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GSK233705 is a high-affinity specific muscarinic receptor (mAChR) antagonist which is being developed for the treatment of chronic obstructive pulmonary disease. This is a randomised, double-blind, placebo-controlled, dose ascending, parallel group study to examine the safety, tolerability, pharmacokinetics and pharmacodynamics of twice daily inhaled doses of GSK233705B for 7 days, in COPD subjects.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK233705B | Drug |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. | Up to follow-up (approximately 45 days) |
| Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Blood pressure was measured subsequent to 12 lead electrocardiogram (ECG). Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7. | Up to Day 7 (24 hours post-dose) |
| Summary of Mean Heart Rate | Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7. | Up to Day 7 (24 hour post dose) |
| Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | Up to Day 7 (0-4 hour) |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma Concentrations of GSK233705 | Blood samples were collected at indicated time points. 12 hour pharmacokinetic (PK) sampling was before evening dose. | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose |
| Urine Concentrations of GSK233705 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Eindhoven | 5623 EJ | Netherlands | |||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | This study has not been published in the scientific literature. |
| 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 |
|---|---|---|---|
| AC2108378 | Statistical Analysis Plan | View IPD |
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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From 29 March 2007 to 11 October 2007, total of 23 participants with chronic obstructive pulmonary disease (COPD) were randomized at four centres in the Netherlands. DISKUS™ is registered product of GlaxoSmithKline.
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Participants entered into Cohort I received single inhaled dose of dry powder inhaler (DPI) of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) and was formulated with lactose only as a vehicle to make 12.5 milligrams (mg). |
| FG001 | GSK233705 50 µg Twice Daily | Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 micrograms (µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg. |
| FG002 | GSK233705 100 µg Twice Daily | Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| 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 | Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE) | An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. | All subject population included all available data on participants who had received at least one dose of study medication (including placebo). | Posted | Count of Participants | Participants | Up to follow-up (approximately 45 days) |
|
All AE and SAE were reported until he or she has completed the study (including any follow-up period). This included 28 days of screening and 17 days of treatment and follow-up (approximately 45).
All subjects population was used for reporting non-SAE and SAE.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue | General disorders | MedDRA version | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose | Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | Up to Day 7 (0-4 hour) |
| Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | Up to Day 7 (0-4 hour) |
| Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose | Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | Up to Day 7 (0-4 hour) |
| Number of Participants With Abnormal 12-lead ECG Findings | Single measurements were taken at all time points. The pre-dose values were classed as Baseline. Data for number of participants with normal, abnormal not clinically significant and abnormal clinically significant is presented. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7. | Up to Day 7 (24 hour post dose) |
| Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | Up to Day 7 (0-4 hour) |
| Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | Up to Day 7 (0-4 hour) |
| Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | It was assessed on 1, 2, 4, 9, 12 and 24 hours on Days 1 and 7. Also on Day 7, it was measured on 0 hour (Baseline). At all time points 3 measurements were taken and formal statistical analysis was carried out on the derived maximum readings. Data for adjusted mean is presented as least square mean. | Up to Day 7 (24-hour post dose) |
| Number of Participants Who Used Rescue Medication | Inhaled salbutamol was used as a rescue medication. Participants were required to keep a diary of their rescue medication (total number of salbutamol doses taken) over the entire 7-day treatment period. Diaries were reviewed by the Investigator when participants were admitted to the unit on Days 1, 2, 7 and 8. | Up to Day 7 |
| Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Clinical chemistry parameters included urea, potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, creatine kinase, chloride, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyltransferase (GGT), albumin, sodium, phosphorus inorganic, calcium, alkaline phosphatase (ALP) and total protein. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the potential clinical concern (PCI) is provided. | Up to Day 7 |
