A Study to Assess the Safety and Pharmacokinetics of Inhaled Doses of GSK233705 and GW642444 in Healthy Subjects.

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00671216
First received: April 30, 2008
Last updated: October 14, 2010
Last verified: October 2010
  Purpose

GW642444 and GSK233705 are in development for treatment of Chronic Obstructive Pulmonary Disease. Development of these two inhaled drugs as a combination therapy would have potential for improved patient benefit as they both work through different mechanisms and the combined bronchodilatory effect might be additive. This study will look at the this combination, for the first time, in healthy subjects.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease (COPD)
Drug: GSK233705
Drug: GW642444
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Single Centre, Randomised, Placebo-controlled, Four-way Cross Over Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK233705 and GW642444 as Monotherapies and in Combination in Healthy Subjects.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • General safety endpoints: measured over 24 hours post dose for all 4 dose periods, heart rate, systolic and diastolic blood pressure, 12- lead ECG and lung function and clinical laboratory safety tests. Adverse events over whole study.

Secondary Outcome Measures:
  • Blood levels of GW642444, Blood levels of GSK233705, Blood Levels of potassium

Estimated Enrollment: 16
Study Start Date: May 2008
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: GSK233705 Drug: GW642444
    Other Names:
    • GSK233705
    • GW642444
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring.
  • Male or female between 18 and 65 years of age.
  • Female subjects must be of non childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy or postmenopausal
  • Male subjects must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until 90 days post-last dose.
  • BMI within the range 18 - 30 kg/m2 (inclusive).
  • Average QTc(B)≤450 msec taken from triplicate assessments at screening.
  • No clinically active and relevant abnormality on 12-lead ECG at screening or 24h Holter ECG.
  • Normal spirometry (FEV1 ≥ 80% of predicted, FEV1/FVC ≥ 70%).
  • Non-smokers (never smoked or not smoking for >6 months with <10 pack years history (Pack years = (cigarettes per day smoked/20) x number of years smoked))
  • 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

Exclusion Criteria:

  • Any clinically important abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or ECG (12-lead). 24hr Holter monitoring outside normal limits.
  • A history of breathing problems (i.e. history of asthmatic symptomatology, unless asthma in childhood that has now resolved and no longer requires maintenance therapy which should not be an exclusion).
  • A mean QTc(B) value at screening >450msec, or an ECG that is not suitable for QT measurements (e.g. LBBB or poorly defined termination of the T wave).
  • 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 at screening.
  • The subject has a positive pre-study drug/alcohol screen. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
  • A positive test for HIV antibody (if determined by the local SOP's).
  • History of high alcohol consumption within 3months of the study defined as:
  • an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units (males), or defined as an average weekly intake of greater than 14 units or an average daily intake of greater than 2 units (females). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Use of prescription or non-prescription drugs, (except for simple analgesics eg paracetamol), including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or nicotine-containing products prior to screening.
  • The subject is unable to use the novel dry powder inhaler correctly.
  • The subject has a known allergy or hypersensitivity to ipratropium bromide, Tiotropium, atropine and any of its derivatives.
  • Any adverse reaction including immediate or delayed hypersensitivity to any β2 agonist or sympathomimetic drug,
  • The subject has a known allergy or hypersensitivity to milk protein or the excipients lactose monohydrate and MgSt.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00671216

Locations
United Kingdom
GSK Investigational Site
London, United Kingdom, NW10 7NS
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials, MD GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00671216     History of Changes
Other Study ID Numbers: DB1111509
Study First Received: April 30, 2008
Last Updated: October 14, 2010
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by GlaxoSmithKline:
Muscarinic Receptor Antagonist
Anticholinergic
ß2 agonist
healthy subjects
safety
tolerability
pharmacokinetics
pharmacodynamics
GSK233705
GS642444

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on October 22, 2014