Dose-Ranging Study Of GSK233705B In Subjects With Chronic... | NCT00676052

NCT00676052

Status Module

Label	Type	Description	Intervention Names
Arm 1	Experimental	GSK233705 12.5mcg	Drug: GSK233705 12.5mcg
Arm 2	Experimental	GSK233705 25mcg	Drug: GSK233705 25mcg
Arm 3	Experimental	GSK233705 50mcg	Drug: GSK233705 50mcg
Arm 4	Experimental	GSK233705 100mcg	Drug: GSK233705 100mcg
Arm 5	Experimental	GSK233705 200mcg	Drug: GSK233705 200mcg
Arm 6	Placebo Comparator	Placebo	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
GSK233705 12.5mcg	Drug	Once daily via dry powder inhaler	Arm 1
GSK233705 25mcg

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29	The trough FEV1 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28. The Baseline FEV1 is the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose [time 0] on Day 1. Change from Baseline was calculated by subtracting the post-baseline assessment value from the Baseline value.	Baseline (pre-dose Day 1) and Day 29

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29	Weighted means serial FEV1 was derived by calculating the area under curve (AUC), and then dividing by the time interval over which the AUC was calculated. Baseline was defined at pre-dose Day 1. The weighted mean change from Baseline is the weighted mean minus Baseline. The AUC was calculated using the trapezoidal rule. For all post-dose observations, actual times that the spirometry measurements were conducted was used for the calculation. Pre-dose observations were counted as 0 hr observations - that is they had their time set to the time of dosing. The pre-dose value used for the calculation of the AUC was the mean of the two pre-dose observations (-30 and 0 min for Day 1 or 28). If one of these observations was missing, the remaining single pre-dose observation was used.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

A signed and dated written informed consent prior to study participation.
Male or female adults.

A female is eligible to enter and participate in this study if she is of:

non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who is post-menopausal; or child-bearing potential, has a negative pregnancy test at Visit 1/Visit 1A, and agrees to one of the protocol-specified acceptable contraceptive methods used consistently and correctly (i.e. according to the approved product label and the instructions of the physician for the duration of the study - Screening through follow-up contact)

40 to 80 years of age at Visit 1
An established clinical history of COPD
Current or previous cigarette smokers with a history of cigarette smoking of ≥ 10 pack-years 1.
A post-albuterol/salbutamol FEV1/FVC ratio of ≤0.70 and a post-albuterol/salbutamol FEV1 of ≥35 and ≤70% of predicted normal values

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

Women who are pregnant or lactating.
A current diagnosis of asthma.
Known respiratory disorders other than COPD including but not limited to α-1 antitrypsin deficiency as the underlying cause of COPD, active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease.
Any previous lung resection surgery (e.g., lung volume reduction surgery or lobectomy)
Clinically significant Chest X-ray or computed tomography (CT) scan abnormalities within 6 months prior to Visit 1 that are not believed to be due to COPD.
Use of oral corticosteroids or antibiotics for COPD within 6 weeks prior to Visit 1.
Hospitalization for COPD or pneumonia within 3 months prior to Visit 1.
Use of antibiotics for a lower respiratory tract infection within 30 days prior to Visit 1.
Clinically significant and uncontrolled cardiovascular, neurological, psychiatric, renal, gastro-intestinal, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities.
An abnormal and clinically significant 12-lead electrocardiogram (ECG) that results in active medical problem.
Positive for Hepatitis B or Hepatitis C at Visit 1.
A current malignancy or previous history of cancer in remission for <5 years prior to Visit 1
A history of allergy or hypersensitivity to ipratropium, tiotropium, or atropine and any of their derivatives, lactose/milk protein or magnesium stearate.
Medical diagnosis of narrow-angle glaucoma, prostatic hypertrophy or bladder neck obstruction that in the opinion of the study investigator would prevent use of an inhaled anticholingeric.
Medically unable to withhold albuterol/salbutamol for 6 hours prior to spirometry testing at each study visit or to withhold ipratropium (if applicable) for the 6-hour period prior to the first 3 study visits (ipratropium cannot be used after Visit 3).
Additional Medications: Unable to stop using certain medications such as bronchodilators and corticosteroids for the protocol-specified times prior to Visit 1 (the Investigator will discuss the specific medications)
Use of inhaled corticosteroids at a dose greater than 1000 mcg/day of fluticasone propionate or equivalent within 30 days prior to Visit 1.
Use of long-term oxygen therapy (LTOT) or supplemental oxygen required for greater than 12 hours a day. Oxygen use as needed is not exclusionary.
Clinically significant sleep apnea that requires continuous positive airway pressure (CPAP)
Use of regular nebulized therapy
Use of nocturnal positive pressure or non-invasive positive pressure ventilation (NIPPV)
Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1.
An investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the above who is involved in this study
History of psychiatric disease, intellectual deficiency, poor motivation, substance abuse in the two years prior to Visit 1 (including drug and alcohol), or other conditions, which will limit the validity of informed consent to participate in the study.
Use of GSK233705B in previous studies.

