Safety, Tolerability, and Pharmacokinetic Study of 101BHG-D01 Nasal Spray, a Novel Long-Acting and Selective Cholinergic M Receptor Antagonist, in Healthy Chinese Volunteers: A Randomized, Double-Blind, Placebo-Controlled, Single-Dose Escalation, First-In-Human Study

101BHG-D01 nasal spray is the first novel long-acting cholinergic M receptor antagonist under development to treat rhinorrhea in rhinitis. This first-in-human study aimed to evaluate the safety, tolerability, and pharmacokinetics of 101BHG-D01 nasal spray following single intranasal doses in healthy Chinese subjects.

A randomized, double-blind, placebo-controlled, single-dose escalation study was conducted in healthy Chinese volunteers after intranasal doses of 101BHG-D01 nasal spray or placebo ranging from 40 µg to 960 µg (total of six doses). Blood samples were collected at scheduled time points, and plasma concentrations were determined using a validated high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS) method. A non-compartmental method was used to calculate the main pharmacokinetic parameters, including the area under the plasma concentration–time curve from time zero to the time of the last measurable concentration (AUC_0–t), the area under the plasma concentration–time curve from time zero to infinity (AUC_0–∞), the maximum plasma concentration (C_max), the time to maximum plasma concentration (T_max), and the elimination half-life (t_1/2). Safety was evaluated by monitoring adverse events, laboratory assays, vital signs, physical examinations, 12-lead electrocardiograms (ECGs), anterior rhinoscopy, ophthalmic examination, and ambulatory ECG monitoring.

Following single intranasal dosing, 101BHG-D01 was rapidly absorbed with a median T_max of 0.34–0.50 h and eliminated slowly with a mean t_1/2 ranging from 4.29 to 46.76 h for different dose groups. The C_max and AUC of 101BHG-D01 increased linearly across the examined dose range of 40–960 µg. 101BHG-D01 nasal spray was well tolerated, all AEs were mild, and no serious adverse events occurred during the study.

101BHG-D01 nasal spray was safe and well tolerated in healthy Chinese subjects when administered intranasally in single escalating doses. The mean C_max and AUC increased proportionally to the studied dose. The pharmacokinetic, safety, and tolerability profiles of 101BHG-D01 nasal spray indicate that it is a good candidate for further development as a treatment for rhinorrhea in rhinitis.