Last updated: 11/04/2018 08:23:31

Study To Evaluate GSK256066 In Subjects With Mild Bronchial Asthma

GSK study ID
IPA101985
See study documents
Clinicaltrials.gov ID
NCT00380354
See results summary
EudraCT ID
2005-005339-83
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

Official title: A two-centre, randomised, double-blind, placebo-controlled, 2-period cross-over study to evaluate the effect of treatment with repeat doses of inhaled GSK256066 on the allergen-induced late asthmatic response in subjects with mild asthma
Trial description: This study will evaluate the efficacy and safety of GSK256066 in the treatment of subjects with mild bronchial asthma, using a number of clinical and biological markers of efficacy.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Not applicable
Allocation:
Randomized
Primary outcomes:

Late Asthmatic Response (LAR): Absolute change from baseline in minimum Forced expiratory volume in 1 second (FEV1) between 4-10 hours after allergen challenge on Day 7 of each treatment period

Timeframe: Baseline (Day 1) and Day 7 of each treatment period

Secondary outcomes:

LAR: Absolute change from baseline weighted mean FEV1 between 4-10 hours after allergen challenge on Day 7 of each treatment period

Timeframe: Baseline (Day 1) and Day 7 of each treatment period

Provocative concentration of methacholine resulting in a 20 percent (%) reduction in FEV1 (PC20) on Day 8 of each treatment period

Timeframe: Day 8 of each treatment period

Early Asthmatic Response (EAR): Absolute change from baseline in minimum FEV1 and weighted mean FEV1 between 0-2 hours after allergen challenge on Day 7 of each treatment period

Timeframe: Baseline (Day 1) and Day 7 of each treatment period

Concentration of exhaled nitric oxide (NO) pre-dose on Day 1 and 7, post-dose on Day 7

Timeframe: Pre-dose on Days 1 and 7, post-dose on Day 7 and post-methacholine challenge on Day 8 of each treatment period

Absolute change from Baseline in Assessment of FEV1 pre-dose on Day 1 and 7 and post-dose on Day 7 (prior to allergen challenge)

Timeframe: Pre-dose on Day 1 (Baseline) and Pre-dose and post-dose on Day 7 (prior to allergen challenge) of each treatment period

Number of participants with treatment emergent adverse events (AEs)

Timeframe: 10-14 days after the last study dose in each period

Change From Baseline Supine Vital Signs Data- Systolic blood pressure (SBP) and Diastolic blood pressure (DBP)

Timeframe: Baseline (pre-dose Day 1) and Day 1 (post-dose 30 minute, 1, 2 hours) and Day 7 (post-dose 30 minute, 1, 2, 8, 24 hours) of each treatment period

Change From Baseline in Vital Signs Data- Heart rate

Timeframe: Baseline (pre-dose Day 1) and Day 1 (post-dose 30 minute, 1, 2 hours) and Day 7 (post-dose 30 minute, 1, 2, 8, 24 hours) of each treatment period

Change from Baseline Supine electrocardiogram (ECG) Data

Timeframe: Baseline (pre-dose Day 1) and Day 1 (post-dose 30 minute, 1, 2 hours), Day 4 (1 hour) and Day 7 (post-dose 30 minute, 1, 2, 8, 24 hours) of each treatment period

Change from Baseline Non-Challenge FEV1

Timeframe: Baseline (pre-dose Day 1) and at pre-dose, 1 hour on Day 7

Change from Baseline in Clinical Chemistry Data- Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase, Lactate Dehydrogenase

Timeframe: Baseline (pre-dose Day 1) and Day 4 pre-dose (only Creatine Kinase) and Day 7 pre-dose

Change from Baseline in Clinical Chemistry Data- Albumin, Total Protein

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Change from Baseline Clinical Chemistry Data- Total Bilirubin, Creatinine

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Change from Baseline in Clinical Chemistry Data- Calcium, Chloride, Glucose, Bicarbonate, Potassium, Sodium, Phosphorus Inorganic, Urea

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Change from Baseline in Clinical Chemistry Data- C-Reactive protein

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Change from Baseline Clinical Chemistry Data- Creatinine Clearance

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Change from Baseline in Clinical Chemistry Data- Troponin I

Timeframe: Baseline (pre-dose Day 1) and Day 4 pre-dose and Day 7 pre-dose

Change from Baseline in Haematology Data- Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet count, White Blood Cell Count

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Change from Baseline in Hematology Data- Fibrinogen, Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC)

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Change from Baseline in Hematology Data- Hematocrit

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Change from Baseline in Hematology Data- Mean Corpuscle Hemoglobin

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Change from Baseline Hematology Data- Mean Corpuscle Volume

