The Safety and Tolerance of Herbal Anti-Angina Drug Compound Danshen Droplet Pill in Healthy Volunteers

摘要

Background: Compound Salvia Pellet (T89), consisting of Danshen (salvia miltiorrhiza), Sanqi (panax notoginseng), and Borneol (Cinnamomum camphora), has been used worldwide for 14 years for chronic angina treatment. Purpose: A dose escalation study to determine the maximum tolerance dose (MTD) in Chinese population to support a proposed dose regimen change.Methods: Forty-six participants (age 18 to 45 yrs, male to female ratio = 1:1) were divided into a series of 6 patients cohorts, and sequentially assigned into one of the escalating dose groups, starting from 540 mg, the clinical doses, until 4 out of 6 subjects experience clinical Adverse Events (AEs) or when the pre-defined 3510 mg dose level is reached and completed. All doses were given orally as a single dose 2 hours after breakfast. Adverse events, vital signs, 12-lead ECG, clinical and laboratory parameters and medical evaluation were conducted as outcome measures. Results: Study completed at the highest pre-defined dose level of 3510 mg dose as never had 4/6 of subject experience AEs in any dose levels studied. All participants completed the study and data were included in the safety analysis. The only moderate AE observation (muscle damage) was observed at 2970 mg dose and was recovered without any medical treatment, and all other AEs (ECG, dizziness, muscle damage) were mild and may (5 cases) or may not (9 cases) be related to testing drug and were all self-resolved within 30 min after dose. Conclusion: Given as single oral dose, Compound Salvia Pellet is safe and well-tolerated up to the 3510 mg studied. The MTD value of Compound Salvia Pellet is unknown from this trial and must be higher than 3510 mg, 13 times higher than its current clinical dose.