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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00671216
First Posted: May 5, 2008
Last Update Posted: October 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  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
Pulmonary Disease, Chronic Obstructive Drug: GSK233705 Drug: GW642444 Drug: GSK233705 and GW642444 Drug: Placebo Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
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. [ Time Frame: Up to Day 2 ]

Secondary Outcome Measures:
  • Blood levels of GW642444, Blood levels of GSK233705, Blood Levels of potassium [ Time Frame: Pre-dose; Day 1- 5, 15 and 30 minutes, 1, 2, 4, 5,6, 8, 12, 16 and 24 hours and Day 2 ]

Enrollment: 16
Actual Study Start Date: May 20, 2008
Study Completion Date: July 7, 2008
Primary Completion Date: July 7, 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Period 1
Subjects will receive first placebo, then GSK233705, GW642444 and combination of GSK233705 and GW642444
Drug: GSK233705
Subjects will receive 200 (mcg) microgram once daily as a single dose
Drug: GW642444
Subjects will receive 50 mcg once daily as a single dose
Other Name: GSK233705
Drug: GSK233705 and GW642444
Subjects will receive combination of GSK233705 200 mcg and GW642444 50 mcg as a single oral dose
Drug: Placebo
Placebo matching study medication will be inhaled by subjects
Experimental: Period 2
Subjects will receive first combination of GSK233705 and GW642444, then placebo, GSK233705 and GW642444
Drug: GSK233705
Subjects will receive 200 (mcg) microgram once daily as a single dose
Drug: GW642444
Subjects will receive 50 mcg once daily as a single dose
Other Name: GSK233705
Drug: GSK233705 and GW642444
Subjects will receive combination of GSK233705 200 mcg and GW642444 50 mcg as a single oral dose
Drug: Placebo
Placebo matching study medication will be inhaled by subjects
Experimental: Period 3
Subjects will receive first GSK233705, then GW642444, combination of GSK233705 and GW642444 and later placebo
Drug: GSK233705
Subjects will receive 200 (mcg) microgram once daily as a single dose
Drug: GW642444
Subjects will receive 50 mcg once daily as a single dose
Other Name: GSK233705
Drug: GSK233705 and GW642444
Subjects will receive combination of GSK233705 200 mcg and GW642444 50 mcg as a single oral dose
Drug: Placebo
Placebo matching study medication will be inhaled by subjects
Experimental: Period 4
Subjects will receive first GW642444, then combination of GSK233705 and GW642444, placebo, and later GSK233705
Drug: GSK233705
Subjects will receive 200 (mcg) microgram once daily as a single dose
Drug: GW642444
Subjects will receive 50 mcg once daily as a single dose
Other Name: GSK233705
Drug: GSK233705 and GW642444
Subjects will receive combination of GSK233705 200 mcg and GW642444 50 mcg as a single oral dose
Drug: Placebo
Placebo matching study medication will be inhaled by subjects

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00671216


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

Additional Information:
Publications:
GSK has concluded that it is not feasible to publish this study in a peer-reviewed scientific journal because the nature of the study is unlikely to be of interest to a journal. GSK is providing the attached study results summary.

Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: DB1111509
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: DB1111509
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: DB1111509
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: DB1111509
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: DB1111509
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: DB1111509
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: DB1111509
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00671216     History of Changes
Other Study ID Numbers: DB1111509
First Submitted: April 30, 2008
First Posted: May 5, 2008
Last Update Posted: October 4, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
URL: http://

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

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