| Number of Participants With Abnormalities in Hematology Data of Clinical Concern | Hematology parameters included platelet count, red blood cell (RBC) count, mean corpuscular volume (MCV), total neutrophils, white blood cell (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the PCI is provided. | Up to Day 7 |
| Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urinalysis parameters included protein, blood, ketones, glucose, bilirubin, urobilinogen, leukocyte esterase, specific gravity, nitrites and pH. Sediment microscopy was performed only on urine samples showing an abnormality on the dipstick. Microscopy was performed for: WBC, RBC, hyaline casts, granular casts and cellular casts. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). | Up to Day 7 (pre dose) |
| Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Holter monitors were switched on immediately prior to dosing (up to 15mins pre-dose) so as to capture Holter ECG data from the 24 hour period following dosing. It was assessed on Day 1 and 7. | Up to Day 7 |
Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data is presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose. |
| Day 1 and 7 throughout 24 hours |
| Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning samples. | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose |
| Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning sample as adjusted geometric mean. | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose |
| Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples as adjusted geometric mean. | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose |
| Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples. | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose |
| Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as AM dose and PM dose. 12 hour pharmacokinetic sampling was before evening dose. | Day 1 and 7 throughout 24 hours |
| Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose. | Day 1 and 7 throughout 24 hours |
| Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr) | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study. 12 hour pharmacokinetic sampling was before evening dose. | Day 1 and 7 throughout 24 hours |
| Harderwijk |
| 3844 DG |
| Netherlands |
| GSK Investigational Site | Utrecht | 3584 CJ | Netherlands |
| GSK Investigational Site | Zuidlaren | 9471 GP | Netherlands |
For additional information about this study please refer to the GSK Clinical Study Register |
| AC2108378 | Clinical Study Report | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| AC2108378 | Dataset Specification | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| AC2108378 | Annotated Case Report Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| AC2108378 | Informed Consent Form | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| AC2108378 | Individual Participant Data Set | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| AC2108378 | Study Protocol | View IPD | For additional information about this study please refer to the GSK Clinical Study Register |
| BG001 | GSK233705 50 µg Twice Daily | Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg. |
| BG002 | GSK233705 100 µg Twice Daily | Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg. |
| BG003 | Total | Total of all reporting groups |
| Years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG000 | Placebo | Participants entered into Cohort I received single inhaled dose of DPI of matching placebo administered twice daily for 7 days and those in Cohort II received two inhaled dose of DPI matching placebo administered twice daily for 7 days. Matching placebo was administered via the DISKUS inhaler (60 doses) formulated with lactose only as a vehicle to make 12.5 mg. |
| OG001 | GSK233705 50 µg Twice Daily | Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg. |
| OG002 | GSK233705 100 µg Twice Daily | Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg. |
|
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| Primary | Summary of Mean Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Blood pressure was measured subsequent to 12 lead electrocardiogram (ECG). Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7. | All subject population was used. | Posted | Mean | Standard Deviation | Millimeters of mercury | Up to Day 7 (24 hours post-dose) |
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| Primary | Summary of Mean Heart Rate | Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7. | All subject population was used. | Posted | Mean | Standard Deviation | Beats per minute | Up to Day 7 (24 hour post dose) |
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| Primary | Maximum Value of SBP and DBP (0-4 Hour) for the Morning Dose | Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | All subject population | Posted | Least Squares Mean | 95% Confidence Interval | Millimeters of mercury | Up to Day 7 (0-4 hour) |
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| Primary | Maximum Value of Heart Rate (0-4 Hour) for the Morning Dose | Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | All subject population was used. | Posted | Least Squares Mean | 95% Confidence Interval | Beats per minute | Up to Day 7 (0-4 hour) |
