Effect of GSK704838 In Healthy Volunteers

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

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

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: GSK704838

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Middlesex
    • Harrow, Middlesex, United Kingdom, HA1 3UJ
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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.
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.
Serial sGaw measurements over 48 hours for the last period in each cohort dose of GSK704838 and tiotropium bromide.

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (ACTUAL): February 1, 2008
• Study Completion (ACTUAL): February 1, 2008

Study Registration Dates

• First Submitted: October 4, 2007
• First Submitted That Met QC Criteria: October 4, 2007
• First Posted (ESTIMATE): October 5, 2007

Study Record Updates

• Last Update Posted (ESTIMATE): October 31, 2016
• Last Update Submitted That Met QC Criteria: October 28, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: COPD,; Plethysmography; FTIH,; Anticholinergic,; Muscarinic Receptor Antagonist,
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: AC6108697

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Annotated Case Report Form
   Information identifier: AC6108697
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: AC6108697
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Dataset Specification
   Information identifier: AC6108697
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: AC6108697
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: AC6108697
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: AC6108697
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: AC6108697
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register