Last updated: 11/07/2018 10:25:54
A 3-period crossover study with GSK573719 as monotherapy in adult subjects with asthma
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official title: A multi-national, randomized, double-blind, placebo-controlled, 3-period crossover study with GSK 573719 as monotherapy in adult subjects with asthma
Trial description: This is a multi-national, randomized, double-blind, 3-period crossover, incomplete block design to evaluate 5 once-daily and 2 twice-daily doses of GSK573719 in combination with placebo. The study will explore the dose range of GSK573719 in asthmatic subjects who are currently using non-ICS controller medications. Subjects will participate in the study for up to a maximum of 14 weeks. At randomization subjects will be stratified by age to ensure adequate exposure to GSK573719 throughout the expected age range. The primary endpoint will be trough FEV1 obtained 24 hours after the last morning dose on Day 14 of each treatment sequence. A sub-group of subjects at selected sites (approximately 30% of the total population) will have additional serial assessments for spirometry, ECG and Holter, and pharmacokinetic sampling at the start and end of each treatment period. Safety assessments will include monitoring for adverse events, laboratory tests, asthma symptom assessments and twice daily PEF evaluation. Consenting subjects will have a blood sample taken for pharmacogenetic analysis.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Final dose-response model for trough forced expiratory volume in one second (FEV1)
Timeframe: Day 15 of each treatment period (up to Study Day 71)
Change from Baseline in Trough FEV1 on Day 15 of each treatment period
Timeframe: Day 15 of each treatment period (up to Study Day 71)
Number of participants with any adverse event (AE) or serious adverse event (SAE)
Timeframe: From Baseline until the end of Treatment Period 3 (up to Study Day 70)
Number of participants with asthma exacerbations during the Treatment Period
Timeframe: From Baseline until the end of Treatment Period 3 (up to Study Day 70)
Change from Baseline in systolic blood pressure on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Change from Baseline in diastolic blood pressure on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Change from Baseline in pulse rate on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Change from Baseline in albumin, total protein, and hemoglobin on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70))
Change from Baseline in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase (CK), gamma glutamyl transferase (GGT) and lactate dehydrogenase (LDH) on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Change from Baseline in direct bilirubin, indirect bilirubin, total bilirubin, and creatinine on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Change from Baseline in calcium, chloride, carbon dioxide, glucose, potassium, sodium, and urea/blood urea nitrogen (BUN) on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Change from Baseline in basophils, eosinophils, lymphocytes, monocytes, total neutrophils (ANC - Absolute neutrophil count), platelet, and leukocytes count on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Change from Baseline in the percentage of basophils, eosinophils, lymphocytes, monocytes, and segmented neutrophils in blood on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Change from Baseline in hematocrit on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Number of participants for the indicated urinalysis parameters tested by dipstick on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70))
Urine pH on Day 14 of each treatment period
Timeframe: Day 14 of each treatment period (up to Study Day 70)
Urine specific gravity on Day 14 of each treatment period
Timeframe: Day 14 of each treatment period (up to Study Day 70)
Number of participants with the indicated abnormal electrocardiogram findings
Timeframe: Day 14 of each treatment period (up to Study Day 70)
Number of participants with the indicated 24 hour Holter findings
Timeframe: Day 14 of each treatment period (up to Study Day 70)
Secondary outcomes:
Change from Baseline (BL) in the weighted mean (WM) 0-24 hour FEV1 obtained post-AM dose on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Change in Baseline in serial FEV1 over 0-24 hours after the morning dose on Day 14 of each treatment period
Timeframe: Baseline and Day 14 of each treatment period (up to Study Day 70)
Change from Baseline in mean morning (AM) and evening (PM) pre-treatment Peak Expiratory Flow (PEF) over Day 7 to Day 14 of each treatment period
Timeframe: Baseline (Day 7 prior to each treatment period) and the last 7 days of each treatment period (up to Study Day 70)
Change from Baseline in the mean number of puffs per day of rescue albuterol/salbutamol over Day 7 to Day 14 of each treatment period
Timeframe: Baseline (Day 7 prior to each treatment period) and the last 7 days of each treatment period (up to Study Day 70)
Interventions:
Drug: GSK573719 Active treatment or Placebo
Procedure/surgery: GSK573719 (Sub-group cohort)
Drug: Salbutamol/Albuterol
Enrollment:
350
Observational study model:
Not applicable
Primary completion date:
2013-05-02
Time perspective:
Not applicable
Clinical publications:
Shuying Yang, Navin Goyal , Misba Beerahee , Roopa Trivedi , Laurie Lee , Steven Pascoe. Dose–response modelling of umeclidinium and fluticasone furoate/umeclidinium in asthma. Eur J Clin Pharmacol.2015;71(9):1051-1058.