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| Primary | Weighted Mean of SBP and DBP (0-4 Hour) for the Morning Dose | Blood pressure was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | All subject population was used. | Posted | Least Squares Mean | 95% Confidence Interval | Millimeters of mercury | Up to Day 7 (0-4 hour) |
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| Primary | Weighted Mean of Heart Rate (0-4 Hour) for the Morning Dose | Heart rate was measured subsequent to 12 lead ECG. Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | All subject population was used. | Posted | Least Squares Mean | 95% Confidence Interval | Beats per minute | Up to Day 7 (0-4 hour) |
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| Primary | Number of Participants With Abnormal 12-lead ECG Findings | Single measurements were taken at all time points. The pre-dose values were classed as Baseline. Data for number of participants with normal, abnormal not clinically significant and abnormal clinically significant is presented. It was assessed on Baseline (triplicate), 15, 30 minutes, 1.5, 4, 8 and 24 hours on Day 1 and 7. | All subject population was used. Only those participants available at the specified time points were analyzed. | Posted | Count of Participants | Participants | Up to Day 7 (24 hour post dose) |
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| Primary | Maximum Value (0-4 Hour) for the Morning Dose of ECG Parameters Corrected According to Fredericia's Formula (QTcF) and Corrected According to Bazett's Formula (QTc B) | Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | All subject population was used. | Posted | Least Squares Mean | 95% Confidence Interval | Milliseconds | Up to Day 7 (0-4 hour) |
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| Primary | Weighted Mean (0-4 h) for the Morning Dose of ECG Parameters QTcF and QTc B | Baseline was defined as the mean of the three planned pre-dose measurements. It was assessed on pre-dose, 15, 30 minutes, 1.5 and 4 hours on Day 1 and 7. Data for adjusted mean is presented as least square mean. | All subject population was used. | Posted | Least Squares Mean | 95% Confidence Interval | Milliseconds | Up to Day 7 (0-4 hour) |
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| Primary | Summary of Mean Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) | It was assessed on 1, 2, 4, 9, 12 and 24 hours on Days 1 and 7. Also on Day 7, it was measured on 0 hour (Baseline). At all time points 3 measurements were taken and formal statistical analysis was carried out on the derived maximum readings. Data for adjusted mean is presented as least square mean. | All subject population was used. | Posted | Least Squares Mean | 95% Confidence Interval | Liters | Up to Day 7 (24-hour post dose) |
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| Primary | Number of Participants Who Used Rescue Medication | Inhaled salbutamol was used as a rescue medication. Participants were required to keep a diary of their rescue medication (total number of salbutamol doses taken) over the entire 7-day treatment period. Diaries were reviewed by the Investigator when participants were admitted to the unit on Days 1, 2, 7 and 8. | All subject population was used. | Posted | Count of Participants | Participants | Up to Day 7 |
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| Primary | Number of Participants With Abnormalities in Chemistry Data of Clinical Concern | Clinical chemistry parameters included urea, potassium, aspartate aminotransferase (AST), total bilirubin, creatinine, creatine kinase, chloride, alanine aminotransferase (ALT), uric acid, glucose, gamma glutamyltransferase (GGT), albumin, sodium, phosphorus inorganic, calcium, alkaline phosphatase (ALP) and total protein. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the potential clinical concern (PCI) is provided. | All subject population was used. | Posted | Count of Participants | Participants | Up to Day 7 |
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| Primary | Number of Participants With Abnormalities in Hematology Data of Clinical Concern | Hematology parameters included platelet count, red blood cell (RBC) count, mean corpuscular volume (MCV), total neutrophils, white blood cell (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). Data for parameters with above and below the PCI is provided. | All subject population was used. | Posted | Count of Participants | Participants | Up to Day 7 |
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| Primary | Summary of Microscopy Data for Participants With Abnormal Urinalysis Dipstick Results | Urinalysis parameters included protein, blood, ketones, glucose, bilirubin, urobilinogen, leukocyte esterase, specific gravity, nitrites and pH. Sediment microscopy was performed only on urine samples showing an abnormality on the dipstick. Microscopy was performed for: WBC, RBC, hyaline casts, granular casts and cellular casts. It was assessed on Day 1 (pre-dose, 24 hours) and Day 7 (pre-dose, 24 hours). | All subject population was used. | Posted | Count of Participants | Participants | Up to Day 7 (pre dose) |
