Effect of GSK1160724 In Healthy Volunteers

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Randomized Double-blind, Placebo-controlled, Crossover, Dose Escalation Study to Examine the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK1160724 and Tiotropium Bromide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00555022
• Other study ID #: AC5108696
• Status: Completed
• Phase: Phase 1
• First received: November 6, 2007
• Last updated: September 5, 2017
• Start date: December 12, 2007
• Est. completion date: April 7, 2008

Study information

• Verified date: September 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

GSK1160724 is a potent mAChR antagonist, which is being developed for treatment of chronic obstructive pulmonary disease (COPD)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: April 7, 2008
• Est. primary completion date: April 7, 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• GSK1160724
GSK1160724 will be available with dosing strengths of 10, 50 and 125 micrograms/blister for inhalation using the DISKUS inhaler.
• Tiotropium bromide
Tiotropium bromide capsules will be supplied with a dose of 18 micrograms administered via a HandiHaler device.
• Placebo
Subjects will receive placebo.

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Harrow	Middlesex

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Number of subjects with abnormal findings after holter monitoring	Holter monitoring will be conducted at 24 hour.	Up to 24 hour
Primary	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
Primary	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.	Up to Week 24
Primary	Number of subjects having abnormal hematology laboratory parameters	Hematology parameters will be assessed as a measure of safety.	Up to Week 24
Primary	Number of subjects with abnormal clinical chemistry parameters	Clinical parameters will be assessed as a measure of safety.	Up to Week 24
Primary	Number of subjects with abnormal values for urinalysis	Urinalysis will be performed as a measure of safety.	Up to Week 24
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Secondary	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
Secondary	Plasma concentrations of GSK1762245	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Results for study AC5108696 can be found on the GSK Clinical Study Register.