Dose-ranging study of a new steroid for asthma: mometasone furoate dry powder inhaler.
A new formulation of mometasone furoate (MF) for administration by dry powder inhaler (DPI) was evaluated for the treatment of asthma. A 12-week, double-blind, placebo-controlled dose-ranging study compared the efficacy and safety of three doses of MF DPI (100, 200 and 400 mcg b.i.d) with beclomethasone dipropionate (BDP) 168 mcg b.i.d. administered by metered dose inhaler in 365 adult or adolescent patients being treated with inhaled glucocorticoids. The mean change from baseline to endpoint (last treatment visit) for forced expiratory volume in 1 sec (FEV1) was the primary efficacy variable. Secondary efficacy variables included other objective measures of pulmonary function [forced vital capacity (FVC), forced expiratory flow 25-75% (FEV25-75%.) and peak expiratory flow rate (PEFR)] as well as subjective measures of therapeutic response (patients' daily evaluation of asthma symptoms and physicians' evaluation). At endpoint, all four active treatments were significantly more effective than placebo (P < 0.01) in improving FEV1 (MF DPI 5 to 7%, BDP 3%, placebo -6.6%) and all other measures of pulmonary function (FVC: MF DPI 4 to 5%, BDP 2%, placebo -4.7%; FEF25-75%: MF DPI 6 to 18%, BDP 7.5%, placebo -9.5%; PEFR (AM): MF DPI 5 to 10%, BDP 5.7%, placebo -7%). A consistent trend was observed for better improvement in patients treated with MF DPI 200 mcg b.i.d. than with MF DPI 100 mcg b.i.d., with no apparent additional benefit of MF DPI 400 mcg b.i.d. Results for the MF DPI 100 mcg b.i.d. and BDP 168 mcg b.i.d. treatment groups were similar. Patients' and physicians' subjective evaluations of symptoms found similar improvement in the MF DPI 200 and 400 mcg b.i.d. treatment groups, which were slightly better than that in the MF DPI 100 mcg b.i.d. group. Symptoms tended to worsen in the placebo group. MF DPI was well tolerated at all dose levels and the most frequently reported treatment-related adverse effects were headache, pharyngitis and oral candidiasis. No evidence of HPA-axis suppression was detected in any treatment group. In summary, all doses of MF DPI were well tolerated and significantly improved lung function and MF DPI 400 mcg (200 mcg b.i.d.) was the optimal dose in this study of patients with moderate persistent asthma.
Bernstein
D I
DI
Bernstein Clinical Research Center, Cincinnati, OH. bernstdd@email.uc.edu
Berkowitz
R B
RB
Chervinsky
P
P
Dvorin
D J
DJ
Finn
A F
AF
Gross
G N
GN
Karetzky
M
M
Kemp
J P
JP
Laforce
C
C
Lumry
W
W
Mendelson
L M
LM
Nelson
H
H
Pearlman
D
D
Rachelefsky
G
G
Ratner
P
P
Repsher
L
L
Segal
A T
AT
Selner
J C
JC
Settipane
G A
GA
Wanderer
A
A
Cuss
F M
FM
Nolop
K B
KB
Harrison
J E
JE
D000293:Adolescent; D000328:Adult; D000368:Aged; D018926:Anti-Allergic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008450:Maximal Midexpiratory Flow Rate / Q000187:drug effects; D008875:Middle Aged; D000068656:Mometasone Furoate; D010366:Peak Expiratory Flow Rate / Q000187:drug effects; D011244:Pregnadienediols; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects
D018926:Anti-Allergic Agents; D000893:Anti-Inflammatory Agents; D011244:Pregnadienediols; D000068656:Mometasone Furoate