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| Primary | Summary of Mean (0-24 Hour) and Maximum (0-24 Hour) Heart Rate Measured Using 24 Hour Using Holter ECG Data | Holter monitors were switched on immediately prior to dosing (up to 15mins pre-dose) so as to capture Holter ECG data from the 24 hour period following dosing. It was assessed on Day 1 and 7. | All subject population was used. | Posted | Least Squares Mean | 95% Confidence Interval | Beats per minute | Up to Day 7 |
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| Secondary | Plasma Concentrations of GSK233705 | Blood samples were collected at indicated time points. 12 hour pharmacokinetic (PK) sampling was before evening dose. | PK population was used; this was defined as all participants in the all subjects population for whom a PK sample was obtained and analyzed. | Posted | Mean | Standard Deviation | Nanograms per milliliter | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose |
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| Secondary | Urine Concentrations of GSK233705 | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data is presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose. | PK population was used. | Posted | Mean | Standard Deviation | Nanograms per liter | Day 1 and 7 throughout 24 hours |
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| Secondary | Derived Plasma PK Parameters-area Under the Plasma Concentration-time Curve Over the Dosing Interval (AUC0-tau) | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning samples. | PK population was used. | Posted | Geometric Mean | Geometric Coefficient of Variation | Hour×Nanograms per milliliter | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose |
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| Secondary | Derived Plasma PK Parameters-area Under Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC0-t) | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning sample as adjusted geometric mean. | PK population was used. | Posted | Geometric Mean | 90% Confidence Interval | Hour×Nanograms per milliliter | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose |
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| Secondary | Derived PK Plasma Parameters-area Under Concentration-maximum Observed Plasma Concentration (Cmax) | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples as adjusted geometric mean. | PK population was used. | Posted | Geometric Mean | 90% Confidence Interval | Nanograms per liter | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose |
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| Secondary | Derived PK Plasma Parameters-area Under Concentration-time of Maximum Observed Plasma Concentration (T-max), Half-life (T-half) and Last Time Point Where the Concentration is Above the Limit of Quantification (T-last) | Blood samples were collected at indicated time points. 12 hour PK sampling was before evening dose. Data presented for morning and evening samples. | PK population was used. | Posted | Median | Full Range | Hour | Day 1 and 7 morning: pre-dose, 5, 15 minutes, 1, 6 and 12 hours post-dose and Day 1 and 7 evening: pre-dose, 5 and 30 post-dose |
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| Secondary | Derived Urine Pharmacokinetic (PK) Parameters-area Under the Plasma Concentration-amount of Drug Excreted Unchanged in Urine (Ae) | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as AM dose and PM dose. 12 hour pharmacokinetic sampling was before evening dose. | PK population was used. | Posted | Geometric Mean | Geometric Coefficient of Variation | Nanogram | Day 1 and 7 throughout 24 hours |
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|
|
| Secondary | Derived Urine PK Parameters-area Under Concentration-fraction of Dose Excreted Unchanged in Urine (Fe) | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study and consolidated data presented as 0-12 hours and 12-24 hours. 12 hour pharmacokinetic sampling was before evening dose. | PK population was used. | Posted | Mean | Standard Deviation | Percentage of dose | Day 1 and 7 throughout 24 hours |
|
|
|
| Secondary | Derived Urine PK Parameters-area Under Concentration-renal Clearance (Clr) | Urine GSK233705 pharmacokinetic excretion rate-time data is presented. Urine samples were collected throughout study. 12 hour pharmacokinetic sampling was before evening dose. | PK population was used. Only those participants available at the specified time points were analyzed. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liters per hour | Day 1 and 7 throughout 24 hours |
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 4 |
| 6 |
| EG001 | GSK233705 50 µg Twice Daily | Participants entered into Cohort I received single inhaled dose of DPI of GSK233705 50 µg administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg. | 0 | 9 | 0 | 9 | 4 | 9 |
| EG002 | GSK233705 100 µg Twice Daily | Participants entered into Cohort II received two inhaled dose of DPI GSK233705 (50 µg) administered twice daily for 7 days. GSK233705 50 μg blister was administered via the DISKUS inhaler (60 doses) and was formulated with magnesium stearate (0.5%) as a vehicle to make 12.5 mg. | 0 | 8 | 0 | 8 | 4 | 8 |
