SUMMARY

Inhalationsspray innehåller drivgas för att skapa det tryck som behövs för att skapa en aerosol. De drivgaser som nu finns på marknaden måste fasas ut då de bidrar till växthuseffekten. Bytet till en mer klimatneutral drivgas förutsätter dock att varken effekt eller säkerhet försämras.

Why checkups matter

Metered-dose inhalers (MDI) contain propellants to pressurize the inhaler so that the drug formulation is delivered as an aerosol. The use of propellants is safe for the users, but being greenhouse gases, contribute to a higher carbon footprint. As not all patients can be switched to other inhaler types, MDIs with alternative propellants are under development. These propellants must have considerably lower global warming potential, without compromising pharmacokinetic properties.

Hence, three en core posters were presented to share the development of a replacement for the currently used propellant . These studies aimed at answering these questions:

• Is the novel formulation bioequivalent to the MDI on the market?
• Can relative lung bioavailability and total systemic exposure in healthy volunteers be demonstrated?
• Is the broncho constriction potential and safety profile in line with the current MDI?

Bioequivalence

Comparing a triple fixed dose BDP/FF/GB* in high dose with current and novel propellant, respectively, in healthy volunteers, bioequivalence was fully demonstrated for beclomethasone (measured as active metabolite B17MP) and formoterol. For glycopyrronium, the 90% CI were marginally above the bioequivalence upper limit, which was not considered clinically relevant.

Bioavailability

Comparing a triple fixed dose BDP/FF/GB in medium dose with current and novel propellant, respectively, in healthy volunteers, bioequivalence was fully demonstrated for beclomethasone (measured as active metabolite B17MP), formoterol and glycopyrronium. For pulmonary availability, bioequivalence was demonstrated for formoterol. For beclomethasone and glycopyrronium, the 90%CIs were marginally outside the bioequivalence limits which was considered not clinically relevant.

Bronchoconstriction potential

In the third study, comparing sprays with no active principle, no propellant-induced bronchoconstriction event was observed, and the safety profile was equivalent between the two propellants in patients with mild asthma. Taste sensation was included as exploratory objective, but no taste difference between the 2 propellants was reported.

Conclusion

Safety and tolerability of both propellants were similar in all three studies. The outcome of these studies also supports the continued development to reduce carbon emissions from MDI by replacing propellant to ensure continued availability of spray as a therapeutic option.

* BDP=Beclomethasone DiPropionate; FF=Formoterol Fumarate; GB=Glycopyrronium Bromide