Fluticasone Propionate/Formoterol fumarate/Glycopyrrolate

Batefenterol (BAT) is a novel bifunctional molecule that combines muscarinic antagonism and beta2-agonism in a single molecule and is in development for the treatment of chronic obstructive pulmonary disease (COPD). FF is a corticosteroid approved as the inhaled corticosteroid (ICS) component of a combination product, with vilanterol (VI), a long-acting beta2-agonist for COPD. In the current study FF will be investigated as an inhaled product in combination with BAT, for treatment of COPD.
This study is an open-label, six-way crossover, single and repeat dose study to evaluate the systemic pharmacokinetics, safety and tolerability of FF and BAT when administered via the ELLIPTA™ alone, in combination, or concurrently at 3 times the clinical dose, following a single dose, and at the proposed clinical dose, following repeat doses.
This study will consist of screening period, 6 treatment periods, and a follow-up visit. Each subject will have 3 periods in which they receive a single dose treatment regimen (3 inhalations on Day 1 of each single dose study period) and 3 periods in which they receive a single dose treatment regimen followed by a 7-day, once-daily, repeated dose. On Day 1 of those periods, subjects will receive their single dose as 3 inhalations. On Days 2-8, subjects will receive 1 inhalation per day for the repeated dose regimen. There will be a minimum of 7-day washout between each treatment periods. All subjects will receive 9 treatments and follow-up procedures will be done 7 14 days after the last dose.
Forty eight healthy subjects will be enrolled into the study, such that approximately 40 subjects complete dosing and PK assessments. The total duration of participation for each subject in this study will be up to 15 weeks. ELLIPTA is a registered trademark of the GlaxoSmithKline [GSK] group of companies.

Inhaled corticosteroids (ICS) have a number of known class effects including hypothalamic-pituitary-adrenocortical (HPA) axis suppression. Although the safety of inhaled Fluticasone Furoate (FF) on the HPA axis of adults and adolescent asthmatic patients has been established, it is important to assess the risk of suppression in children so as to establish whether this medicine can be safely used in this young population. This study aims to evaluate the effect of inhaled FF on the HPA axis of children 5-11 years of age (inclusive) with persistent asthma compared with placebo. Approximately 143 subjects will be enrolled. Subjects will enter a 7 to 14 day run-in period on oral montelukast 4 milligrams (mg) (5 year old subjects) or 5 mg (6-11 year old subjects) once daily. Eligible subjects will be randomized to receive once-daily FF inhalation powder 50 micrograms (mcg) or once-daily placebo inhalation powder in the morning via the ELLIPTA™ inhaler for 42 days. Subjects will continue to receive open label montelukast during the treatment period. All subjects will be provided albuterol/salbutamol inhalation aerosol, to use as needed to treat acute asthma symptoms throughout the study.
ELLIPTA is a registered trademark of the GlaxoSmithKline group of companies.