| Catheter site related reaction | General disorders | MedDRA version | Systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA version | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA version | Systematic Assessment |
|
| Infusion site irritation | General disorders | MedDRA version | Systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA version | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA version | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA version | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA version | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA version | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA version | Systematic Assessment |
|
| Dyspnoea exertional | Respiratory, thoracic and mediastinal disorders | MedDRA version | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA version | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA version | Systematic Assessment |
|
| Dry mouth | Gastrointestinal disorders | MedDRA version | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA version | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA version | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version | Systematic Assessment |
|
| Bursitis | Musculoskeletal and connective tissue disorders | MedDRA version | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA version | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA version | Systematic Assessment |
|
| Eye pruritus | Eye disorders | MedDRA version | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA version | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA version | Systematic Assessment |
|
| Pruritus allergic | Skin and subcutaneous tissue disorders | MedDRA version | Systematic Assessment |
|
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
|
| SBP, Day 1, 30 minutes |
|
| SBP, Day 1, 1.5 hour |
|
| SBP, Day 1, 4 hour |
|
| SBP, Day 1, 8 hour |
|
| SBP, Day 1, 24 hour |
|
| SBP, Day 7, Baseline |
|
| SBP, Day 7, 15 minutes |
|
| SBP, Day 7, 30 minutes |
|
| SBP, Day 7, 1.5 hour |
|
| SBP, Day 7, 4 hour |
|
| SBP, Day 7, 8 hour |
|
| SBP, Day 7, 24 hour |
|
| DBP, Day 1, Baseline |
|
| DBP, Day 1, 15 minutes |
|
| DBP, Day 1, 30 minutes |
|
| DBP, Day 1, 1.5 hour |
|
| DBP, Day 1, 4 hour |
|
| DBP, Day 1, 8 hour |
|
| DBP, Day 1, 24 hour |
|
| DBP, Day 7, Baseline |
|
| DBP, Day 7, 15 minutes |
|
| DBP, Day 7, 30 minutes |
|
| DBP, Day 7, 1.5 hour |
|
| DBP, Day 7, 4 hour |
|
| DBP, Day 7, 8 hour |
|
| DBP, Day 7, 24 hour |
|
|
| Day 1, 30 minutes |
|
| Day 1, 1.5 hour |
|
| Day 1, 4 hour |
|
| Day 1, 8 hour |
|
| Day 1, 24 hour |
|
| Day 7, Baseline |
|
| Day 7, 15 minutes |
|
| Day 7, 30 minutes |
|
| Day 7, 1.5 hour |
|
| Day 7, 4 hour |
|
| Day 7, 8 hour |
|
| Day 7, 24 hour |
|
|
| DBP, Day 1 |
|
| DBP, Day 7 |
|
| Mean Difference (Net) |
| -4.10 |
| Standard Error of the Mean |
| 4.215 |
| 2-Sided |
| 95 |
| -12.92 |
| 4.72 |
Comparison of SBP Day 7. |
| Superiority or Other |
| Mean Difference (Net) | 6.21 | Standard Error of the Mean | 5.727 | 2-Sided | 95 | -5.78 | 18.19 | Comparison of SBP Day 1. | Superiority or Other |
| Mean Difference (Net) | -4.76 | Standard Error of the Mean | 4.314 | 2-Sided | 95 | -13.79 | 4.27 | Comparison of SBP Day 7. | Superiority or Other |
| Mean Difference (Net) | 0.58 | Standard Error of the Mean | 2.138 | 2-Sided | 95 | -3.89 | 5.06 | Comparison of DBP Day 1. | Superiority or Other |
| Mean Difference (Net) | -6.64 | Standard Error of the Mean | 2.382 | 2-Sided | 95 | -11.62 | -1.65 | Comparison of DBP Day 7. | Superiority or Other |
| Mean Difference (Net) | 0.98 | Standard Error of the Mean | 2.248 | 2-Sided | 95 | -3.73 | 5.68 | Comparison of DBP Day 1. | Superiority or Other |
| Mean Difference (Net) | -10.81 | Standard Error of the Mean | 2.504 | 2-Sided | 95 | -16.05 | -5.57 | Comparison of DBP Day 7. | Superiority or Other |
|
| Mean Difference (Net) |
| 2.62 |
| Standard Error of the Mean |
| 3.785 |
| 2-Sided |
| 95 |
| -5.30 |
| 10.54 |
Comparison at Day 7. |
| Superiority or Other |
| Mean Difference (Net) | 0.16 | Standard Error of the Mean | 3.979 | 2-Sided | 95 | -8.17 | 8.48 | Comparison at Day 1. | Superiority or Other |
| Mean Difference (Net) | -5.44 | Standard Error of the Mean | 4.021 | 2-Sided | 95 | -13.86 | 2.97 | Comparison at Day 7. | Superiority or Other |
|
| DBP, Day 1 |
|
| DBP, Day 7 |
|
| Mean Difference (Net) |
| -1.88 |
| Standard Error of the Mean |
| 3.913 |
| 2-Sided |
| 95 |
| -10.07 |
| 6.31 |
Comparison of SBP Day 7. |
| Superiority or Other |
| Mean Difference (Net) | 3.01 | Standard Error of the Mean | 4.718 | 2-Sided | 95 | -6.87 | 12.88 | Comparison of SBP Day 1. | Superiority or Other |
| Mean Difference (Net) | -3.50 | Standard Error of the Mean | 4.005 | 2-Sided | 95 | -11.88 | 4.89 | Comparison of SBP Day 7. | Superiority or Other |
| Mean Difference (Net) | -0.28 | Standard Error of the Mean | 1.822 | 2-Sided | 95 | -4.09 | 3.54 | Comparison of DBP Day 1. | Superiority or Other |
| Mean Difference (Net) | -3.89 | Standard Error of the Mean | 2.116 | 2-Sided | 95 | -8.32 | 0.54 | Comparison of DBP Day 7. | Superiority or Other |
