A Clinical Trial to Test a Study Drug in Volunteers Who Develop Asthma Following Exercise

NCT00812929 | Completed Phase 2 Results

• 1 other identifier: 112025
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 6

Brief Summary

This study is intended to determine the dose response and duration of action of GSK2190915 in mild asthmatic adult subjects who experience exercise-induced bronchoconstriction.

Conditions

Asthma

Keywords

Asthma, Exercise Induced Asthma, Exercise Induced Bronchospasm

Outcome Measures

Primary Outcomes (1)

• Maximal Percentage Change From Pre-exercise Baseline Forced Expiratory Volume in 1 Second (FEV1) to the Minimum FEV1 Collected Within 60 Minutes Following the Exercise Challenge at 24 Hours Post Dose

  FEV1 was recorded in triplicate, with participant encouraged to inhale fully despite any presence of chest tightness. For FEV1, a pre-challenge Baseline was defined for each challenge time point as maximum of triplicate measurements performed prior to challenge. The maximal percentage change within 60 minutes following exercise challenge was derived by taking minimum (i.e., most negative) percentage change in FEV1 over 5, 10, 15, 30, 45 and 60 minutes post challenge. Percent change FEV1 = 100\*(FEV1 - Pre-challenge FEV1)/ Pre-challenge FEV1. If the exercise challenge was not completed successfully (i.e. heart rate maintained at \>=80% of the predicted value for 6 minutes), FEV1 maximal percent change (0-60)was set to be missing. Analysis was performed using a mixed effects model, including period, treatment and covariates for predose FEV1. Estimates and 95% confidence intervals for treatment difference between each active dose and placebo for each challenge time point were calculated.

  Baseline (pre dose) and 60 minutes following the exercise challenge at 24 hours post dose of each treatment period.

Secondary Outcomes (21)

• Maximal Percentage Change From Pre-exercise Baseline FEV1 to the Minimum FEV1 Collected Within 60 Minutes Following the Exercise Challenge at 2 and 9.5 Hours Post Dose

  Baseline (pre dose) and 60 minutes following the exercise challenge at 2 and 9.5 hours post dose of each treatment period.

• Weighted Mean (WM) for FEV1 Percentage Change From Baseline Recorded During 0 to 60 Minutes Following Exercise Challenge (FEV1 WM0-60)

  Baseline (pre dose) and 0 to 60 minutes following exercise challenge at 2, 9.5 and 24 hours post dose of each treatment period.

• Time to FEV1 Recovery to Within 5 Percent of Baseline Following Exercise Challenge

  0 to 60 minutes following exercise challenge at 2, 9.5 and 24 hours post dose of each treatment period

• Number of Participants Using a Short Acting Beta-2 Agonist (Rescue Medication) During 0 to 90 Minutes Following Exercise Challenge

  0 to 90 minutes following exercise challenge of each treatment period

• Assessment of Vital Signs: Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge of treatment period

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

GSK2190915 10 mg

EXPERIMENTAL

Drug: GSK2190915

GSK2190915 50 mg

EXPERIMENTAL

Drug: GSK2190915

GSK2190915 100 mg

EXPERIMENTAL

Drug: GSK2190915

GSK2190915 200 mg

EXPERIMENTAL

Drug: GSK2190915

Interventions

Placebo DRUG

The current study will include a placebo arm to allow for a valid evaluation of adverse events attributable to GSK2190915 versus those independent of GSK2190915.

Placebo

GSK2190915 DRUG

This study will assess FEV1 at various intervals following exercise challenge in subjects who have been administered a single dose of 10 mg, 50 mg, 100 mg, or 200 mg GSK2190915, compared to a placebo control.

GSK2190915 10 mg; GSK2190915 100 mg; GSK2190915 200 mg; GSK2190915 50 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males and females aged 18 to 55 years inclusive.
• Female subjects must be of non childbearing potential including pre-menopausal females with documented hysterectomy or double oophorectomy or tubal ligation 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. Hormone replacement therapy (HRT) is permitted for post-menopausal females.
• Male subjects must agree to use one of the protocol outlined contraception methods. This criterion must be followed from the time of the first dose of study medication until 3 months after administration of last dose.
• Body weight greater than or equal to 50 kg and Body mass index within range of 18.5-35.0 kg/m2 inclusive.
• Pre-bronchodilator FEV1 \>70% of predicted at screening.
• Exercise induced bronchoconstriction, as defined as a 20-40% decrease in FEV1 compared to baseline immediately following exercise challenge at screening.
• Current non-smokers who have not used any tobacco products in the 6-month period preceding the screening visit with a pack history of less than or equal to 10 pack years \[number of pack years = (number of cigarettes per day/20) x number of years smoked\]
• Has provided signed and dated written informed consent
• Is able to understand and comply with the protocol requirements, instructions and protocol-stated restrictions.

