Skip to main content
SpringerLink
Log in

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

  • Original Research Article
  • Published:
European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

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 (AUC0–t), the area under the plasma concentration–time curve from time zero to infinity (AUC0–∞), the maximum plasma concentration (Cmax), the time to maximum plasma concentration (Tmax), and the elimination half-life (t1/2). 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 Tmax of 0.34–0.50 h and eliminated slowly with a mean t1/2 ranging from 4.29 to 46.76 h for different dose groups. The Cmax 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 Cmax 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Brozek JL, Bousquet J, Agache I, et al. Allergic rhinitis and its Impact on asthma (ARIA) guidelines—2016 revision. J Allergy Clin Immunol. 2017;140(4):950–8.

  2. Wallace D, Dykewicz M. The diagnosis and management of rhinitis: an updated practice parameter. J Allergy Clin Immunol. 2008;122(Suppl 2):S1–84.

    Article  Google Scholar 

  3. Katelaris CH, Lee BW, Potter PC, et al. Prevalence and diversity of allergic rhinitis in regions of the world beyond Europe and North America. Clin Exp Allergy. 2012;42(2):186–207.

    Article  CAS  Google Scholar 

  4. Grossman J, Banov C, Boggs P, et al. Use of ipratropium bromide nasal spray in chronic treatment of nonallergic perennial rhinitis, alone and in combination with other perennial rhinitis medications. J Allergy Clin Immunol. 1995;95(5 Pt 2):1123–7.

    Article  CAS  Google Scholar 

  5. Haddad EB, Pate H, Keeling JE, et al. Pharmacological characterization of the muscarinic receptor antagonist, glycopyrrolate, in human and guinea-pig airways. Br J Pharmacol. 1999;127(2):413–20.

    Article  CAS  Google Scholar 

  6. Singh S, Loke YK, Furberg CD. Inhaled anticholinergics and risk of major adverse cardiovascular events in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. JAMA. 2009;301(12):1227–30.

    Article  CAS  Google Scholar 

  7. Sun LN, Ding L, Wang YQ, et al. Pharmacokinetics, safety and tolerability of bencycloquidium bromide, a novel selective muscarinic M1/M3 receptor antagonist, after single and multiple intranasal doses in healthy Chinese subjects: an open-label, single-center, first-in-human study. Drugs RD. 2012;12(1):17–28.

    Article  Google Scholar 

  8. US Food and Drug Administration. Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/estimating-maximum-safe-starting-dose-initial-clinical-trials-therapeutics-adult-healthy-volunteers.

  9. China National Medical Products Administration (NMPA). Guidance for estimating the maximum recommended starting dose (MRSD) of drugs in the first clinical trial of healthy adult volunteers. Available from: https://www.nmpa.gov.cn/xxgk/fgwj/gzwj/gzwjyp/20120515120001975.html.

  10. Rudy AC, Coda BA, Archer SM, et al. A multiple-dose phase I study of intranasal hydromorphone hydrochloride in healthy volunteers. Anesth Analg. 2004;99(5):1379–86.

    Article  CAS  Google Scholar 

  11. Christopher T, Lan C, Vincent Y, et al. A review of the important role of CYP2D6 in pharmacogenomics. Genes (Basel). 2020;11(11):1295. https://doi.org/10.3390/genes11111295.

Download references

Acknowledgements

We thank all the subjects who participated in this study and the staff of the drug clinical trial institution, Wuxi People’s Hospital Affiliated with Nanjing Medical University. This study was sponsored by Beijing Shuobai Pharmaceutical Technology Co., Ltd. (Beijing, China).

Author information

Author notes

  1. Nan-nan Chu and Kai Huang contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Drug Clinical Trial Institution, Wuxi People’s Hospital Affiliated with Nanjing Medical University, Wuxi, 214023, Jiangsu, China

    Nan-nan Chu, Kai Huang, Lin-Ling Que, Ying Ding, Xiang-hong Gu, Lin Zhang, Jia-kun Wang & Qing He

  2. Beijing Shuobai Pharmaceutical Technology Co., Ltd., Beijing, China

    Xiao-ping Chen & Zhan-guo Sun

Authors
  1. Nan-nan Chu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kai Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lin-Ling Que
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ying Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiang-hong Gu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jia-kun Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xiao-ping Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Zhan-guo Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Qing He
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qing He.

Ethics declarations

Funding

This study was sponsored and funded by Beijing Shuobai Pharmaceutical Technology Co., Ltd.

Conflicts of Interest

All authors declare no financial support from any organization for the submitted work, no commercial or financial involvements that might present a conflict of interest related to the contribution, and no other activities that influenced the submitted work.

Availability of Data and Material

Basic information about the study is available at: http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml

Code Availability

Not applicable.

Authors’ Contributions

Qing He and Nannan Chu designed the study. Nannan Chu wrote the manuscript and conducted the study with Kai Huang, Lin-Ling Que, Ying Ding, Xianghong Gu, Lin Zhang, and Jiakun Wang. Qing He, Xiao-Ping Chen, and Zhanguo Sun reviewed and gave valuable comments on the manuscript.

Ethics Approval

The study was reviewed and approved by the independent ethics committee of Wuxi People’s Hospital Affiliated with Nanjing Medical University, with the approval number 2020LLPJ-I-70. The study was conducted following International Conference on Harmonization Good Clinical Practice guidelines and applicable regulations governing clinical study conduct, and ethical principles that have their origin in the Declaration of Helsinki.

Consent to Participate

Written informed consent was obtained from all individual participants included in the study.

Consent for Publication

Not applicable.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chu, Nn., Huang, K., Que, LL. et al. 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. Eur J Drug Metab Pharmacokinet 47, 509–521 (2022). https://doi.org/10.1007/s13318-022-00769-6

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13318-022-00769-6

Search

Navigation