| Mean Difference (Net) | -1.75 | Standard Error of the Mean | 1.916 | 2-Sided | 95 | -5.76 | 2.26 | Comparison of DBP Day 1. | Superiority or Other |
| Mean Difference (Net) | -9.39 | Standard Error of the Mean | 2.224 | 2-Sided | 95 | -14.04 | -4.73 | Comparison of DBP Day 7. | Superiority or Other |
|
| Mean Difference (Net) |
| 2.39 |
| Standard Error of the Mean |
| 2.813 |
| 2-Sided |
| 95 |
| -3.50 |
| 8.28 |
Comparison at Day 7. |
| Superiority or Other |
| Mean Difference (Net) | -2.67 | Standard Error of the Mean | 2.869 | 2-Sided | 95 | -8.67 | 3.34 | Comparison at Day 1. | Superiority or Other |
| Mean Difference (Net) | -3.84 | Standard Error of the Mean | 2.989 | 2-Sided | 95 | -10.10 | 2.41 | Comparison at Day 7. | Superiority or Other |
| Abnormal not clinically significant |
|
| Abnormal clinically significant |
|
| Day 1, 15 minutes |
|
|
| Day 1, 30 minutes |
|
|
| Day 1, 1.5 hour |
|
|
| Day 1, 4 hour |
|
|
| Day 1, 8 hour |
|
|
| Day 1, 24 hour |
|
|
| Day 7, Baseline |
|
|
| Day 7, 15 minutes |
|
|
| Day 7, 30 minutes |
|
|
| Day 7, 1.5 hour |
|
|
| Day 7, 4 hour |
|
|
| Day 7, 8 hour |
|
|
| Day 7, 24 hour |
|
|
|
| QTcF, Day 1 |
|
| QTcF, Day 7 |
|
| Mean Difference (Net) |
| 9.02 |
| Standard Error of the Mean |
| 6.760 |
| 2-Sided |
| 95 |
| -5.13 |
| 23.17 |
Comparison of QTcB Day 7. |
| Superiority or Other |
| Mean Difference (Net) | 10.57 | Standard Error of the Mean | 8.510 | 2-Sided | 95 | -7.24 | 28.38 | Comparison of QTcB Day 1. | Superiority or Other |
| Mean Difference (Net) | 16.50 | Standard Error of the Mean | 7.052 | 2-Sided | 95 | 1.74 | 31.26 | Comparison of QTcB Day 7. | Superiority or Other |
| Mean Difference (Net) | 2.13 | Standard Error of the Mean | 8.908 | 2-Sided | 95 | -16.51 | 20.78 | Comparison of QTcF Day 1. | Superiority or Other |
| Mean Difference (Net) | 12.29 | Standard Error of the Mean | 5.298 | 2-Sided | 95 | 1.20 | 23.38 | Comparison of QTcF Day 7. | Superiority or Other |
| Mean Difference (Net) | 17.66 | Standard Error of the Mean | 9.171 | 2-Sided | 95 | -1.53 | 36.85 | Comparison of QTcF Day 1. | Superiority or Other |
| Mean Difference (Net) | 22.32 | Standard Error of the Mean | 5.454 | 2-Sided | 95 | 10.90 | 33.73 | Comparison of QTcF Day 7. | Superiority or Other |
|
| QTcF, Day 1 |
|
| QTcF, Day 7 |
|
| Mean Difference (Net) |
| 8.39 |
| Standard Error of the Mean |
| 5.902 |
| 2-Sided |
| 95 |
| -3.97 |
| 20.74 |
Comparison of QTcB Day 7. |
| Superiority or Other |
| Mean Difference (Net) | 11.47 | Standard Error of the Mean | 5.490 | 2-Sided | 95 | -0.02 | 22.96 | Comparison of QTcB Day 1. | Superiority or Other |
| Mean Difference (Net) | 15.28 | Standard Error of the Mean | 6.157 | 2-Sided | 95 | 2.39 | 28.17 | Comparison of QTcB Day 7. | Superiority or Other |
| Mean Difference (Net) | 8.32 | Standard Error of the Mean | 4.622 | 2-Sided | 95 | -1.35 | 18.00 | Comparison of QTcF Day 1. | Superiority or Other |
| Mean Difference (Net) | 8.75 | Standard Error of the Mean | 5.239 | 2-Sided | 95 | -2.21 | 19.72 | Comparison of QTcF Day 7. | Superiority or Other |
| Mean Difference (Net) | 16.83 | Standard Error of the Mean | 4.759 | 2-Sided | 95 | 6.87 | 26.79 | Comparison of QTcF Day 1. | Superiority or Other |
| Mean Difference (Net) | 20.46 | Standard Error of the Mean | 5.394 | 2-Sided | 95 | 9.17 | 31.75 | Comparison of QTcF Day 7. | Superiority or Other |
|
| FEV1, Day 1, 4 hour |
|
| FEV1, Day 1, 9 hour |
|
| FEV1, Day 1, 12 hour |
|
| FEV1, Day 1, 24 hour |
|
| FEV1, Day 7, Baseline |
|
| FEV1, Day 7, 1 hour |
|
| FEV1, Day 7, 2 hour |
|
| FEV1, Day 7, 4 hour |
|
| FEV1, Day 7, 9 hour |
|
| FEV1, Day 7, 12 hour |
|
| FEV1, Day 7, 24 hour |
|
| FVC, Day 1, 1 hour |
|
| FVC, Day 1, 2 hour |
|
| FVC, Day 1, 4 hour |
|
| FVC, Day 1, 9 hour |
|
| FVC, Day 1, 12 hour |
|
| FVC, Day 1, 24 hour |
|
| FVC, Day 7, Baseline |
|
| FVC, Day 7, 1 hour |
|
| FVC, Day 7, 2 hour |
|
| FVC, Day 7, 4 hour |
|
| FVC, Day 7, 9 hour |
|
| FVC, Day 7, 12 hour |
|
| FVC, Day 7, 24 hour |
|
| Mean Difference (Net) |
| 0.171 |
| Standard Error of the Mean |
| 0.0944 |
| 2-Sided |
| 95 |
| -0.015 |
| 0.357 |
Comparison of FEV1, Day 1, 2 hour |
| Superiority or Other |
| Mean Difference (Net) | 0.060 | Standard Error of the Mean | 0.0850 | 2-Sided | 95 | -0.107 | 0.228 | Comparison of FEV1, Day 1, 4 hour | Superiority or Other |
| Mean Difference (Net) | 0.150 | Standard Error of the Mean | 0.1195 | 2-Sided | 95 | -0.085 | 0.386 | Comparison of FEV1, Day 1, 9 hour | Superiority or Other |
| Mean Difference (Net) | 0.124 | Standard Error of the Mean | 0.1107 | 2-Sided | 95 | -0.094 | 0.343 | Comparison of FEV1, Day 1, 12 hour | Superiority or Other |
| Mean Difference (Net) | 0.163 | Standard Error of the Mean | 0.1220 | 2-Sided | 95 | -0.077 | 0.404 | Comparison of FEV1, Day 1, 24 hour | Superiority or Other |
| Mean Difference (Net) | 0.236 | Standard Error of the Mean | 0.1057 | 2-Sided | 95 | 0.027 | 0.444 | Comparison of FEV1, Day 7, Baseline | Superiority or Other |
| Mean Difference (Net) | 0.229 | Standard Error of the Mean | 0.1292 | 2-Sided | 95 | -0.026 | 0.483 | Comparison of FEV1, Day 7, 1 hour | Superiority or Other |
| Mean Difference (Net) | 0.095 | Standard Error of the Mean | 0.1309 | 2-Sided | 95 | -0.163 | 0.353 | Comparison of FEV1, Day 7, 2 hour | Superiority or Other |
