The safety and tolerability of alkaloids from Alstonia scholaris leaves in healthy Chinese volunteers: a single-centre, randomized, double-blind, placebo-controlled phase I clinical trial

• Published in: Pharmaceutical biology Vol. 59; no. 1; pp. 482 - 491
• Main Authors: Gou, Zhong-Ping, Zhao, Yun-Li, Zou, Lin-Ling, Wang, Ying, Shu, Shi-Qing, Zhu, Xiao-Hong, Zheng, Li, Shen, Qi, Luo, Zhu, Miao, Jia, Wang, Yong-Sheng, Luo, Xiao-Dong, Feng, Ping
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2021; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: Adult; Adverse events; Alkaloids; Alkaloids - administration & dosage; Alkaloids - adverse effects; Alkaloids - isolation & purification; Alstonia - chemistry; Alstonia scholaris; Asian People; Asthma; Bilirubin; Bronchitis; Clinical safety; Clinical trials; Cohort Studies; Cough; Distension; Doppler effect; dose-escalation study; Dose-Response Relationship, Drug; Double-Blind Method; Double-blind studies; Drug dosages; EKG; Female; healthy subject; Humans; Inflammation; Laboratories; Male; Metabolism; Metabolites; Natural products; Nausea; Placebos; Plant Leaves; R&D; Research & development; Safety; Toxicity; Young Adult; Clinical safety; dose-escalation study; healthy subject
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2021.1893349

Capsule of alkaloids from the leaf of Alstonia scholaris (L.) R.Br. (Apocynaceae) (CALAS) is a new investigational botanical drug (No. 2011L01436) for bronchitis, post-infectious cough and asthma. To observe the clinical safety and tolerability of CALAS. Subjects were assigned to eight cohorts, and each received randomly CALAS or placebo in one of single ascending dose (SAD) of 8, 40, 120, 240, 360, 480, or in one of multiple ascending dose (MAD) of 40 or 120 mg, three times daily for 7 days. Each cohort contained two placebo subjects. Sixty-two enrolled volunteers completed the study and no serious adverse events and clinically significant changes in vital signs, electrocardiography, and upper abdominal Doppler ultrasonography were observed. The ratios of treatment-emergent adverse events (TEAEs) were reported in 11/46 (23.91%) of CALAS groups and 3/16 (18.75%) of the placebo group (p > 0.05), respectively, based on the results of SAD and MAD. All TEAEs were mild, transient, and disappeared without any intervention. The TEAEs possibly related to CALAS treatment were as followings: hiccups (4/46: 8%), dry mouth and nausea (3/46: 6%), increased sleep (2/46: 4%), abdominal distension (1/46: 2%), bilirubin elevated (1/46: 2%). CALAS is safe and well-tolerated with no unexpected or clinically relevant safety concerns up to a single dose of 360 mg and three times daily for 7 days up to 120 mg in healthy Chinese volunteers, supporting further Phase II studies.