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Context: 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., Objective: To observe the clinical safety and tolerability of CALAS., Materials and Methods: 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., Results: 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%)., Discussion and Conclusions: 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.

Background: Alstonia scholaris (Apocynaceae) was reported to be a rich source of indole alkaloids, which exhibited remarkably bioactivities. The leaf of A. scholaris has been used in 'dai' ethno-medicine for treatment of respiratory diseases, and the defined indole alkaloids from leaf of A. scholaris has been registered as investigational new botanical drug (No. 2011L01436) and was approved for phase I/II clinical trials by China Food and Drug Administration (CFDA)., Purpose: The aim of the trial is to evaluate the safety and explore the relationship of dosing frequency and pharmacokinetics after oral administration of capsule of alkaloids from leaf of A. scholaris (CALAS) at different doses., Methods: In this randomized, open-labelled, single-center clinical trial, the safety and pharmacokinetics of CALAS were assessed in eligible healthy Chinese volunteers after oral administration of different doses. Each volunteer (n = 10 per group) received single dose of CALAS from 20 mg, 40 mg, 80 mg to 120 mg orally. The pharmacokinetics of CALAS was investigated in healthy Chinese subjects' plasma by a fully-validated LC-MS/MS method. Safety was assessed biochemically and clinically throughout the study, and drug re-excitation research was conducted to verify the correlation between investigational product and minor adverse events. The trial was registered on August 26, 2015 (http://www.chictr.org.cn/showproj.aspx?proj=11736), number ChiCTR-IPR-15006976., Results: 40 subjects completed the study, and as a result, vallesamine had the highest concentration in plasma of healthy volunteers, and the AUC exposure level in each compounds in turn is vallesamine > scholaricine > 19-epischolaricine > picrinine. For the safety evaluation of CALAS, two cases of minor adverse events were observed during the trial, but the drug re-excitation research indicated that these two adverse events were related to the individual's physiological variation., Conclusion: Pharmacokinetic characteristics of each ingredient showed different patterns. 19-epischolaricine, vallesamine and picrinine were match to the linear pharmacokinetic characteristics, but scholaricine conformed to the characteristics of nonlinear pharmacokinetics. The CALAS was safe in healthy subjects under the current dose regimen., (Copyright © 2019. Published by Elsevier GmbH.)

Alstonia scholaris could be used as a traditional medicinal plant in China for the treatment of acute respiratory, which might be caused by respiratory tract infections. The investigation tested the anti-infective effects of total alkaloids extract (TA) from leaves of A. scholaris, and as a result, TA inhibited herpes simplex virus type 1 (HSV-1), respiratory syncytial virus (RSV) and influenza A virus (H1N1) in vitro respectively. In addition, the survival days of mice were prolonged, and the lung weights and mortality of mice were decreased significantly, after oral administrated TA in H1N1 and beta-hemolytic streptococcus infectious models in vivo respectively. The finding supported partly the traditional usage of A. scholaris in the treatment of respiratory infections. [ABSTRACT FROM AUTHOR]