| Mean Difference (Net) | 0.173 | Standard Error of the Mean | 0.1243 | 2-Sided | 95 | -0.072 | 0.418 | Comparison of FEV1, Day 7, 4 hour | Superiority or Other |
| Mean Difference (Net) | 0.205 | Standard Error of the Mean | 0.1499 | 2-Sided | 95 | -0.090 | 0.501 | Comparison of FEV1, Day 7, 9 hour | Superiority or Other |
| Mean Difference (Net) | 0.220 | Standard Error of the Mean | 0.1430 | 2-Sided | 95 | -0.062 | 0.502 | Comparison of FEV1, Day 7, 12 hour | Superiority or Other |
| Mean Difference (Net) | 0.206 | Standard Error of the Mean | 0.1520 | 2-Sided | 95 | -0.093 | 0.506 | Comparison of FEV1, Day 7, 24 hour | Superiority or Other |
| Mean Difference (Net) | 0.206 | Standard Error of the Mean | 0.0970 | 2-Sided | 95 | 0.015 | 0.397 | Comparison of FEV1, Day 1, 1 hour | Superiority or Other |
| Mean Difference (Net) | 0.329 | Standard Error of the Mean | 0.0994 | 2-Sided | 95 | 0.133 | 0.525 | Comparison of FEV1, Day 1, 2 hour | Superiority or Other |
| Mean Difference (Net) | 0.266 | Standard Error of the Mean | 0.0895 | 2-Sided | 95 | 0.090 | 0.443 | Comparison of FEV1, Day 1, 4 hour | Superiority or Other |
| Mean Difference (Net) | 0.320 | Standard Error of the Mean | 0.1258 | 2-Sided | 95 | 0.072 | 0.568 | Comparison of FEV1, Day 1, 9 hour | Superiority or Other |
| Mean Difference (Net) | 0.172 | Standard Error of the Mean | 0.1165 | 2-Sided | 95 | -0.058 | 0.402 | Comparison of FEV1, Day 1, 12 hour | Superiority or Other |
| Mean Difference (Net) | 0.154 | Standard Error of the Mean | 0.1285 | 2-Sided | 95 | -0.099 | 0.407 | Comparison of FEV1, Day 1, 24 hour | Superiority or Other |
| Mean Difference (Net) | 0.256 | Standard Error of the Mean | 0.1113 | 2-Sided | 95 | 0.036 | 0.475 | Comparison of FEV1, Day 7, Baseline | Superiority or Other |
| Mean Difference (Net) | 0.296 | Standard Error of the Mean | 0.1361 | 2-Sided | 95 | 0.027 | 0.564 | Comparison of FEV1, Day 7, 1 hour | Superiority or Other |
| Mean Difference (Net) | 0.202 | Standard Error of the Mean | 0.1378 | 2-Sided | 95 | -0.069 | 0.474 | Comparison of FEV1, Day 7, 2 hour | Superiority or Other |
| Mean Difference (Net) | 0.207 | Standard Error of the Mean | 0.1309 | 2-Sided | 95 | -0.051 | 0.465 | Comparison of FEV1, Day 7, 4 hour | Superiority or Other |
| Mean Difference (Net) | 0.280 | Standard Error of the Mean | 0.1579 | 2-Sided | 95 | -0.032 | 0.591 | Comparison of FEV1, Day 7, 9 hour | Superiority or Other |
| Mean Difference (Net) | 0.193 | Standard Error of the Mean | 0.1506 | 2-Sided | 95 | -0.104 | 0.490 | Comparison of FEV1, Day 7, 12 hour | Superiority or Other |
| Mean Difference (Net) | 0.180 | Standard Error of the Mean | 0.1601 | 2-Sided | 95 | -0.136 | 0.495 | Comparison of FEV1, Day 7, 24 hour | Superiority or Other |
| Mean Difference (Net) | 0.137 | Standard Error of the Mean | 0.2029 | 2-Sided | 95 | -0.263 | 0.537 | Comparison of FVC, Day 1, 1 hour | Superiority or Other |
| Mean Difference (Net) | 0.131 | Standard Error of the Mean | 0.1965 | 2-Sided | 95 | -0.257 | 0.518 | Comparison of FVC, Day 1, 2 hour | Superiority or Other |
| Mean Difference (Net) | -0.038 | Standard Error of the Mean | 0.1908 | 2-Sided | 95 | -0.414 | 0.338 | Comparison of FVC, Day 1, 4 hour | Superiority or Other |
| Mean Difference (Net) | 0.060 | Standard Error of the Mean | 0.2013 | 2-Sided | 95 | -0.337 | 0.457 | Comparison of FVC, Day 1, 9 hour | Superiority or Other |
| Mean Difference (Net) | 0.115 | Standard Error of the Mean | 0.2322 | 2-Sided | 95 | -0.343 | 0.572 | Comparison of FVC, Day 1, 12 hour | Superiority or Other |
| Mean Difference (Net) | 0.115 | Standard Error of the Mean | 0.1988 | 2-Sided | 95 | -0.277 | 0.507 | Comparison of FVC, Day 1, 24 hour | Superiority or Other |
| Mean Difference (Net) | 0.362 | Standard Error of the Mean | 0.2801 | 2-Sided | 95 | -0.190 | 0.914 | Comparison of FVC, Day 7, Baseline | Superiority or Other |
| Mean Difference (Net) | 0.269 | Standard Error of the Mean | 0.2696 | 2-Sided | 95 | -0.263 | 0.800 | Comparison of FVC, Day 7, 1 hour | Superiority or Other |
| Mean Difference (Net) | 0.021 | Standard Error of the Mean | 0.2648 | 2-Sided | 95 | -0.501 | 0.543 | Comparison of FVC, Day 7, 2 hour | Superiority or Other |
| Mean Difference (Net) | 0.177 | Standard Error of the Mean | 0.2606 | 2-Sided | 95 | -0.337 | 0.691 | Comparison of FVC, Day 7, 4 hour | Superiority or Other |
| Mean Difference (Net) | 0.266 | Standard Error of the Mean | 0.2684 | 2-Sided | 95 | -0.263 | 0.795 | Comparison of FVC, Day 7, 9 hour | Superiority or Other |
| Mean Difference (Net) | 0.367 | Standard Error of the Mean | 0.2923 | 2-Sided | 95 | -0.209 | 0.943 | Comparison of FVC, Day 7, 12 hour | Superiority or Other |
| Mean Difference (Net) | 0.242 | Standard Error of the Mean | 0.2665 | 2-Sided | 95 | -0.283 | 0.768 | Comparison of FVC, Day 7, 24 hour | Superiority or Other |
| Mean Difference (Net) | 0.152 | Standard Error of the Mean | 0.2106 | 2-Sided | 95 | -0.263 | 0.567 | Comparison of FVC, Day 1, 1 hour | Superiority or Other |
| Mean Difference (Net) | 0.321 | Standard Error of the Mean | 0.2039 | 2-Sided | 95 | -0.081 | 0.723 | Comparison of FVC, Day 1, 2 hour | Superiority or Other |
| Mean Difference (Net) | 0.311 | Standard Error of the Mean | 0.1981 | 2-Sided | 95 | -0.079 | 0.701 | Comparison of FVC, Day 1, 4 hour | Superiority or Other |
