrument to measure participant's clinical condition in terms of change relative to the start of treatment. Rated on a 7-point scale from 1 (very much improved) to 7 (very much worse). Higher score = more affected. | Week 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry Powder for Inhalation, Chronic Obstructive Pulmonary Disease, Lung Function testing