Urine Concentrations of Vilanterol After Inhaled Administration of Vilanterol/Fluticasone Furoate
Status:
Completed
Trial end date:
2020-12-14
Target enrollment:
Participant gender:
Summary
Introduction: The prevalence of asthma and exercise-induced bronchoconstriction is high in
the athletic population. In endurance sport, the prevalence has been reported to be as high
as 30-50% compared to the general population prevalence of approximately 5-10% in Western
countries. First-line treatment in asthma is reliever medication and inhaled corticosteroids
(ICS). Therefore, β2-adrenoceptor agonists and ICS are commonly prescribed drugs to athletes.
Although long-acting β2-agonists (LABA) are the most commonly used β2-agonists in asthma
management, development of ultra-long acting β2-agonists (U-LABA) as vilanterol may change
this. U-LABA has a long duration of action (24 hours) compared with LABA (12 hours). The
accumulated number of inhalations per day for elite athletes may thus be reduced when
prescribed with U-LABA as compared to LABA. Use of β2-agonists are restricted by the World
Anti-Doping Agency (WADA). As of 2018, β2-agonists salbutamol, formoterol and salmeterol are
allowed by inhalation in therapeutic doses, whereas other β2-agonists, such as terbutaline
and vilanterol still require the athlete to obtain a therapeutic use exemption (TUE). To
discriminate therapeutic use from supra-therapeutic misuse, WADA has established urinary
thresholds and decision limits based on urine concentrations of salbutamol, salmeterol and
formoterol. However, while data on urine concentrations of these three β2-agonists are
well-described in studies that simulate sport-specific situations that are applicable for
doping control, no such data exist for the novel U-LABA vilanterol. For instance, asthmatic
athletes using β2-agonists usually inhale the drug before training or competition as
prophylaxis for bronchoconstriction. Thus, studies are needed to investigate the urine
concentrations of vilanterol after inhaled administration in set-ups that are applicable to
doping control which this study aims to investigate.
Method: The study is divided in two phases. The first phase consists of a pharmacokinetic
pilot trial (EXP1). Depending on the analytical outcome of the pilot study, the study
proceeds into the second phase, which is a larger pharmacokinetic trial (EXP2). Both EXP1 and
EXP 2 are open label studies.
EXP1: 6 healthy, well trained individuals are recruited to perform two trial days. First
trial day consists of inhalation of the study drug in 4 times therapeutic dose followed by an
exercise session. Before second trial day subjects inhales 4 times the therapeutic dose at
home and on day 7 perform a training session. Urine and blood are collected in the following
72 hours both days.
EXP2: 20 healthy, well trained individuals are recruited to perform four trial days in the
same way as EXP1. But here both normal use and four times normal dose is investigated.