| Mean Difference (Net) | 0.348 | Standard Error of the Mean | 0.2090 | 2-Sided | 95 | -0.064 | 0.760 | Comparison of FVC, Day 1, 9 hour | Superiority or Other |
| Mean Difference (Net) | 0.245 | Standard Error of the Mean | 0.2410 | 2-Sided | 95 | -0.230 | 0.720 | Comparison of FVC, Day 1, 12 hour | Superiority or Other |
| Mean Difference (Net) | 0.162 | Standard Error of the Mean | 0.2063 | 2-Sided | 95 | -0.245 | 0.569 | Comparison of FVC, Day 1, 24 hour | Superiority or Other |
| Mean Difference (Net) | 0.535 | Standard Error of the Mean | 0.2907 | 2-Sided | 95 | -0.038 | 1.108 | Comparison of FVC, Day 7, Baseline | Superiority or Other |
| Mean Difference (Net) | 0.623 | Standard Error of the Mean | 0.2798 | 2-Sided | 95 | 0.072 | 1.175 | Comparison of FVC, Day 7, 1 hour | Superiority or Other |
| Mean Difference (Net) | 0.459 | Standard Error of the Mean | 0.2748 | 2-Sided | 95 | -0.083 | 1.000 | Comparison of FVC, Day 7, 2 hour | Superiority or Other |
| Mean Difference (Net) | 0.464 | Standard Error of the Mean | 0.2705 | 2-Sided | 95 | -0.069 | 0.997 | Comparison of FVC, Day 7, 4 hour | Superiority or Other |
| Mean Difference (Net) | 0.445 | Standard Error of the Mean | 0.2786 | 2-Sided | 95 | -0.104 | 0.994 | Comparison of FVC, Day 7, 9 hour | Superiority or Other |
| Mean Difference (Net) | 0.284 | Standard Error of the Mean | 0.3034 | 2-Sided | 95 | -0.314 | 0.882 | Comparison of FVC, Day 7, 12 hour | Superiority or Other |
| Mean Difference (Net) | 0.384 | Standard Error of the Mean | 0.2766 | 2-Sided | 95 | -0.162 | 0.929 | Comparison of FVC, Day 7, 24 hour | Superiority or Other |
| Title | Measurements |
|---|---|
|
| Inorganic phosphorus, High |
|
|
| Urine microscopy-WBC-Day 1 |
|
| Urine microscopy-WBC-Day 7 |
|
| Maximum heart rate, Day 7 |
|
| Mean heart rate, Day 1 |
|
| Mean heart rate, Day 7 |
|
| Mean Difference (Net) |
| 5.730 |
| Standard Error of the Mean |
| 8.0907 |
| 2-Sided |
| 95 |
| -11.200 |
| 22.664 |
Comparison of maximum heart rate Day 7. |
| Superiority or Other |
| Mean Difference (Net) | -1.272 | Standard Error of the Mean | 3.2390 | 2-Sided | 95 | -8.051 | 5.507 | Comparison of maximum heart rate Day 1. | Superiority or Other |
| Mean Difference (Net) | 0.988 | Standard Error of the Mean | 7.8616 | 2-Sided | 95 | -15.470 | 17.443 | Comparison of maximum heart rate Day 7. | Superiority or Other |
| Mean Difference (Net) | 2.734 | Standard Error of the Mean | 3.4410 | 2-Sided | 95 | -4.468 | 9.936 | Comparison of mean heart rate Day 1. | Superiority or Other |
| Mean Difference (Net) | 4.783 | Standard Error of the Mean | 2.9409 | 2-Sided | 95 | -1.372 | 10.938 | Comparison of mean heart rate Day 7. | Superiority or Other |
| Mean Difference (Net) | -1.074 | Standard Error of the Mean | 3.3103 | 2-Sided | 95 | -8.003 | 5.854 | Comparison of mean heart rate Day 1. | Superiority or Other |
| Mean Difference (Net) | 1.569 | Standard Error of the Mean | 2.8291 | 2-Sided | 95 | -4.353 | 7.490 | Comparison of mean heart rate Day 7. | Superiority or Other |
| Day 1, AM dose, 5 minutes |
|
|
| Day 1, AM dose, 15 minutes |
|
|
| Day 1, AM dose, 1 hour |
|
|
| Day 1, AM dose, 6 hour |
|
|
| Day 1, AM dose, 12 hour |
|
|
| Day 1, PM dose, 5 minutes |
|
|
| Day 1, PM dose, 30 minutes |
|
|
| Day 7, AM dose, pre-dose |
|
|
| Day 7, AM dose, 5 minutes |
|
|
| Day 7, AM dose, 15 minutes |
|
|
| Day 7, AM dose, 1 hour |
|
|
| Day 7, AM dose, 6 hour |
|
|
| Day 7, AM dose, 12 hour |
|
|
| Day 7, PM dose, 5 minutes |
|
|
| Day 7, PM dose, 30 minutes |
|
|
| Day 7, 0-12 hours |
|
| Day 7, 12-24 hours |
|
| Day 7 |
|
|
| Ratio |
| 1.060 |
| Standard Error of the Mean |
| 0.2057 |
| 2-Sided |
| 90 |
| 0.739 |
| 1.520 |
SE logs is presented as standard error of mean. Comparison of GSK233705 100 µg twice daily Day 7 versus Day 1. |
| Superiority or Other |
| PM Dose, Day 1 |
|
| PM Dose, Day 7 |
|
| Ratio |
| 1.190 |
| Standard Error of the Mean |
| 0.2482 |
| 2-Sided |
| 90 |
| 0.770 |
| 1.838 |
SE logs is presented as standard error of mean. Comparison of Cmax AM dose for GSK233705 100 µg twice daily Day 7 versus Day 1. |
| Superiority or Other |
| Ratio | 0.979 | Standard Error of the Mean | 0.2269 | 2-Sided | 90 | 0.658 | 1.457 | SE logs is presented as standard error of mean. Comparison of Cmax PM dose for GSK233705 50 µg twice daily Day 7 versus Day 1. | Superiority or Other |
| Ratio | 1.028 | Standard Error of the Mean | 0.2407 | 2-Sided | 90 | 0.674 | 1.568 | SE logs is presented as standard error of mean. Comparison of Cmax PM dose for GSK233705 100 µg twice daily Day 7 versus Day 1. | Superiority or Other |
| T-half, Day 7, AM dose |
|
|
| T-last, Day 1, AM dose |
|
|
| T-last, Day 7, AM dose |
|
|
| T-last, Day 1, PM dose |
|
|
| T-last, Day 7, PM dose |
|
|
| T-max, Day 1, AM dose |
|
|
| T-max, Day 7, AM dose |
|
|
| T-max, Day 1, PM dose |
|
|
| T-max, Day 7, PM dose |
|
|
| Ae, Day 1, PM dose |
|
| Ae, Day 7, PM dose |
|
| Ratio |
| 1.644 |
| Standard Error of the Mean |
| 0.138 |
| 2-Sided |
| 90 |
| 1.290 |
| 2.095 |
SE logs is presented as standard error of mean. Comparison of Ae AM dose for GSK233705 100 µg twice daily Day 7 versus Day 1. |
| Superiority or Other |
| Day 1, PM dose |
|
| Day 7, PM dose |
|
| Day 7 |
|
|