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GSK1160724 is a potent mAChR antagonist, which is being developed for treatment of chronic obstructive pulmonary disease (COPD)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All subjects | Experimental | Eligible subjects will receive one of the following treatment in cohort I and cohort II in five different treatment periods; Placebo, GSK1160724 (10 micrograms, 50 micrograms or 125 micrograms) and tiotropium bromide |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GSK1160724 | Drug | GSK1160724 will be available with dosing strengths of 10, 50 and 125 micrograms/blister for inhalation using the DISKUS inhaler. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects with adverse events (AEs) | An AE is any untoward medical occurrence in a clinical study subjects, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. | Up to Week 24 |
| Number of subjects with abnormal values for blood pressure | Systolic and diastolic blood pressure will be measured in a semi-recumbent position after 5 minutes rest. | Up to Week 24 |
| Number of subjects with abnormal values for heart rate | Heart rate will be measured in a semi-recumbent position after 5 minutes rest. | Up to Week 24 |
| Number of subjects with abnormal electrocardiogram (ECG) findings | Triplicate 12-lead ECGs will be measured in a semi-recumbent position after 5 minutes rest at each time point using ECG machine. | Up to Week 24 |
| Number of subjects with abnormal findings after holter monitoring | Holter monitoring will be conducted at 24 hour. | Up to 24 hour |
| Forced expiratory volume in 1 second (FEV1) | Lung function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. | Up to Week 24 |
| Forced vital capacity (FVC) | Lung function will be measured by FVC, defined as the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma concentrations of GSK1160724 | Plasma samples will be collected at the indicated time points to measure the concentration of GSK1160724. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Plasma concentrations of GSK1762245 |
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Inclusion Criteria:
Exclusion Criteria:
The subject has taken:
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Harrow | Middlesex | HA1 3UJ | United Kingdom |
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| Label | URL |
|---|---|
| Results for study AC5108696 can be found on the GSK Clinical Study Register. | View source |
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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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| ID | Term |
|---|---|
| D000069447 | Tiotropium Bromide |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
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| Tiotropium bromide | Drug | Tiotropium bromide capsules will be supplied with a dose of 18 micrograms administered via a HandiHaler device. |
|
| Placebo | Drug | Subjects will receive placebo. |
|
| Up to Week 24 |
| Number of subjects having abnormal hematology laboratory parameters | Hematology parameters will be assessed as a measure of safety. | Up to Week 24 |
| Number of subjects with abnormal clinical chemistry parameters | Clinical parameters will be assessed as a measure of safety. | Up to Week 24 |
| Number of subjects with abnormal values for urinalysis | Urinalysis will be performed as a measure of safety. | Up to Week 24 |
| Maximum value for resting heart rate over 0-4 hour | Maximum value for heart rate over 0-4 hour will be determined. | Up to 4 hours |
| Maximum value for resting blood pressure over 0-4 hour | Maximum value for resting systolic and diastolic blood pressure over 0-4 hour will be determined. | Up to 4 hours |
| Maximum value for resting ECG over 0-4 hour | Maximum value for resting ECG over 0-4 hour will be determined. | Up to 4 hours |
| Weighted mean of resting heart rate over 0-4 hour | Weighted mean for resting heart rate over 0-4 hour will be determined. | Up to 4 hours |
| Weighted mean of resting blood pressure over 0-4 hour | Weighted mean for resting systolic and diastolic blood pressure over 0-4 hour will be determined. | Up to 4 hours |
| Weighted mean of resting ECG over 0-4 hour | Weighted mean for resting resting ECG over 0-4 hour will be determined. | Up to 4 hours |
Plasma samples will be collected at the indicated time points to measure the concentration of the active metabolite GSK1762245. |
| Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Urine concentrations of GSK1160724 | Urine samples will be collected at the indicated time points to measure the concentration of GSK1160724. | 0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours |
| Urine concentrations of GSK1762245 | Urine samples will be collected at the indicated time points to measure the concentration of the active metabolite GSK1762245. | 0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours |
| Maximum observed concentration (Cmax) of GSK1160724 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Cmax of GSK1762245 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Time to Cmax (Tmax) of GSK1160724 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Tmax of GSK1762245 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Time to last observed plasma concentration (Tlast) of GSK1160724 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Tlast of GSK1762245 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Area under the plasma concentration time curve from time 0 to last time of quantifiable concentration (AUC [0-T]) of GSK1160724 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| AUC (0-T) of GSK1762245 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Area under the plasma concentration time curve from time 0 to infinity (AUC [0-infinity]) of GSK1160724 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| AUC (0-infinity) of GSK1762245 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| The terminal phase elimination rate constant (Lambda z) of GSK1160724 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Lambda z of GSK1762245 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| The Terminal phase half life (T1/2) of GSK1160724 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| T1/2 of GSK1762245 | Blood samples will be collected at the indicated time points for pharmacokinetic analysis. | Pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours.12 hours, 16 hours, 24 hours, 48 hours Post-dose |
| Serial specific airway conductance (sGaw) response over 24 hours post-dose of GSK1160724 and tiotropium bromide | The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints. | Up to 24 hours |
| FEV1 over 24 hours post-dose of GSK1160724 and tiotropium bromide | The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints. | Up to 24 hours |
| FVC over 24 hours post-dose of GSK1160724 and tiotropium bromide | The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints. | Up to 24 hours |
| Serial sGaw measurements over 48 hours of GSK1160724 and tiotropium bromide | The sGaw is a measure of the change in specific airway conductance. It will be assessed by whole body plethysmograph at the indicated timepoints. | Up to 48 hours |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009930 |
| Organic Chemicals |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |