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

NCT00857857 | Completed Phase 2 Results

• 1 other identifier: 110762
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Asthma

Keywords

asthma; late phase response; allergen; challenge; GW870086X

Outcome Measures

Primary Outcomes (1)

• Late Asthmatic Response (LAR): Minimum FEV1 Between 4-10 Hours After Allergen Challenge on Day 13 of Each Treatment Period

  Analyzed using a mixed effects model including covariates for participant level Baseline FEV1 and period level Baseline FEV1. Participant level Baseline defined as the mean of Day 1 pre-dose values across periods for each participant and period level Baseline as the difference between the Day 1 pre-dose value and participant level Baseline for each period. Absolute change from saline Baseline was calculated for each participant and time point as value equal to highest challenge value minus highest saline value. Minimum FEV1 over 4-10 hours post allergen challenge was minimum value of all the post-saline time points between 4 to 10 hours (4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5 and 10 hours). The adjusted mean is presented as least square mean (LSM).

  4-10 hours after allergen challenge on Day 13 of each treatment period

Secondary Outcomes (26)

• LAR: Weighted Mean FEV1 Between 4-10 Hours After Allergen Challenge on Day 13 of Each Treatment Period.

  4-10 hours after allergen challenge on Day 13 of each treatment period

• EAR: Minimum FEV1 and Weighted Mean FEV1 Between 0-2 Hours After Allergen Challenge on Day 13 of Each Treatment Period.

  0-2 hours after challenge on Day 13 of each treatment period (approximately 17 weeks)

• Concentration of Exhaled NO Pre-dose on Day 13 of Each Treatment Period

  Day 13 of each treatment period (approximately 17 weeks)

• Concentration of Exhaled NO Post-dose on Day 13 of Each Treatment Period

  Day 13 of each treatment period (approximately 17 weeks)

• Number of Participants With Adverse Events (AE), Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE)

  Up to 17 weeks

Study Arms (1)

13 day repeat dose

EXPERIMENTAL

Drug: GW870086X; Drug: FP; Drug: Placebo

Interventions

GW870086X DRUG

Investigational product

13 day repeat dose

FP DRUG

Positive control

13 day repeat dose

Placebo DRUG

Placebo control

13 day repeat dose

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Wiesbaden, Hesse, 65187, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

GSK Investigational Site

Berlin, 14050, Germany

Location

Related Publications (1)

• Bareille P, Allen A, Hardes K, Donald A. Effect of repeat inhaled doses of GW870086 on the allergen-induced early and late asthmatic response in subjects with mild asthma. Curr Drug Ther. 2013;8(2)

  BACKGROUND

Related 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.

MeSH Terms

Conditions

Asthma

Interventions

GW870086X

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2009
• First Posted: March 9, 2009
• Study Start: February 16, 2009
• Primary Completion: November 3, 2009
• Study Completion: November 3, 2009
• Last Updated: February 20, 2018
• Results First Posted: February 20, 2018

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

DE (4)