Randomized equivalence trial: A novel multidose dry powder inhaler and originator device in adult and adolescent asthma.

BACKGROUND: Guideline-defined asthma control can be achieved and maintained in patients by treatment with fluticasone propionate-salmeterol (FP-Sal). OBJECTIVE: To compare the efficacy and safety of FP-Sal delivered via a novel multidose dry powder inhaler (mDPI) versus an originator device in adolescent and adult patients with moderate-to-severe persistent asthma. METHODS: Patients ages 12-65 years (N = 555) were randomized to treatment with FP-Sal novel mDPI 100 µg-50 µg or 500 µg-50 µg, or originator device 100 µg-50 µg or 500 µg-50 µg in a double-blind, double-dummy, parallel-group, multicenter study. Primary efficacy measures were absolute change in forced expiratory volume in 1 second (FEV1) from baseline and the area under the 12-hour serial FEV1 curve at the end of 12 weeks of treatment. Secondary end points included mean changes in FEV1; FEV1 % predicted; morning predose peak expiratory flow; daytime, nighttime, total asthma symptom scores; rescue medication use; percentage of patients with guideline-defined controlled asthma; global efficacy evaluation; patients' device preference; and safety. RESULTS: FP-Sal mDPI and originator device-mediated increases in FEV1 from baseline to the end of treatment were not significantly different, difference in least squares mean, -0.065 L (95% confidence interval, -0.154 to 0.024 L) at 100 µg-50 µg, and -0.032 L (95% confidence interval, -0.121 to 0.057 L) at 500 µg-50 µg). Both doses of FP-Sal mDPI improved FEV1 area under the 12-hour serial FEV1 curve from baseline and all secondary efficacy measures with no significant differences from the originator device at equivalent doses, with similar safety profiles. CONCLUSIONS: FP-Sal mDPI demonstrated equivalent efficacy and safety profile to the originator device and is an alternative in this patient group.

Colocalization but differential regulation of neuronal NO synthase and nicotinic acetylcholine receptor in C2C12 myotubes.

In mammalian skeletal muscle, neuronal-type nitric oxide synthase (nNOS) is found to be enriched at neuromuscular endplates. Here we demonstrate the colocalization of the nicotinic acetylcholine receptor (nAChR, stained with alpha-bungarotoxin) and nNOS (stained with a specific antibody) in murine C(2)C(12) myotubes. However, coimmunoprecipitation experiments demonstrated no evidence for a direct protein-protein association between the nAChR and nNOS in C(2)C(12) myotubes. An antibody to the alpha(1)-subunit of the nAChR did not coprecipitate nNOS, and an nNOS-specific antibody did not precipitate the alpha(1)-subunit of the nAChR. Treatment of mice with bacterial LPS downregulated the expression of nNOS in skeletal muscle, and treatment of C(2)C(12) cells with bacterial LPS and interferon-gamma markedly decreased nNOS mRNA and protein expression. In contrast, mRNA and protein of the nAChR (alpha-, gamma-, and epsilon-subunits) remained unchanged at the mRNA and protein levels. These data demonstrate that nNOS and the nAChR are colocalized in murine skeletal muscle and C(2)C(12) cells but differ in their expressional regulation.