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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Asthma

Treatments: Drug: GSK2190915; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00812929

112025

Details and patient eligibility

About

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.

Full description

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. Subjects will be invited to complete a screening visit, during which time exercise induced bronchoconstriction must be demonstrated, defined as a decrease between 20-40% in FEV1 compared to baseline immediately following exercise challenge. Eligible subjects will complete a randomized, double-blind, five-way crossover study. Subjects will be randomized to a single dose of either 10 mg, 50 mg, 100 mg, 200 mg GSK2190915, or placebo during each treatment period. Each treatment period will last 2 days and will include various assessments following exercise challenge at 2, 9.5, and 24 hours post dose. A minimum 7 day washout between treatment periods will be required. Regardless if a subject completes or prematurely withdraws from the study, a follow up visit will be completed 7-21 days following last dose.

Enrollment: 47 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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47 participants in 5 patient groups, including a placebo group

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo

GSK2190915 10 mg

Experimental group

Treatment:

Drug: GSK2190915

GSK2190915 50 mg

Experimental group

Treatment:

Drug: GSK2190915

GSK2190915 100 mg

Experimental group

Treatment:

Drug: GSK2190915

GSK2190915 200 mg

Experimental group

Treatment:

Drug: GSK2190915