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Effect of GSK1160724 In Healthy Volunteers

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00555022
First Posted: November 7, 2007
Last Update Posted: September 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
GSK1160724 is a potent mAChR antagonist, which is being developed for treatment of chronic obstructive pulmonary disease (COPD)

Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive Drug: GSK1160724 Drug: Tiotropium bromide Drug: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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.

  • 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.

  • 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.

  • 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.

  • Number of subjects with abnormal findings after holter monitoring [ Time Frame: Up to 24 hour ]
    Holter monitoring will be conducted at 24 hour.

  • 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.

  • 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.

  • Number of subjects having abnormal hematology laboratory parameters [ Time Frame: Up to Week 24 ]
    Hematology parameters will be assessed as a measure of safety.

  • Number of subjects with abnormal clinical chemistry parameters [ Time Frame: Up to Week 24 ]
    Clinical parameters will be assessed as a measure of safety.

  • Number of subjects with abnormal values for urinalysis [ Time Frame: Up to Week 24 ]
    Urinalysis will be performed as a measure of safety.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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 Outcome Measures:
  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.


Enrollment: 21
Actual Study Start Date: December 12, 2007
Study Completion Date: April 7, 2008
Primary Completion Date: April 7, 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All subjects
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
Drug: GSK1160724
GSK1160724 will be available with dosing strengths of 10, 50 and 125 micrograms/blister for inhalation using the DISKUS inhaler.
Drug: Tiotropium bromide
Tiotropium bromide capsules will be supplied with a dose of 18 micrograms administered via a HandiHaler device.
Drug: Placebo
Subjects will receive placebo.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00555022


Locations
United Kingdom
GSK Investigational Site
Harrow, Middlesex, United Kingdom, HA1 3UJ
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00555022     History of Changes
Other Study ID Numbers: AC5108696
First Submitted: November 6, 2007
First Posted: November 7, 2007
Last Update Posted: September 8, 2017
Last Verified: September 2017

Keywords provided by GlaxoSmithKline:
Anticholinergic,
FTIH,
Muscarinic Receptor Antagonist,
Plethysmography
COPD,

Additional relevant MeSH terms:
Lung Diseases
Chronic Disease
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Disease Attributes
Pathologic Processes
Lung Diseases, Obstructive
Tiotropium Bromide
Bromides
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Parasympatholytics
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Anticonvulsants