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

Background and Objective 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. Methods 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. Results 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. Conclusions 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.