A Clinical Trial to Test a Study Drug in Volunteers Who Develop Asthma Following Exercise
Condition: Asthma
MeSH terms: Asthma
Intervention: Placebo; GSK2190915
Intervention description: 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.; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Asthma, Exercise Induced Asthma, Exercise Induced Bronchospasm

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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.

        Exclusion Criteria:

          -  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:

        Medication Exclusion Period Oral or injectable corticosteroids - No use within 5 weeks of
        the screening visit Inhaled, Intranasal and topical steroids - No use within 4 weeks of the
        screening visit Long acting beta-2 agonists - No use within 48 hours of an exercise
        challenge or dosing or lung function testing Short acting beta-2 agonists - No use within 6
        hours of an exercise challenge or dosing or lung function testing

          -  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.

          -  Participation in a study with a new molecular entity during the previous 3 months or 5
             half-lives (whichever is longer), or participation in a study without a new molecular
             entity during the previous month or 5 half-lives (whichever is longer), prior to the
             first dose of study medication.

          -  Undergoing allergen desensitisation therapy.

          -  There is a risk of subject non-compliance with study procedures.

          -  History of blood donation (500 mL) within 2 months of starting the clinical study.

          -  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).

          -  Positive pregnancy test for females.

          -  Positive test for hepatitis C antibody or hepatitis B surface antigen.

          -  Positive test for HIV antibodies.

          -  Positive pre-study urine cotinine/ breath carbon monoxide test and or urine drug/urine
             alcohol screen. A minimum list of drugs that will be screened for include
             Amphetamines, Barbiturates, Cocaine, Opiates, Cannabinoids and Benzodiazepines.

          -  Has an affiliation with the Investigative Site. Participation of site personnel, or
             their spouses or children, is not allowed.