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A Study to Evaluate the Effect of GW870086X on Allergen Challenge in Mild Asthmatics

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00857857
First received: March 5, 2009
Last updated: March 22, 2012
Last verified: March 2012
  Purpose

The study will measure the early and late asthamtic response using an allergen challenge. This study will evaluate the safety and patients tolerance to repeat inhaled doses of GW870086X using a number of clinical and biological markers.


Condition Intervention Phase
Asthma
Mild Asthma
Drug: GW870086X
Drug: FP
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Placebo-controlled, Incomplete Block, Three-way Cross-over Study to Evaluate the Effect of Treatment With Repeat Inhaled Doses of GW870086X on the Allergen-induced Early and Late Asthmatic Response in Subjects With Mild Asthma

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Late asthmatic response [ Time Frame: 4-10 hours after allergen challenge on Day 13 of each treatment period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Early asthmatic response [ Time Frame: 0-2 hours after allergen challenge on Day 13 of each treatment period ] [ Designated as safety issue: No ]
  • Lung function as measured by FEV1 [ Time Frame: Days 1 and 13 ] [ Designated as safety issue: No ]
  • Assess safety and tolerability [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Exhaled NO [ Time Frame: Days 1 and 13 ] [ Designated as safety issue: No ]
  • Effect on bronchial hyperactivity as measured by methacholine challenge [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
  • Assessment of established markers of anti-inflammatory activity in sputum [ Time Frame: Day 14 ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: February 2009
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 13 day repeat dose Drug: GW870086X
Investigational product
Drug: FP
Positive control
Drug: Placebo
Placebo control

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male subjects between 18 and 65 years of age inclusive.
  • Male subjects must agree to use one of the contraception methods listed in Section 8. This criterion must be followed from the time of the first dose of study medication until 90-95 hours post-last dose.
  • BMI within the range 19.0 - 29.0 kg/m2 (inclusive).
  • Liver function tests (bilirubin, AST, ALT) within normal laboratory parameters at screening.
  • Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with intermittent short-acting beta -agonist therapy by inhalation.
  • Pre-bronchodilator FEV1 >65% of predicted at screening.
  • No history of smoking within 6 months of the start of the study, and with a total pack year history of <= 10 pack years
  • Demonstration of a positive wheal and flare reaction (>= 3 mm relative to negative control) to at least one allergen from a battery of allergens (including but not limited to house dust mite, grass pollen, cat dander, hazel, horse and birch) on skin prick testing at screening, or within 12 months of study start.
  • Screening allergen challenge demonstrates that the subject experiences both an early and late asthmatic response. The early asthmatic response must include a fall in FEV1 of >= 20% from the post saline value, on at least one occasion, between 5 and 30 minutes after the final concentration of allergen. The late asthmatic response must include a fall in FEV1 of >= 15% from the post saline value, on at least three occasions, two of which must be consecutive, between 4 and 10 hours after the final concentration of allergen.
  • Reproducible allergen challenge at screening (confirmation of the dose ascending allergen challenge by a bolus allergen challenge at least 14 days later).
  • Sensitivity to methacholine with a provocative concentration of methacholine resulting in a 20% fall in FEV1 (PC20 methacholine) of <8 mg/mL at screening.
  • Subjects who are able to produce acceptable induced sputum samples (as defined in the Study Procedures Manual).
  • Be able to give written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
  • Single QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block.

Exclusion Criteria:

  • Past or present disease, which as judged by the investigator, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease or pulmonary disease (including but not confined to chronic bronchitis, emphysema, bronchiectasis or pulmonary fibrosis).
  • Clinically significant abnormalities in safety laboratory analysis at screening.
  • Subject has known history of hypertension or is hypertensive at screening. Hypertension at screening is defined as persistent systolic BP >140mmHg or diastolic BP > 90mmHg.
  • Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the first dose of study medication.
  • History of life-threatening asthma, defined as an asthma episode that required intubation and/or was associated with hypercapnoea, respiratory arrest and/or hypoxic seizures.
  • Administration of oral, injectable or dermal steroids within 4 weeks or intranasal and/or inhaled steroids within 2 week of the screening visit.
  • The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
  • 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.
  • History of regular alcohol consumption within 6 months 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). 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, 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. Paracetamol is an exception and will be permitted at daily doses of up to 4 g from screening to follow-up.
  • Has taken Xanthines (including theophylline, but not including caffeine), anticholinergics, cromoglycates and/or long-acting beta-agonists within 1 week prior to screening and is unable to abstain from them throughout the study.
  • Unable to abstain from other medications including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines and anti-asthma (not including steroids), anti-rhinitis or hay fever medication, other than short acting inhaled beta-agonists and paracetamol (up to 4 g per day) for the treatment of minor ailments eg headache from 7 days before screening until the follow-up visit.
  • Unable to abstain from medication or supplements that significantly inhibit the cytochrome P450 subfamily enzyme CYP3A4, including ritonavir and ketoconazol from screening and throughout the study.
  • Unable to use the DISKHALER and/or DISKUS device correctly.
  • History of being unable to tolerate or complete methacholine or allergen challenge tests.
  • If, after 2 concurrent administrations of saline during the allergen challenge at screening the subjects still have a fall in FEV1 of greater than 10%.
  • Subject is undergoing allergen desensitisation therapy.
  • History of sensitivity to any of the study medications (including lactose), 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.
  • Subjects who are kept due to regulatory or juridical order in an institution.
  • Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months prior to screening.
  • Consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication.
  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: NCT00857857

Locations
Germany
GSK Investigational Site
Wiesbaden, Hessen, Germany, 65187
GSK Investigational Site
Hannover, Niedersachsen, Germany, 30625
GSK Investigational Site
Grosshansdorf, Schleswig-Holstein, Germany, 22927
GSK Investigational Site
Berlin, Germany, 14050
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00857857     History of Changes
Other Study ID Numbers: 110762
Study First Received: March 5, 2009
Last Updated: March 22, 2012
Health Authority: Germany: Bundesinstitut für Arzneimittel und Medizinprodukte

Keywords provided by GlaxoSmithKline:
asthma
late phase response
allergen
challenge
GW870086X

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on November 25, 2014