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OpenTrials
Completed

NCT Number: NCT00555022

Effect of GSK1160724 In Healthy Volunteers

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

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Key information

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

GSK Investigational Site

Harrow, Middlesex, HA1 3UJ, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

GSK1160724

Drug

GSK1160724 will be available with dosing strengths of 10, 50 and 125 micrograms/blister for inhalation using the DISKUS inhaler.

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.

Primary outcomes

  1. Number of subjects with adverse events (AEs)

    Time frame: 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.

  2. Number of subjects with abnormal values for blood pressure

    Time frame: Up to Week 24

    Systolic and diastolic blood pressure will be measured in a semi-recumbent position after 5 minutes rest.

  3. Number of subjects with abnormal values for heart rate

    Time frame: Up to Week 24

    Heart rate will be measured in a semi-recumbent position after 5 minutes rest.

  4. Number of subjects with abnormal electrocardiogram (ECG) findings

    Time frame: 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.

  5. Number of subjects with abnormal findings after holter monitoring

    Time frame: Up to 24 hour

    Holter monitoring will be conducted at 24 hour.

  6. Forced expiratory volume in 1 second (FEV1)

    Time frame: 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.

  7. Forced vital capacity (FVC)

    Time frame: 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.

  8. Number of subjects having abnormal hematology laboratory parameters

    Time frame: Up to Week 24

    Hematology parameters will be assessed as a measure of safety.

  9. Number of subjects with abnormal clinical chemistry parameters

    Time frame: Up to Week 24

    Clinical parameters will be assessed as a measure of safety.

  10. Number of subjects with abnormal values for urinalysis

    Time frame: Up to Week 24

    Urinalysis will be performed as a measure of safety.

  11. Maximum value for resting heart rate over 0-4 hour

    Time frame: Up to 4 hours

    Maximum value for heart rate over 0-4 hour will be determined.

  12. Maximum value for resting blood pressure over 0-4 hour

    Time frame: Up to 4 hours

    Maximum value for resting systolic and diastolic blood pressure over 0-4 hour will be determined.

  13. Maximum value for resting ECG over 0-4 hour

    Time frame: Up to 4 hours

    Maximum value for resting ECG over 0-4 hour will be determined.

  14. Weighted mean of resting heart rate over 0-4 hour

    Time frame: Up to 4 hours

    Weighted mean for resting heart rate over 0-4 hour will be determined.

  15. Weighted mean of resting blood pressure over 0-4 hour

    Time frame: Up to 4 hours

    Weighted mean for resting systolic and diastolic blood pressure over 0-4 hour will be determined.

  16. Weighted mean of resting ECG over 0-4 hour

    Time frame: Up to 4 hours

    Weighted mean for resting resting ECG over 0-4 hour will be determined.

Secondary outcomes

  1. Plasma concentrations of GSK1160724

    Time frame: 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.

  2. Plasma concentrations of GSK1762245

    Time frame: 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.

  3. Urine concentrations of GSK1160724

    Time frame: 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.

  4. Urine concentrations of GSK1762245

    Time frame: 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.

  5. Maximum observed concentration (Cmax) of GSK1160724

    Time frame: 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.

  6. Cmax of GSK1762245

    Time frame: 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.

  7. Time to Cmax (Tmax) of GSK1160724

    Time frame: 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.

  8. Tmax of GSK1762245

    Time frame: 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.

  9. Time to last observed plasma concentration (Tlast) of GSK1160724

    Time frame: 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.

  10. Tlast of GSK1762245

    Time frame: 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.

  11. Area under the plasma concentration time curve from time 0 to last time of quantifiable concentration (AUC [0-T]) of GSK1160724

    Time frame: 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.

  12. AUC (0-T) of GSK1762245

    Time frame: 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.

  13. Area under the plasma concentration time curve from time 0 to infinity (AUC [0-infinity]) of GSK1160724

    Time frame: 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.

  14. AUC (0-infinity) of GSK1762245

    Time frame: 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.

  15. The terminal phase elimination rate constant (Lambda z) of GSK1160724

    Time frame: 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.

  16. Lambda z of GSK1762245

    Time frame: 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.

  17. The Terminal phase half life (T1/2) of GSK1160724

    Time frame: 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.

  18. T1/2 of GSK1762245

    Time frame: 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.

  19. Serial specific airway conductance (sGaw) response over 24 hours post-dose of GSK1160724 and tiotropium bromide

    Time frame: Up to 24 hours

    The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.

  20. FEV1 over 24 hours post-dose of GSK1160724 and tiotropium bromide

    Time frame: Up to 24 hours

    The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.

  21. FVC over 24 hours post-dose of GSK1160724 and tiotropium bromide

    Time frame: Up to 24 hours

    The sGaw response will be assessed by whole body plethysmograph at the indicated timepoints.

  22. Serial sGaw measurements over 48 hours of GSK1160724 and tiotropium bromide

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study 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

Important dates

Study start
2007
Primary completion
2008
Study completion
2008
First posted
Nov 7, 2007
Registry last updated
Sep 8, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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