Last updated: 11/04/2018 04:28:46

Effect of GSK1160724 In Healthy Volunteers

GSK study ID
AC5108696
See study documents
Clinicaltrials.gov ID
NCT00555022
EudraCT ID
2007-004835-45
EU CT Number
Not applicable
Trial status
Completed
Completed
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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
Trial description: GSK1160724 is a potent mAChR antagonist, which is being developed for
treatment of chronic obstructive pulmonary disease (COPD)
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Not applicable
Allocation:
Randomized
Primary outcomes:

Number of subjects with adverse events (AEs)

Timeframe: Up to Week 24

Number of subjects with abnormal values for blood pressure

Timeframe: Up to Week 24

Number of subjects with abnormal values for heart rate

Timeframe: Up to Week 24

Number of subjects with abnormal electrocardiogram (ECG) findings

Timeframe: Up to Week 24

Number of subjects with abnormal findings after holter monitoring

Timeframe: Up to 24 hour

Forced expiratory volume in 1 second (FEV1)

Timeframe: Up to Week 24

Forced vital capacity (FVC)

Timeframe: Up to Week 24

Number of subjects having abnormal hematology laboratory parameters

Timeframe: Up to Week 24

Number of subjects with abnormal clinical chemistry parameters

Timeframe: Up to Week 24

Number of subjects with abnormal values for urinalysis

Timeframe: Up to Week 24

Maximum value for resting heart rate over 0-4 hour

Timeframe: Up to 4 hours

Maximum value for resting blood pressure over 0-4 hour

Timeframe: Up to 4 hours

Maximum value for resting ECG over 0-4 hour

Timeframe: Up to 4 hours

Weighted mean of resting heart rate over 0-4 hour

Timeframe: Up to 4 hours

Weighted mean of resting blood pressure over 0-4 hour

Timeframe: Up to 4 hours

Weighted mean of resting ECG over 0-4 hour

Timeframe: Up to 4 hours

Secondary outcomes:

Plasma concentrations of GSK1160724

Timeframe: 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

Timeframe: 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

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

Urine concentrations of GSK1762245

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

Maximum observed concentration (Cmax) of GSK1160724

Timeframe: 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

Cmax of GSK1762245

Timeframe: 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

Time to Cmax (Tmax) of GSK1160724

Timeframe: 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

Tmax of GSK1762245

Timeframe: 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

Time to last observed plasma concentration (Tlast) of GSK1160724

Timeframe: 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

Tlast of GSK1762245

Timeframe: 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

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

Timeframe: 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

AUC (0-T) of GSK1762245

Timeframe: 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

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

Timeframe: 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

AUC (0-infinity) of GSK1762245

Timeframe: 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

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

Timeframe: 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

Lambda z of GSK1762245

Timeframe: 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

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

Timeframe: 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

T1/2 of GSK1762245

Timeframe: 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

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

Timeframe: Up to 24 hours

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

Timeframe: Up to 24 hours

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

Timeframe: Up to 24 hours

Serial sGaw measurements over 48 hours of GSK1160724 and tiotropium bromide

Timeframe: Up to 48 hours

Interventions:
Drug: GSK1160724
Drug: Tiotropium bromide
Drug: Placebo
Enrollment:
21
Observational study model:
Not applicable
Primary completion date:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Pulmonary Disease, Chronic Obstructive
Product
revefenacin
Collaborators
Not applicable
Study date(s)
December 2007 to April 2008
Type
Interventional
Phase
1

Participation criteria

Sex
Female & Male
Age
18 - 55 years
Accepts healthy volunteers
Yes
  • Healthy male and female subjects. Female subjects must be of non-child bearing potential.
  • Aged between 18-55 years inclusive
  • 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
Inclusion and exclusion 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

Trial location(s)

Location
Status
Contact us
Contact us
Location
GSK Investigational Site
Harrow, Middlesex, United Kingdom, HA1 3UJ
Status
Will Be Recruiting
Contact us

Study documents

Scientific result summary
Available language(s): English
Download document(s)

If you wish to request for full study report, please contact - [email protected]

Results overview

Refer to study documents

Recruitment status
Completed
Actual primary completion date
Not applicable
Actual study completion date
2008-07-04

Plain language summaries

Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

Additional information about the trial

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