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Jasper	Alabama	35501	United States
GSK Investigational Site

PubMed Identifier	Type	Citation	Retractions
22329914	Derived	Bateman E, Feldman G, Kilbride S, Brooks J, Mehta R, Harris S, Maden C, Crater G. Efficacy and safety of the long-acting muscarinic antagonist GSK233705 delivered once daily in patients with COPD. Clin Respir J. 2012 Oct;6(4):248-57. doi: 10.1111/j.1752-699X.2011.00278.x. Epub 2012 Feb 13.

Label	URL
Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.	View source

ID	Type	URL	Comment
AC2110664	Annotated Case Report Form	View IPD

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Placebo	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive placebo administered once daily via a novel dry powder inhaler.
FG001	GSK233705B 12.5 mcg

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Placebo	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive placebo administered once daily via a novel dry powder inhaler.
BG001	GSK233705B 12.5 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 12.5 mcg administered once daily via a novel dry powder inhaler.
BG002	GSK233705B 25 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 25 mcg administered once daily via a novel dry powder inhaler.
BG003	GSK233705B 50 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 50 mcg administered once daily via a novel dry powder inhaler.
BG004	GSK233705B 100 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 100 mcg administered once daily via a novel dry powder inhaler.
BG005	GSK233705B 200 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 200 mcg administered once daily via a novel dry powder inhaler.
BG006	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Day 29

The trough FEV1 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 28. The Baseline FEV1 is the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose [time 0] on Day 1. Change from Baseline was calculated by subtracting the post-baseline assessment value from the Baseline value.

ITT Population. Last observation carried forward (LOCF) data has been presented.

Posted

Least Squares Mean

Standard Error

Liter

Baseline (pre-dose Day 1) and Day 29

ID	Title	Description
OG000	GSK233705B 12.5 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 12.5 mcg administered once daily via a novel dry powder inhaler.
OG001	GSK233705B 25 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 25 mcg administered once daily via a novel dry powder inhaler.
OG002	GSK233705B 50 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 50 mcg administered once daily via a novel dry powder inhaler.
OG003	GSK233705B 100 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 100 mcg administered once daily via a novel dry powder inhaler.
OG004	GSK233705B 200 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 200 mcg administered once daily via a novel dry powder inhaler.
OG005	Placebo	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive placebo administered once daily via a novel dry powder inhaler.

Units	Counts
Participants	OG00094 OG00194 OG00297 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.058± 0.0180 OG0010.088± 0.0180 OG0020.060± 0.0178 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG005		ANCOVA		0.009	Analysis performed using ANCOVA with covariates of Baseline, sex, age, smoking status, responsiveness stratum and treatment. Missing trough FEV1 data at Day 29 was imputed using LOCF.	Mean Difference (Net)	0.067			2-Sided	95	0.017	0.117					Superiority
OG001 OG005

Secondary

Change From Baseline in Weighted Mean for 0 to 24 Hours Serial FEV1 on Day 1 to 2 and 28 to 29

Weighted means serial FEV1 was derived by calculating the area under curve (AUC), and then dividing by the time interval over which the AUC was calculated. Baseline was defined at pre-dose Day 1. The weighted mean change from Baseline is the weighted mean minus Baseline. The AUC was calculated using the trapezoidal rule. For all post-dose observations, actual times that the spirometry measurements were conducted was used for the calculation. Pre-dose observations were counted as 0 hr observations - that is they had their time set to the time of dosing. The pre-dose value used for the calculation of the AUC was the mean of the two pre-dose observations (-30 and 0 min for Day 1 or 28). If one of these observations was missing, the remaining single pre-dose observation was used.

