Urine Concentrations of Vilanterol After Inhaled Administration of Vilanterol/Fluticasone Furoate

• Status: Completed
• Trial end date: 2020-12-14
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Bispebjerg Hospital
• Collaborator: Rigshospitalet, Denmark
• Treatments: Fluticasone; Xhance

Criteria

Inclusion Criteria:

• Healthy

• Age between 18 and 39 years, both included at time of screening

• Ability to correctly use the inhaler device

• Active at least 5 h pr. week (defined as endurance exercise)

• VO2-max classified as high or very high (table 1)(Astrand, 1960) measured during an incremental test to exhaustion at the screening visit

• Male or non-pregnant female

• Females of childbearing potential has to use one or more of the following highly effective methods for contraception in order to be included:

• Vasectomized partner

• Bilateral tubal occlusion

• Sexual abstinence

• Intrauterine device

• Hormonal contraception

• Females who are considered to have no childbearing potential are

• Bilateral tubal ligation

• Bilateral oophorectomy

• Complete hysterectomy

• Postmenopausal defined as 12 months with no menses without an alternative medical cause

• Non-smokers

• No daily use of prescribed medication

Exclusion Criteria:

• Diagnosis of heart, pulmonary (including asthma in Global initiative for asthma (GINA) 2-5), intestinal and renal diseases

• Allergy towards the active drug or any substances used in the drug

• Non-compliance with the protocol