Effect of GSK1160724 In Healthy Volunteers

NCT00555022 | Completed Phase 1

• 1 other identifier: AC5108696
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Pulmonary Disease, Chronic Obstructive

Keywords

Anticholinergic,; FTIH,; Muscarinic Receptor Antagonist,; Plethysmography; COPD,

Outcome Measures

Primary Outcomes (16)

• 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.

  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

Secondary Outcomes (22)

• 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 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

• Urine concentrations of GSK1160724

  0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours

• Urine concentrations of GSK1762245

  0-2 hours, 2-8 hours, 8-12 hours and 12-24 hours

• 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

Study Arms (1)

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

Drug: GSK1160724; Drug: Tiotropium bromide; Drug: Placebo

Interventions

GSK1160724 DRUG

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

All subjects

Tiotropium bromide DRUG

Tiotropium bromide capsules will be supplied with a dose of 18 micrograms administered via a HandiHaler device.

All subjects

Placebo DRUG

Subjects will receive placebo.

All subjects

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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 is unable to use the DISKUS™ and/or HandiHaler inhaler devices correctly at screening

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Harrow, Middlesex, HA1 3UJ, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 6, 2007
• First Posted: November 7, 2007
• Study Start: December 12, 2007
• Primary Completion: April 7, 2008
• Study Completion: April 7, 2008
• Last Updated: September 8, 2017

Record last verified: 2017-09

Locations

GB (1)