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 - N/A

Phase 1

• Conditions: Chronic obstructive pulmonary disease (COPD).; MedDRA version: 8.1Level: LLTClassification code 10009033Term: Chronic obstructive pulmonary disease

• Registration Number: EUCTR2006-002578-23-NL

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2006-11-10
• Study Completion: 2008-07-16
• Last Update Posted: 8 August 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 600

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. Females of non-child-bearing potential will be defined as:
• Females over the age of 60 years.
• Females who are 40-60 years of age who have been amenorrheic for at least 2 years and have a serum FSH level >30 IU/L in the absence of hormone replacement therapy or have a documented hysterectomy.
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:
• Subjects must have a post-bronchodilator FEV1/FVC ratio < 0.7 and a postbronchodilator FEV1 of 30 - 80% (inclusive) of the predicted value for age, height, race and sex using European Community for Coal and Steel ECCS standards Luxembourg 1993). To qualify for randomization, these criteria must be met at screening and replicated during run-in phase (see randomization criteria for details).
3. Subjects must have a smoking history of at least 10 pack-years* and meet one of the following criteria:
• They are current smokers or
• They are ex-smokers who have abstained from smoking for at least 6 months.
*Formula for pack-years cigarettes = (average number of cigarettes/day ÷ 20) x years of smoking. Formula for pack-years tobacco = ounces per week x 2/7 x years of smoking.
4. Subjects must have stable disease for at least 1 month prior to screening. During the screening and run-in phase subjects must be able to manage disease symptoms adequately with short-acting bronchodilators only [i.e. inhaled ipratropium bromide 2 actuations (20µg /actuation) QID administered from a MDI +/- salbutamol (albuterol) rescue medication up to a maximum of 8 actuations (100µg /actuation) daily], without reliance on other therapies including oral or inhaled corticosteroids, long-acting bronchodilators, nebulizer therapy, theophylline or regular oxygen.
5. Body Mass Index (BMI) < 35 kg/m2 and a total body weight >40 kg.
6. Subjects must be able to give informed written consent prior to entering the study.
7. Subjects must be willing and able to comply with scheduled visit and all study related procedures.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

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 (either PRN or long term oxygen therapy, LTOT).
5. Any clearly documented history of adult asthma or other chronic respiratory disorders (e.g. bronchiectasis, pulmonary fibrosis, pneumoconiosis).
6. Known previous diagnosis of HIV infection (specific screening is not required).
7. History of cancer (other than cutaneous basal cell) in the previous 5 years.
8. 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 transientischemic attacks).
9. Active tuberculosis within the previous 2 years.
10. History within the previous 6 months of:
• An epileptic seizure.
• Poorly controlled Type 1 or Type 2 diabetes.
• Acute hepatitis of any aetiology.
11. A major surgical operation within 1 month of screening.
12. Screening systolic blood pressure < 90mmHg.
13. ECG abnormalities at screening or randomization, including those listed below. The investigator will decide whether ECG abnormalities other than those listed are clinically significant and should exclude the subject from enrolment:
• Predominant heart rhythm other than normal sinus rhythm e.g. atrial fibrillation, atrial flutter, supraventricular tachycardia.
• Subjects with pre-randomization evidence of QTc prolongation (defined as >450
msec for men; >470 msec for women) are not eligible for randomization. This assessment is made by the investigator at the time of ECG collection.
• Atrioventricular (AV) block greater than first degree.
• Resting heart rate >100 or <40 bpm.
• Evidence of previous myocardial infarction or significant ischemic changes in the absence of clinical history consistent with these findings.
14. History or evidence, based upon a complete medical history, full physical examination, posterior-anterior chest X-ray (within last 12 months), 12-lead resting ECG or clinical laboratory test results, of any other significant concomitant clinical disease that, in the opinion of the investigator, could interfere with the conduct, safety or interpretation of results of this study. Subjects with certain chronic conditions such as hypertension, thyroid disease, Type 1 or Type 2 diabetes, hypercholesterolemia, gastroesophageal reflux, or depression maybe included in the study as long as the conditions are well controlled and medications relating to the condition are stable and would not be predicted to compromise safety or interfere with the tests and interpretations of this study.
15. Positive HBsAg, HBcAB or anti-hepatitis C virus serology.
16. Liver function test abnormalities:
• Alanine amino transferase >1.5 x upper limit of normal (ULN).
• Aspartate amino transferase >1.5 x ULN.
• Alkaline phosphatase >1.2 x ULN.
• Total bilirubin >1.5 x ULN.
17. Use of any of the proh

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy and safety/tolerability of UK-432,097 DPI in adults with moderate to severe COPD (GOLD stage II/III).;Secondary Objective: 1. To explore the efficacious dose range for UK-432,097 DPI in COPD and provide information for Phase 2b dose ranging study(ies).<br>2. To evaluate the time course of response to UK-432,097 DPI.<br>3. To evaluate the washout / persistence of UK-432,097 DPI effects on lung function and symptoms for two weeks after stopping the drug.<br>4. To evaluate the PK-PD relationship between dose and/or systemic UK-432,097 exposure vs. efficacy and/or safety/tolerability in COPD subjects.<br>;Primary end point(s): Change from baseline in through (prior to administration of study drug) FEV1 at Week 6.