ITT Population. Participants with analyzable data on the indicated time point have been presented.

Posted

Least Squares Mean

Standard Error

Liter

Baseline (pre-dose Day 1) and Days 1 to 2, Days 28 to 29

ID	Title	Description
OG000	GSK233705B 12.5 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 12.5 mcg administered once daily via a novel dry powder inhaler.
OG001	GSK233705B 25 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 25 mcg administered once daily via a novel dry powder inhaler.

Secondary

Change From Baseline in Weighted Mean for 0 to 24 Hours Forced Vital Capacity (FVC) on Day 1 to 2 and 28 to 29

Weighted means serial FVC was derived by calculating the AUC, and then dividing by the time interval over which the AUC was calculated. Baseline was defined at pre-dose Day 1. The weighted mean change from Baseline is the weighted mean minus Baseline. The AUC was calculated using the trapezoidal rule. For all post-dose observations, actual times that the spirometry measurements were conducted was used for the calculation. Pre-dose observations were counted as 0 hr observations - that is they had their time set to the time of dosing. The pre-dose value used for the calculation of the AUC was the mean of the two pre-dose observations (-30 and 0 min for Day 1 or 28). If one of these observations was missing, the remaining single pre-dose observation was used.

ITT Population. Participants with analyzable data on the indicated time point have been presented.

Posted

Least Squares Mean

Standard Error

Liter

Baseline (pre-dose Day 1) and Days 1 to 2, Days 28 to 29

ID	Title	Description
OG000	GSK233705B 12.5 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 12.5 mcg administered once daily via a novel dry powder inhaler.
OG001	GSK233705B 25 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 25 mcg administered once daily via a novel dry powder inhaler.

Secondary

Change From Baseline in Clinic Visit Trough FVC on Day 29

The trough FVC is defined as the mean of the FVC values obtained 23 and 24 hours after dosing on Day 28. The Baseline FVC is the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose [time 0] on Day 1. Change from Baseline was calculated by subtracting the post-baseline assessment value from the Baseline value.

ITT Population. Participants with analyzable data on the indicated time point have been presented.

Posted

Least Squares Mean

Standard Error

Liter

Baseline (pre-dose Day 1) and Day 29

ID	Title	Description
OG000	GSK233705B 12.5 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 12.5 mcg administered once daily via a novel dry powder inhaler.
OG001	GSK233705B 25 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 25 mcg administered once daily via a novel dry powder inhaler.
OG002	GSK233705B 50 mcg

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive placebo administered once daily via a novel dry powder inhaler.	0	96	0	96	7	96
EG001	GSK233705B 12.5 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 12.5 mcg administered once daily via a novel dry powder inhaler.	0	95	0	95	4	95
EG002	GSK233705B 25 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 25 mcg administered once daily via a novel dry powder inhaler.	0	96	2	96	6	96
EG003	GSK233705B 50 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 50 mcg administered once daily via a novel dry powder inhaler.	0	97	1	97	9	97
EG004	GSK233705B 100 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 100 mcg administered once daily via a novel dry powder inhaler.	0	95	1	95	5	95
EG005	GSK233705B 200 mcg	Eligible participants completed a two week run-in period during which they received placebo once daily via the novel dry powder inhaler. After run-in period, participants were randomized to receive GSK233705B 200 mcg administered once daily via a novel dry powder inhaler.	1	97	1	97	3	97

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Colitis	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected95 at risk EG0021 affected96 at risk EG0030 affected97 at risk EG0040 affected95 at risk EG0050 affected97 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected95 at risk EG0020 affected96 at risk EG003
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 11.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected95 at risk EG0020 affected96 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 11.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected95 at risk EG0020 affected96 at risk EG003
Uterine leiomyoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 11.1	Systematic Assessment	EG0000 affected96 at risk EG0010 affected95 at risk EG0021 affected96 at risk EG003

ID	Term
D008173	Lung Diseases, Obstructive
D008171	Lung Diseases
D012140	Respiratory Tract Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms