Clinical trial NCT00539825: Effect of GSK704838 In Healthy Volunteers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: Anticholinergic,
Plethysmography
Muscarinic Receptor Antagonist,
COPD,
FTIH,
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-10-05
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: 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 outcomes:
measure: - Plasma and urine concentrations of GSK704838 and derived pharmacokinetic parameters over 48h post-dose. - Serial sGaw, Raw and FEV1 measurements over 24h post-dose.
measure: 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.
measure: Serial sGaw measurements over 48 hours for the last period in each cohort dose of GSK704838 and tiotropium bromide.
Other outcomes:
Locations:
city: Harrow
country: United Kingdom
facility: GSK Investigational Site
state: Middlesex
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: