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

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.

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

Study Overview

• Status: Terminated
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: UK-432,097; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Pfizer Investigational Site
    • Glebe, New South Wales, Australia, 2037
      • Pfizer Investigational Site
  • South Australia
    • Daw Park, South Australia, Australia, 5041
      • Pfizer Investigational Site
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Pfizer Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T1Y 6J4
      • Pfizer Investigational Site
    • Red Deer, Alberta, Canada, T4N 6V7
      • Pfizer Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Pfizer Investigational Site
  • Quebec
    • Québec, Quebec, Canada, G1V 4G5
      • Pfizer Investigational Site
    • Trois-Rivières, Quebec, Canada, G8T 7A1
      • Pfizer Investigational Site
• Netherlands
  • Almelo, Netherlands, 7609 PP
    • Pfizer Investigational Site
  • Eindhoven, Netherlands, 5623 EJ
    • Pfizer Investigational Site
  • Zuthpen, Netherlands, 7207 BA
    • Pfizer Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-326
    • Pfizer Investigational Site
  • Gdansk, Poland, 80-952
    • Pfizer Investigational Site
  • Lodz, Poland, 90-153
    • Pfizer Investigational Site
  • Warszawa, Poland, 01-138
    • Pfizer Investigational Site
• United Kingdom
  • Leicester, United Kingdom, LE3 9QP
    • Pfizer Investigational Site
  • London, United Kingdom, E2 9ZY
    • Pfizer Investigational Site
  • Manchester, United Kingdom, M23 QZ
    • Pfizer Investigational Site
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Pfizer Investigational Site
  • Southampton, United Kingdom, SO16 6YD
    • Pfizer Investigational Site
  • Surrey
    • Chertsey, Surrey, United Kingdom, KT16 0PZ
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Pulse Rate at Week 0, 1, 2, 4, and 6	Pulse rate: the number of pulsations noted in a peripheral artery per unit of time after participant rested supine for 5 minutes, reported as beats per minute (bpm).	Baseline (pre-dose at Week 0); Pre-dose and 3-hour post-dose on Week 1, 6; 3-hour post-dose on Week 0, 2, 4
Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6	BP is the pressure of the blood within the arteries. It is produced primarily by the contraction of the heart muscle. BP measurement is recorded by 2 numbers: systolic BP (SBP, BP when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle) and diastolic BP (DBP, BP when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles). BP was measured by sphygmomanometer (manual or semi-automated) using appropriate-sized and calibrated cuff after participant rested in supine position for 5 minutes.	Baseline (pre-dose at Week 0); Pre-dose and 3-hour post-dose on Week 1, 6; 3-hour post-dose on Week 0, 2, 4
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (QT, QTc, QTcB, QTcF, QRS, RR and PR) at Week 0, 1, 2, 4, 6, and 8	Standard 12-lead ECG was performed after participant has rested for at least 10 minutes in supine position. ECG intervals (Int) included PR Int (time between onset of atrial depolarization and onset of ventricular depolarization), QRS Int (represented ventricular depolarization), RR Int (time between 2 QRS complex), QT Int (time corresponding to the beginning of depolarization to repolarization of the ventricles), corrected QT (QTc) Int, QT Int corrected by Fridericia's formula (QTcF=QT divided by cube root of RR Int) and Bazett's formula (QTcB=QT divided by square root of RR Int).	Baseline (pre-dose at Week 0); Pre-dose and 3-hour post-dose on Week 6; 3-hour post-dose on Week 0, 1, 2, 4; Week 8 (follow-up)
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate) at Week 0, 1, 2, 4, 6, and 8	Standard 12-lead ECG was performed after the participant has rested quietly for at least 10 minutes in supine position. The time interval between consecutive heart beats (RR interval) was used to calculate heart rate.	Baseline (pre-dose at Week 0); Pre-dose and 3-hour post-dose on Week 6; 3-hour post-dose on Week 0, 1, 2, 4; Week 8 (follow-up)
Change in Post-Study Drug Forced Expiratory Volume in 1 Second (FEV1) Compared to Pre-Study Drug Forced Expiratory Volume in 1 Second (FEV1) at Week 0, 1, 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. Pre-study drug FEV1 was obtained from spirometry, performed before study treatment administration.	Pre-dose and 15 to 30 minutes Post-dose at Week 0, 1, 2, 4, 6

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: January 30, 2007
• First Submitted That Met QC Criteria: January 31, 2007
• First Posted (Estimate): February 1, 2007

Study Record Updates

• Last Update Posted (Estimate): July 8, 2013
• Last Update Submitted That Met QC Criteria: May 17, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Chronic Obstructive Pulmonary Disease; Dry Powder for Inhalation; Lung Function testing
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: A3971013