PURPOSE: Dysphonia and oral candidiasis are 2 local adverse events (AEs) commonly associated with inhaled corticosteroid (ICS) use. We assessed the incidence of these 2 AEs by analyzing data from 6 phase III studies of mometasone furoate/formoterol (MF/F) administered via a pressurized metered-dose inhaler (MDI), an investigational ICS/long-acting β2-agonist combination product.
METHODS: Incidences of dysphonia and oral candidiasis were assessed in all 6 phase III MF/F persistent asthma trials conducted to date: 1) study P04703: n=343, 4 weeks, open-label, 2-week compliance period on MF/F[100/10μg], MF/F=100/10μg; 2) study P04705: n=722, 12 weeks, open-label, 2−4-week run-in on MF[200μg], MF/F=200/10μg, fluticasone propionate/salmeterol dry powder inhaler (FP/S-DPI)=250/50μg; 3) study P04431: n=728, 12 weeks, double-blind, 2−4-week run-in on MF[400μg], MF/F=200/10μg, MF/F=400/10μg, MF=400μg; 4) study P04073: n=746, 26 weeks, double-blind, 2−3-week run-in on MF[100μg], MF/F=100/10μg, MF=100μg, F=10μg, placebo; 5) study P04334: n=781, 26 weeks, double-blind, 2−3-week run-in on MF[200μg], MF/F=200/10μg, MF=200μg, F=10μg, placebo; 6) study P04139: n=404, 52 weeks, open-label, MF/F=200/10μg, MF/F=400/10μg, FP/S-MDI=250/50μg, FP/S-MDI=500/50μg. All subjects (≥12 y) received twice daily (BID) treatment. All studies were approved by an institutional review board, and all subjects provided informed consent.
RESULTS: Incidences of treatment-emergent dysphonia in each treatment group were: study P04703: MF/F[100/10μg]=0.3%; study P04705: MF/F[200/10μg]=3.8%, FP/S-DPI[250/50μg]=3.7%; study P04431: MF/F[200/10μg]=0%, MF/F[400/10μg]=0.8%, MF[400μg]=1.3%; study P04073: MF/F[100/10μg]=0.6%, MF[100μg]=0.5%, F[10μg]=0.5%, placebo=0.5%; study P04334: MF/F[200/10μg]=1.0%, MF[200μg]=0.5%, F[10μg]=0.5%, placebo=0.5%; study P04139: MF/F[200/10μg]=5.0%, MF/F[400/10μg]=3.8%, FP/S-MDI[250/50μg]=7.4%, FP/S-MDI[500/50μg]=3.1%. Incidences of treatment-emergent oral candidiasis in each treatment group were: study P04703: MF/F[100/10μg]=2.0%; study P04705: MF/F[200/10μg]=0%, FP/S-DPI[250/50μg]=0.9%; study P04431: MF/F[200/10μg]=0.4%, MF/F[400/10μg]=0.8%, MF[400μg]=0.8%; study P04073: MF/F[100/10μg]=0.5%, MF[100μg]=0.5%, F[10μg]=0%, placebo=0%; study P04334: MF/F[200/10μg]=1.0%, MF[200μg]=0.5%, F[10μg]=1.0%, placebo=0.5%; study P04139: MF/F[200/10μg]=1.4%, MF/F[400/10μg]=0.8%, FP/S-MDI[250/50μg]=1.5%, FP/S-MDI[500/50μg]=3.1%.
CONCLUSION: Data from 6 clinical trials indicate that the incidences of dysphonia and oral candidiasis associated with the three MF/F dosing strengths investigated are comparable to those observed with standard doses of MF, F, and FP/S. No dose relationship with respect to these AEs and MF/F was observed.
CLINICAL IMPLICATIONS: When assessed for local AEs, MF/F treatment was safe and did not demonstrate increased local AE frequency.
DISCLOSURE: Steven Weinstein, Grant monies (from industry related sources) Dr. Nathan has received grants and research support from Abbott, Alcon, AstraZeneca, Ception, Dey, Dyax, Genentech, GlaxoSmithKline, MAP, MedImmune, Novartis, Sanofi-Aventis, Schering-Plough, and TEVA.Dr. Meltzer received research/grant support and served as a consultant and on speaker bureau for Schering-Plough.Dr. Weinstein has received grants from Schering-Plough, Merck, GSK, Amgen, and Novartis, served on Advisory Boards for GSK, Schering-Plough, and Sepracor and participated in Speaker’s Bureaus for Teva, Schering-Plough, Merck, Sanofi-Aventis, and Astra-Zeneca.; Employee Hendrik Nolte is a full time employee of Merck Research Laboratories; Consultant fee, speaker bureau, advisory committee, etc. Dr. Nathan has served as consultant or scientific advisor for Genentech, GlaxoSmithKline, Merck, Novartis, Schering-Plough, and TEVA. He has also participated in Speaker’s Bureaus for AstraZeneca, Genentech, GlaxoSmithKline, Novartis, Sanofi-Aventis, Schering-Plough and UCB. Dr. Maspero, GSK; Novartis; Schering Plough; Investigator; GSK; Merck; Novartis; AZ; Schering Plough; AZ; Advisory Board/Speaker; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Mometasone furoate/formoterol is a new ICS/LABA combination treatment currently under review by the US Food and Drug Administration as a potential new treatment for persistent asthma.