Last updated: 11/07/2018 04:19:55
A clinical trial to test a study drug in volunteers who develop asthma following exercise
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
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.
Trial 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
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
Timeframe: Baseline (pre dose) and 60 minutes following the exercise challenge at 24 hours post dose of each treatment period.
Secondary outcomes:
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
Timeframe: 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)
Timeframe: 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
Timeframe: 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
Timeframe: 0 to 90 minutes following exercise challenge of each treatment period
Assessment of vital signs: systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Timeframe: Pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge of treatment period
Assessment of vital signs: Heart rate (HR)
Timeframe: Pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge of each treatment period
Number of participants with abnormal electrocardiogram (ECG) findings
Timeframe: Pre dose, 2 hours, 9.5 hours and 24 hours prior to exercise challenge and 60 minutes following exercise challenge at 2 hours of each treatment period
Assessment of clinical chemistry parameters: Albumin, Total Protein
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment period
Assessment of clinical chemistry parameters: Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Gamma Glutamyl Transferase (GGT)
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment period
Assessment of clinical chemistry parameters: Direct Bilirubin, Total Bilirubin, Creatinine
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment period
Assessment of clinical chemistry parameters: Calcium, Chloride, Glucose, Potassium, Sodium, Urea/blood urea nitrogen (BUN)
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment period
Assessment of hematology parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils (TN) (ANC - Absolute Neutrophil Count), Platelet count, White Blood Cell count (WBC)
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment period
Assessment of hematology parameters: Hemoglobin, Mean Corpuscle Hemoglobin concentration (MCHC)
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment period
Assessment of hematology parameters: Hematocrit
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment period
Assessment of hematology parameters: Mean Corpuscle Hemoglobin (MCH)
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment period
Assessment of hematology parameters: Mean Corpuscle Volume (MCV)
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment period
Assessment of hematology parameters: Red Blood Cell count (RBC)
Timeframe: Pre dose and 25 hours and 30 minutes post dose of each treatment period
Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Timeframe: Up to follow up (7 to 21 days) following last dose
Percentage change from Baseline in blood Leukotriene B4 (LTB4)
Timeframe: Baseline (pre dose) up to 24 Hours post dose of each treatment period
Percentage change from Baseline in urine Leukotriene E4 (LTE4)
Timeframe: Baseline (pre dose) up to 24 Hours post dose of each treatment period
Derived pharmacokinetic (PK) parameters for GSK2190915
Timeframe: Pre dose, 2 hours, 3.5 hours, 9.5 hours, 11 hours and 24 hours following exercise challenge of each treatment period
Interventions:
Drug: Placebo
Drug: GSK2190915
Enrollment:
47
Observational study model:
Not applicable
Primary completion date:
2009-15-07
Time perspective:
Not applicable
Clinical publications:
Kent S, Pearlman D, Menendez R, Sterling R, Tarpay M, Miller D, Bentley J, Norris G.The effect of a 5-lipoxygenase activating protein (FLAP) inhibitor, GSK2190915, in patients with mild asthma who experience exercise induced bronchoconstriction..Allergy Asthma Proc.2014;35(2):126-133
Medical condition
Asthma
Product
fiboflapon
Collaborators
Not applicable
Study date(s)
December 2008 to July 2009
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 55 years
Accepts healthy volunteers
No
- 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.
- 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).
Inclusion and exclusion 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.
Trial location(s)
Location
GSK Investigational Site
Pittsburgh, Pennsylvania, United States, 15213
Status
Study Complete
Location
GSK Investigational Site
Oklahoma City, Oklahoma, United States, 73120
Status
Study Complete
Location
GSK Investigational Site
El Paso, Texas, United States, 79925
Status
Terminated/Withdrawn
Location
GSK Investigational Site
North Dartmouth, Massachusetts, United States, 02747
Status
Study Complete
Location
GSK Investigational Site
Orangeburg, South Carolina, United States, 29118
Status
Study Complete
Location
GSK Investigational Site
Denver, Colorado, United States, 80230
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2009-15-07
Actual study completion date
2009-15-07
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
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