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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00812929
First received: December 18, 2008
Last updated: February 5, 2010
Last verified: February 2010
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Placebo
Drug: GSK2190915
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multi-centre, Randomized, Double-blind, Five-way Crossover Study Evaluating the Dose Response and Duration of Action of GSK2190915 Compared to Placebo in Subjects With Mild Asthma Who Experience Exercise Induced Bronchoconstriction.

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Maximal percentage change from pre-exercise baseline FEV1 to the minimum FEV1 at 24 hours post dose. [ Time Frame: 60 minutes following the exercise challenge. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Weighted Mean (WM) for FEV1 percentage change from baseline recorded. [ Time Frame: 0 to 60 minutes following exercise challenge (FEV1 WM0-60) ] [ Designated as safety issue: No ]
  • Time to FEV1 recovery to within 5% of baseline following exercise challenge. [ Time Frame: 90 minutes following exercise challenge ] [ Designated as safety issue: No ]
  • Proportion of subjects using a short acting beta-2 agonist (rescue medication). [ Time Frame: 0 to 90 minutes following exercise challenge. ] [ Designated as safety issue: No ]
  • Safety assessments: vital signs, ECG, safety laboratory parameters, adverse events. [ Time Frame: Study Duration ] [ Designated as safety issue: No ]
  • Leukotriene biomarkers LTB4 and LTE4 in blood and urine samples, respectively. [ Time Frame: 24 hours post dose ] [ Designated as safety issue: No ]
  • Derived PK parameters for GSK2190915. [ Time Frame: 24 hours post dose ] [ Designated as safety issue: No ]
  • Maximal percentage change from pre-exercise baseline FEV1 to the minimum FEV1 at 2 and 9.5 hours post dose. [ Time Frame: 60 minutes following the exercise challenge. ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: December 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK2190915 200 mg Drug: 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.
Experimental: GSK2190915 10 mg Drug: 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.
Placebo Comparator: Placebo Drug: Placebo
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.
Experimental: GSK2190915 100 mg Drug: 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.
Experimental: GSK2190915 50 mg Drug: 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.

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00812929

Locations
United States, Colorado
GSK Investigational Site
Denver, Colorado, United States, 80230
United States, Massachusetts
GSK Investigational Site
North Dartmouth, Massachusetts, United States, 02747
United States, Oklahoma
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73120
United States, Pennsylvania
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
GSK Investigational Site
Orangeburg, South Carolina, United States, 29118
United States, Texas
GSK Investigational Site
El Paso, Texas, United States, 79925
United States, Wisconsin
GSK Investigational Site
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Study Director, GSK
ClinicalTrials.gov Identifier: NCT00812929     History of Changes
Other Study ID Numbers: 112025
Study First Received: December 18, 2008
Last Updated: February 5, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Asthma, Exercise Induced Asthma, Exercise Induced Bronchospasm

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases

ClinicalTrials.gov processed this record on September 22, 2014