Effect of GSK1160724 In Healthy Volunteers
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Interventions
- Registration Number
- NCT00555022
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
GSK1160724 is a potent mAChR antagonist, which is being developed for treatment of chronic obstructive pulmonary disease (COPD)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
- Healthy male and female subjects. Female subjects must be of non-child bearing potential.
- Aged between 18-55 years inclusive
- Non-smokers
- Normal spirometry
- A signed and dated written informed consent is obtained from the subject
- The subject is capable of giving informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- Available to complete the study
- The subject is greater than or equal to 50kg with a body mass index within the range 19.0 to 29.9 kg/m2 inclusive
- Response to ipratropium bromide
- Any clinically relevant and important abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or ECG (12-lead or Holter)
- A history of breathing problems
- A mean QTc(B) value > 450ms, the QTc(B) of the 3 screening ECGs are not within 10% of the mean, a PR interval outside the range 90-210ms or an ECG that is not suitable for QT measurements at screening
- A history of elevated resting blood pressure or a mean blood pressure higher than 140/90 mmHg at screening
- A mean heart rate outside the range 40-90 bpm inclusive at screening
- History of use of tobacco- or nicotine-containing products within 6 months of screening, and/or positive urine cotinine test results at screening
- Where participation in the study would result in donation of blood in excess of 500mL within a 56 day period at screening
- The subject is currently taking regular (or a course of) medication, whether prescribed or not, including herbal remedies such as St John's Wort etc.
The subject has taken:
- prescription medications for 14 days prior to first dose of study drug, or
- Over-the-counter (OTC) medications/preparations (including herbal remedies, etc.) excluding simple analgesics for 48 hours prior to first dose of study drug,unless it is judged by the Investigator not to compromise the subject's safety or influence the outcome of the study.
- The subject has participated in a study with a new molecular entity or any other trial within a period of 3 months prior first dose of study drug
- The subject has tested positive for hepatitis C antibody (third generation enzyme immunoassay), hepatitis B surface antigen or HIV antibodies (if tested according to site SOP's) at screening.
- The subject has tested positive for drugs-of-abuse at screening
- The subject has tested positive for urine alcohol (including ethanol) at screening The detection of alcohol would not be an exclusion at screening but would need to be negative pre-dose and during the study
- The subject is unable to use the DISKUS™ and/or HandiHaler inhaler devices correctly at screening
- The subject has a suspected history of alcohol abuse within the six months previous to the screening visit
- The subject has a known allergy or hypersensitivity to magnesium stearate, milk protein or the excipient lactose monohydrate, iodine, ipratropium bromide, tiotropium bromide, atropine and/or any of its derivatives
- The subject has a significant clinical history of prostatic hypertrophy or narrow angle glaucoma
- The subject has received an allogeneic bone marrow transplant
- The subject has claustrophobia that may be aggravated by entering the whole body plethysmography cabinet
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description All subjects Tiotropium bromide 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 All subjects GSK1160724 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 All subjects Placebo 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
- Primary Outcome Measures
Name Time Method Number of subjects with adverse events (AEs) Up to Week 24 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.
Forced vital capacity (FVC) Up to Week 24 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.
Number of subjects with abnormal values for urinalysis Up to Week 24 Urinalysis will be performed as a measure of safety.
Number of subjects with abnormal values for blood pressure Up to Week 24 Systolic and diastolic blood pressure will be measured in a semi-recumbent position after 5 minutes rest.
Number of subjects with abnormal electrocardiogram (ECG) findings Up to Week 24 Triplicate 12-lead ECGs will be measured in a semi-recumbent position after 5 minutes rest at each time point using ECG machine.
Number of subjects with abnormal findings after holter monitoring Up to 24 hour Holter monitoring will be conducted at 24 hour.
Maximum value for resting ECG over 0-4 hour Up to 4 hours Maximum value for resting ECG over 0-4 hour will be determined.
Forced expiratory volume in 1 second (FEV1) Up to Week 24 Lung function will be measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second.
Number of subjects with abnormal clinical chemistry parameters Up to Week 24 Clinical parameters will be assessed as a measure of safety.
Maximum value for resting heart rate over 0-4 hour Up to 4 hours Maximum value for heart rate over 0-4 hour will be determined.
Number of subjects with abnormal values for heart rate Up to Week 24 Heart rate will be measured in a semi-recumbent position after 5 minutes rest.
Weighted mean of resting blood pressure over 0-4 hour Up to 4 hours Weighted mean for resting systolic and diastolic blood pressure over 0-4 hour will be determined.
Number of subjects having abnormal hematology laboratory parameters Up to Week 24 Hematology parameters will be assessed as a measure of safety.
Maximum value for resting blood pressure over 0-4 hour Up to 4 hours Maximum value for resting systolic and diastolic blood pressure over 0-4 hour will be determined.
Weighted mean of resting heart rate over 0-4 hour Up to 4 hours Weighted mean for resting heart rate over 0-4 hour will be determined.
Weighted mean of resting ECG over 0-4 hour Up to 4 hours Weighted mean for resting resting ECG over 0-4 hour will be determined.
- Secondary Outcome Measures
Name Time Method Plasma concentrations of 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 Plasma samples will be collected at the indicated time points to measure the concentration of the active metabolite GSK1762245.
Plasma concentrations 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 samples will be collected at the indicated time points to measure the concentration of GSK1160724.
Urine concentrations of GSK1160724 0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours Urine samples will be collected at the indicated time points to measure the concentration of GSK1160724.
Maximum observed concentration (Cmax) 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Time to Cmax (Tmax) 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Lambda z of 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Cmax of 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Tmax of 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Time to last observed plasma concentration (Tlast) 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Urine concentrations of GSK1762245 0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours Urine samples will be collected at the indicated time points to measure the concentration of the active metabolite GSK1762245.
Area under the plasma concentration time curve from time 0 to last time of quantifiable concentration (AUC [0-T]) 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Tlast of 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
AUC (0-T) of 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Area under the plasma concentration time curve from time 0 to infinity (AUC [0-infinity]) 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
The terminal phase elimination rate constant (Lambda z) 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
The Terminal phase half life (T1/2) 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
FVC over 24 hours post-dose of GSK1160724 and tiotropium bromide Up to 24 hours The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
AUC (0-infinity) of 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
T1/2 of 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 Blood samples will be collected at the indicated time points for pharmacokinetic analysis.
Serial specific airway conductance (sGaw) response over 24 hours post-dose of GSK1160724 and tiotropium bromide Up to 24 hours The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
FEV1 over 24 hours post-dose of GSK1160724 and tiotropium bromide Up to 24 hours The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.
Serial sGaw measurements over 48 hours of GSK1160724 and tiotropium bromide Up to 48 hours The sGaw is a measure of the change in specific airway conductance. It will be assessed by whole body plethysmograph at the indicated timepoints.
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Harrow, Middlesex, United Kingdom