Effect of GSK704838 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 GSK704838 and Tiotropium Bromide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00539825
• Other study ID #: AC6108697
• Status: Completed
• Phase: Phase 1
• First received: October 4, 2007
• Last updated: October 28, 2016
• Start date: September 2007
• Est. completion date: February 2008

Study information

• Verified date: October 2016
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: National Research Ethics Service (NRES)
• Study type: Interventional

Clinical Trial Summary

GSK704838C is a potent, pan-active mAChR antagonist, which is being developed for once-daily treatment of chronic obstructive pulmonary disease (COPD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy male subject

• 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 =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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• GSK704838

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	adverse events, vital signs,12-lead ECG, Holter and ECG monitoring,lung function and clinical lab tests. These will be taken pre-dose and at multiple time points up to 48h at each treatment period.
Secondary	- Plasma and urine concentrations of GSK704838 and derived pharmacokinetic parameters over 48h post-dose. - Serial sGaw, Raw and FEV1 measurements over 24h post-dose.
Secondary	Serial specific airway conductance (sGaw), Forced Expiratory Volume in 1 second (FEV1) and Forced Vital Capacity measurements (FVC) over 24 hours post-dose of GSK704838 and tiotropium bromide.
Secondary	Serial sGaw measurements over 48 hours for the last period in each cohort dose of GSK704838 and tiotropium bromide.

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.