No Combretastatin A4 death or serious adverse events (SAEs) were reported during the study and all subjects were in good compliance. No notable mean change from baseline was recorded in the vital signs or

clinical JNJ-26481585 molecular weight laboratory variables. No individual participant value outside the laboratory reference ranges was considered to be clinically significant, and no clinically significant change in ECG and heart rate was reported in any participant during the study. Most subjects reported one or more AE. AEs that occurred in two or more subjects, classified according to the Medical Dictionary for Regulatory Activities system organ class and preferred terms, are listed in table V. The most frequently reported AEs were nasal irritation (including nasal congestion, nasal dryness, redness of nasal mucosa, and epistaxis) and mydriasis. However, the nasal irritation was mild, of limited duration and no inflammation was seen on early or follow-up nasal examinations, while mydriasis was also mild, of limited duration and of no clinical significance. Overall, all the AEs reported were mild in intensity, expected, based on the known activity of the drug or the intranasal route of administration, and not considered to be clinically significant. There was no trend for increasing AEs with increasing doses over the dose

range evaluated. Table V Treatment-emergent MRT67307 adverse events occurring in two or more subjects (safety population, n = 58) Discussion At present, the ADP ribosylation factor anticholinergic medications used in the treatment of airway diseases are not selective for muscarinic receptor subtypes.[23] The novel selective muscarinic M1/M3 receptor antagonists, such as aclidinium bromide[24] and penehyclidine hydrochloride,[25,26] are under development for the therapy of chronic obstructive pulmonary disease (COPD), while the novel agents under development for the treatment of rhinorrhea in rhinitis are limited. BCQB is under development not only for the treatment of rhinorrhea

in rhinitis but also for the therapy of COPD.[7,11] The aerosol with quantitative inhalation of bencycloquidium bromide[27] is under development. The objective of this FIH study was to assess the pharmacokinetics, safety and tolerability after single and multiple intranasal doses of BCQB in healthy Chinese subjects. Following single intranasal doses in healthy Chinese adult subjects, BCQB was rapidly absorbed, the plasma concentration of BCQB decreased in a biphasic manner, the Cmax and AUC of BCQB increased in proportion to the studied doses, and the mean t1/2 and the mean CL/F were independent of the administered doses. The mean t1/2 of the studied dose groups ranged from 7.4 to 10.7 hours.