Study to Evaluate GSK2190915 in Subjects With Mild Asthma

A Randomised, Double-blind, Placebo-controlled, 3-period Cross-over Study to Evaluate the Effect of Two Doses of GSK2190915 on the Allergen-induced Early Asthmatic Response in Subjects With Mild Asthma

This study will evaluate the safety and effect of repeat oral doses of GSK2190915 on lung function in mild asthmatics using a number of clinical and biological markers of efficacy.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: GSK2190915

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7EW
    • GSK Investigational Site
  • London, United Kingdom, W1G 8HU
    • GSK Investigational Site
  • Manchester, United Kingdom, M23 9QZ
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body mass index within the range 18.5-35.0 kilograms/metre2 (kg/m2)
• Female subjects must be of non childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophrectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL and estradiol < 40 pg/ml (<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
• Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until 5 terminal half-lives post-last dose.
• 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 >70% of predicted at screening.
• Subjects who are current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit and have a pack history of <= 10 pack years.

[number of pack years = (number of cigarettes per day/20) x number of years smoked]

• 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 house dust mite, grass pollen and cat hair) on skin prick testing at screening, or within 12 months of study start.
• Methacholine challenge PC20 < 8 mg/mL at screening or previous (in last 6 months) AMP, histamine or methacholine challenge that confirms the diagnosis of asthma
• Screening allergen challenge demonstrates that the subject experiences an early 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. Data obtained from screening for LPA111834 may be used for this criteria.
• Signed and dated written informed consent is obtained from the subject
• The subject is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions.

Exclusion Criteria:

• Past or present disease, which as judged by the investigator or medical monitor, may affect the outcome of this study. These diseases include, but are not limited to, cardiovascular disease, malignancy, gastrointestinal disease, hepatic disease, renal disease, haematological disease, neurological disease, endocrine disease or pulmonary disease
• 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 >150 mmHg 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
• Symptomatic with hay fever at screening or predicted to have symptomatic hay fever during the time of study
• Administration of oral or injectable steroids within 5 weeks of screening or intranasal and/or inhaled steroids within 4 weeks of the screening visit.
• Unable to abstain from other medications including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-histamines and anti-asthma, 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 14 days before screening until the follow-up visit.
• Unable to abstain from short acting beta agonists within 8 hours prior to an allergen challenge, dosing with study drug or any lung function assessment.
• 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%.
• The subject has participated in a study with a new molecular entity during the previous 3 months or has participated in 4 or more clinical studies in the previous 12 months prior to the first dosing day.
• History of being unable to tolerate or complete allergen challenge tests.
• Subject is undergoing allergen desensitisation therapy.
• There is a risk of non-compliance with study procedures.
• History of blood donation (500 mL) within 3 months of starting the clinical study.
• The subject regularly drinks more than 28 units of alcohol in a week if male, or 21 units per week if female. One unit of alcohol is defined as a medium (125 ml) glass of wine, half a pint (250 ml) of beer or one measure (25 ml) of spirits.
• The subject has a screening QTc value of >450msec, PR interval outside the range 120 to 220msec or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T-wave).
• The subject has tested positive for hepatitis C antibody or hepatitis B surface antigen.
• The subject has tested positive for HIV antibodies.
• The subject has a positive pre-study urine cotinine/ breath carbon monoxide test or urine drug or urine or breath alcohol screen. A minimum list of drugs that will be screened for include Amphetamines, Barbituates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 3 day repeat dose	Drug: GSK2190915; Investigational Product

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Early Asthmatic Response	0-2 hours after allergen challenge on Day 3 of each treatment period.

Secondary Outcome Measures

Outcome Measure	Time Frame
Lung function as measured by FEV1	Days 1 and 3
Assess safety and tolerability	Throughout study

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: December 1, 2008
• Primary Completion (ACTUAL): July 1, 2009
• Study Completion (ACTUAL): July 1, 2009

Study Registration Dates

• First Submitted: December 8, 2008
• First Submitted That Met QC Criteria: December 18, 2008
• First Posted (ESTIMATE): December 22, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): October 12, 2016
• Last Update Submitted That Met QC Criteria: October 11, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Asthma; Oral; Challenge; Dose; Allergen; GSK2190915; Repeat
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 112356

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. Dataset Specification
   Information identifier: 112356
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 112356
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: 112356
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 112356
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Annotated Case Report Form
   Information identifier: 112356
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 112356
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: 112356
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register