Medical condition
Asthma
Product
umeclidinium bromide
Collaborators
Not applicable
Study date(s)
May 2012 to February 2013
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Written informed consent
- Outpatient (sub-group will have 3 overnight stays at clinic)
- History of life threatening asthma
- Severe asthma exacerbation
Inclusion and exclusion criteria
Inclusion criteria:
- Written informed consent
- Outpatient (sub-group will have 3 overnight stays at clinic)
- Diagnosis of asthma (NIH 2007) for at least 6 months
- Male or Eligible female (females of child-bearing potential must use acceptable method of birth control)
- A best AM pre-bronchodilator FEV1 of 60% to 85% of predicted normal value at Screening
- Reversibility of disease demonstrated by at least 12% and 200mL increase in FEV1 .
- Subjects must have been prescribed a non-corticosteroid controller at least 3 months preceding Visit 1, and/or a short-acting beta 2 agonist, without the use of inhaled corticosteroids in the 4 weeks prior to Visit 1
- Subjects must be able to replace their current short-acting Beta-2-agonist with albuterol/salbutamol aerosol inhaler for the duration of the study
- Subjects must be judged capable of withholding albuterol/salbutamol for at least 4 hours prior to study visits
Exclusion criteria:
- History of life threatening asthma
- Severe asthma exacerbation
- Respiratory infection within expected to affect subject's ability to participate
- Concurrent respiratory disease
- Current smoker or smoking history of 10 pack years or more
- Diseases preventing use of anticholinergics
- Other clinically significant, uncontrolled condition or disease which would pose a safety risk to the patient, or confound interpretation of study results
- Drug allergy to any Beta-2-agonist, sympathomimetic drug, intranasal, inhaled or systemic corticosteroid therapy
- Known or suspected sensitivity to the constituents of the Novel DPI (ie lactose)
- History of severe milk protein allergy
- Administration of prescription or over-the-counter medication that would significantly affect the course of asthma, or interact with the study drug
- Any infirmity, disability or disease of a child or family member likely to impair compliance
- Alcohol or substance abuse history
- Viral hepatitis B surface antigen or Hepatitis C antibody
- Known HIV-positive history.
- Affiliation with investigator or site staff
Trial location(s)
Location
GSK Investigational Site
Columbia, Missouri, United States, 65203
Status
Study Complete
Location
GSK Investigational Site
San Antonio, Texas, United States, 78229
Status
Study Complete
Location
GSK Investigational Site
Santiago de Surco, Lima, Peru, Lima 33
Status
Study Complete
Location
GSK Investigational Site
Bellevue, Nebraska, United States, 68123-4303
Status
Study Complete
Location
GSK Investigational Site
Spartanburg, South Carolina, United States, 29303
Status
Study Complete
Location
GSK Investigational Site
Weinheim, Baden-Wuerttemberg, Germany, 69469
Status
Study Complete
Location
GSK Investigational Site
Sunset, Louisiana, United States, 70584
Status
Study Complete
Location
GSK Investigational Site
Orangeburg, South Carolina, United States, 29118
Status
Study Complete
Location
GSK Investigational Site
Geesthacht, Schleswig-Holstein, Germany, 21502
Status
Study Complete
Location
GSK Investigational Site
Bethesda, Maryland, United States, 20814
Status
Study Complete
Location
GSK Investigational Site
Newport Beach, California, United States, 92663
Status
Study Complete
Location
GSK Investigational Site
St. Louis, Missouri, United States, 63141
Status
Study Complete
Study documents
Clinical study report
Available language(s): English
Scientific result summary
Available language(s): English
Protocol
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
2013-05-02
Actual study completion date
2013-05-02
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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