You may not qualify if:

• Chronic use of inhaled corticosteroids (ICS) for the treatment of persistent asthma.
• Past or present disease, which as judged by the investigator or medical monitor, may affect the outcome of this study or the subject's safety. These diseases include, but are not limited to, cardiovascular disease, malignancy, hepatic disease, gastrointestinal disease, renal disease, haematological disease, neurological disease, endocrine disease or pulmonary disease (with the exception of asthma, but including chronic bronchitis, emphysema, bronchiectasis or pulmonary fibrosis).
• Treated for or diagnosed with clinical depression within six months of screening or has a history of significant psychiatric illness.
• Known history of hypertension or is hypertensive at screening which, in the opinion of the Investigator, deems the subject unfit to complete exercise challenge. Hypertension at screening is defined as persistent systolic BP \>150 mmHg or diastolic BP \> 90mmHg.
• Known history of gastrointestinal bleeding.
• Respiratory tract infection within 2 weeks prior to the first dose of study medication.
• Asthma exacerbations requiring treatment with oral corticosteroids: any exacerbations within 4 weeks of the screening visit or two or more exacerbations within 2 months of the screening visit or admittance to hospital for an asthma exacerbation within 6 months of the screening visit.
• 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.
• History of alcohol/drug abuse or dependence within 12 months of the study. Abuse of alcohol defined as an average weekly intake of \>14 drinks/week for men or \>7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• Use of prescription or non-prescription drugs (including CYP 3A4 inhibitors and inducers, vitamins and dietary or herbal supplements), from 14 days before screening until the follow-up visit, unless in the opinion of the Investigator and sponsor the medication will not interfere with the study. Inhaled beta-2 agonists and acetaminophen (up to 4 g per day) for the treatment of minor ailments, eg headache, are permitted. Hormone replacement therapy (HRT) is also permitted for post-menopausal females.
• Unable to washout the following protocol defined prohibited medications within the defined times:
• Following exercise challenge during the screening visit, the subject experiences a greater than 40% fall in FEV1 compared to baseline.
• Following exercise challenge during the screening visit, the subject is not able to recover to at least 20% of baseline FEV1 following administration of short acting beta-2 agonists.
• Requires rescue medication before all lung function assessments are completed following the exercise challenge at screening
• Symptomatic with hay fever at screening or predicted to have symptomatic hayfever during the time of exercise challenge which, in the opinion of the Investigator, would interfere with the outcome of the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (6)

GSK Investigational Site

Denver, Colorado, 80230, United States

Location

GSK Investigational Site

North Dartmouth, Massachusetts, 02747, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73120, United States

Location

GSK Investigational Site

Pittsburgh, Pennsylvania, 15213, United States

Location

GSK Investigational Site

Orangeburg, South Carolina, 29118, United States

Location

GSK Investigational Site

El Paso, Texas, 79925, United States

Location

Related Publications (1)

• Kent SE, Bentley JH, Miller D, Sterling R, Menendez R, Tarpay M, Pearlman DS, Norris V. The effect of GSK2190915, a 5-lipoxygenase-activating protein inhibitor, on exercise-induced bronchoconstriction. Allergy Asthma Proc. 2014 Mar-Apr;35(2):126-33. doi: 10.2500/aap.2014.35.3723.

  PMID: 24717789 DERIVED

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; Asthma, Exercise-Induced

Interventions

3-(3-tert-butylsulfanyl-1-(4-(6-ethoxypyridin-3-yl)benzyl)-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl)-2,2-dimethylpropionic acid

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Exercise-Induced Allergies

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: December 18, 2008
• First Posted: December 22, 2008
• Study Start: December 1, 2008
• Primary Completion: June 1, 2009
• Study Completion: July 15, 2009
• Last Updated: September 19, 2017
• Results First Posted: September 19, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will share

Locations

US (6)