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Change from Baseline in Hematology Data- Red Blood Cell Count

Timeframe: Baseline (pre-dose Day 1) and Day 7 pre-dose

Markers of inflammation in sputum- Bronchocytes, Eosinophils, Lymphocytes, Macrophages and Neutrophils

Timeframe: 2 hours Day 4 and 1 hour Day 8 in each period

Markers of inflammation in sputum- Total Leukocyte Count

Timeframe: 2 hours Day 4 and 1 hour Day 8 in each period

Markers of inflammation in sputum- Cytokines

Timeframe: 2 hours Day 4 and 1 hour Day 8 in each period

Markers of inflammation in blood

Timeframe: Pre-dose Day 1 and Day 7, 2 hours Day 4 and Day 7 in each period

Markers of Phosphodiesterase-4 (PDE4) activity in blood and sputum

Timeframe: Day 4 (2 hour) and Day 8 (1 hour) in each period

Summary of pharmacokinetic parameter (PK) area under the plasma concentration-time curve from time zero to last measurable concentration- AUC(0-t) for GSK256006 and metabolite GSK614917

Timeframe: Pre-dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 10, 11, 12, 24 hour post- dose on Day 1 and Day 7 in each period

Summary of pharmacokinetic parameter maximum observed plasma concentration (Cmax) for GSK256006 and metabolite GSK614917

Timeframe: Pre-dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 10, 11, 12, 24 hour post- dose on Day 1 and Day 7 in each period

Summary of pharmacokinetic parameter time of maximum observed concentration (tmax) for GSK256006 and metabolite GSK614917

Timeframe: Pre-dose, 10 minutes, 30 minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 10, 11, 12, 24 hour post- dose on Day 1 and Day 7 in each period

Summary of pharmacokinetic parameter Assessing Accumulation Ratio- AUC(0-t) for GSK256006

Timeframe: Pre-dose, 10 minutes, 30minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 10, 11, 12, 24 hour post- dose on Day 1 and Day 7 in each period

Summary of pharmacokinetic parameter Parameters Assessing Accumulation Ratio- Cmax for GSK256006

Timeframe: Pre-dose, 10 minutes, 30minutes, 45 minutes, 1, 2, 3, 4, 6, 8, 10, 11, 12, 24 hour post-dose on Day 1 and Day 7 in each period

Interventions:
  • Drug: GSK256066
    • Enrollment:
    24
    Primary completion date:
    2007-20-06
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Asthma
    Product
    GSK256066
    Collaborators
    Not applicable
    Study date(s)
    September 2006 to June 2007
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    18+ years
    Accepts healthy volunteers
    No
    • Inclusion criteria
    • Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with intermittent short-acting beta -agonist therapy by inhalation.
    Inclusion and exclusion criteria
    Inclusion criteria:
    • Inclusion criteria
    • Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with intermittent short-acting beta -agonist therapy by inhalation.
    • Pre-bronchodilator FEV1 >75% of predicted at screening.
    • Non-smoker
    • Demonstration of a positive reaction to at least one allergen from a battery of allergens (including house dust mite, grass pollen and cat hair on skin prick testing at screening, or within 12 months of study start.
    • Have Asthmatic response
    • Able and willing to give written informed consent to take part in the study.
    • Available to complete all study measurements. Exclusion criteria:
    • History of cardiovascular disease
    • Clinically significant abnormalities in safety laboratory analysis at screening including any subject who has greater than “trace urine protein levels” following urinalysis at screening.
    • History of hayfever
    • The subject has tested positive for hepatitis C antibody or hepatitis B surface antigen.
    • The subject has tested positive for HIV antibodies.
    • The subject has positive drugs of abuse test.
    • Subjects weighing less than 50kg are to be excluded from participating in the study.
    • The subject has participated in a study with a new molecular entity during the previous 3 months.
    • History of being unable to tolerate or complete methacholine, and/or allergen challenge tests.
    • There is a risk of non-compliance with study medication or study procedures.
    • History of blood donation (450 mL) within 2 months of starting the clinical study.
    • The subject regularly drinks more than 28 units of alcohol in a week if male, or 21 units per week if female. One unit of alcohol is defined as a medium (125 ml) glass of wine, half a pint (250 ml) of beer or one measure (24 ml) of spirits.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    London, United Kingdom, SE1 9RT
    Status
    Will Be Recruiting
    Contact us
    Location
    GSK Investigational Site
    Manchester, Lancashire, United Kingdom, M23 9LT
    Status
    Will Be Recruiting
    Contact us

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2007-20-06
    Actual study completion date
    2007-20-06

    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.

    Additional information about the trial

    Additional information
    Not applicable
    Participate in clinical trial
    Access to clinical trial data by researchers
    Visit website