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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00430300
First received: January 30, 2007
Last updated: May 17, 2013
Last verified: May 2013
  Purpose

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


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: UK-432,097
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 6 [ Time Frame: Pre-dose at Baseline, Week 6 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2, 4 and 8 [ Time Frame: Pre-dose at Baseline, Week 2, 4, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Trough Forced Expiratory Volume in 6 Seconds (FEV6) at Week 2, 4, 6 and 8 [ Time Frame: Pre-dose at Baseline, Week 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Trough Forced Vital Capacity (FVC) at Week 2, 4, 6 and 8 [ Time Frame: Pre-dose at Baseline, Week 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Trough Inspiratory Capacity (IC) at Week 2, 4, 6 and 8 [ Time Frame: Pre-dose at Baseline, Week 2, 4, 6, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Post-Study Drug FEV1 at Week 2, 4, and 6 [ Time Frame: 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Post-Study Drug FEV6 at Week 2, 4, and 6 [ Time Frame: 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Post-Study Drug FVC at Week 2, 4, and 6 [ Time Frame: 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Post-Study Drug IC at Week 2, 4, and 6 [ Time Frame: 15 to 30 minutes post-dose at Baseline, Week 2, 4, 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Post-Bronchodilator FEV1 at Week 6 [ Time Frame: 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Post-Bronchodilator FEV6 at Week 6 [ Time Frame: 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Post-Bronchodilator FVC at Week 6 [ Time Frame: 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Post-Bronchodilator IC at Week 6 [ Time Frame: 15 to 30 minutes post-bronchodilator administration at Baseline, Week 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Dyspnea (Baseline Dyspnea Index/Transition Dyspnea Index [BDI/TDI]) at Week 2, 4, and 6 [ Time Frame: Baseline, Week 2, 4, 6 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Symptom Score at Week 1, 2, 3, 4, 5, 6, 7, and 8 [ Time Frame: Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Rescue Bronchodilator Use at Week 1, 2, 3, 4, 5, 6, 7, and 8 [ Time Frame: Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Morning and Evening Peak Expiratory Flow Rate (PEFR) at Week 1, 2, 3, 4, 5, 6, 7, and 8 [ Time Frame: Pre-dose at Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Categorical Scores on Clinical Global Impression of Change (CGI-C) [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With Categorical Scores on Patient Global Impression of Change (PGI-C) [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Change From Baseline in Pulse Rate at Week 0, 1, 2, 4, and 6 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in Blood Pressure at Week 0, 1, 2, 4, and 6 [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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).

  • Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate) at Week 0, 1, 2, 4, 6, and 8 [ Time Frame: 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) ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Pre-dose and 15 to 30 minutes Post-dose at Week 0, 1, 2, 4, 6 ] [ Designated as safety issue: No ]
    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.


Enrollment: 87
Study Start Date: January 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00430300

Locations
Australia, New South Wales
Pfizer Investigational Site
Camperdown, New South Wales, Australia, 2050
Pfizer Investigational Site
Glebe, New South Wales, Australia, 2037
Australia, South Australia
Pfizer Investigational Site
Daw Park, South Australia, Australia, 5041
Australia, Western Australia
Pfizer Investigational Site
Nedlands, Western Australia, Australia, 6009
Canada, Alberta
Pfizer Investigational Site
Calgary, Alberta, Canada, T1Y 6J4
Pfizer Investigational Site
Red Deer, Alberta, Canada, T4N 6V7
Canada, Ontario
Pfizer Investigational Site
Hamilton, Ontario, Canada, L8N 3Z5
Canada, Quebec
Pfizer Investigational Site
Québec, Quebec, Canada, G1V 4G5
Pfizer Investigational Site
Trois-Rivières, Quebec, Canada, G8T 7A1
Netherlands
Pfizer Investigational Site
Almelo, Netherlands, 7609 PP
Pfizer Investigational Site
Eindhoven, Netherlands, 5623 EJ
Pfizer Investigational Site
Zuthpen, Netherlands, 7207 BA
Poland
Pfizer Investigational Site
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
United Kingdom
Pfizer Investigational Site
Chertsey, Surrey, United Kingdom, KT16 0PZ
Pfizer Investigational Site
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
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00430300     History of Changes
Other Study ID Numbers: A3971013
Study First Received: January 30, 2007
Results First Received: May 17, 2013
Last Updated: May 17, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
Dry Powder for Inhalation
Chronic Obstructive Pulmonary Disease
Lung Function testing

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on July 20, 2014