Tianshili: release the results of phase III clinical trial of Compound Danshen Dropping Pills in FDA international multi center

Recently, compound Danshen dropping pill, the exclusive product of Tianshili Pharmaceutical Group Co., Ltd which has been listed in China, is a global multi center randomized double blind large sample phase III clinical trial for applying for FDA's approval of new drug listing in the United States After a series of data management and statistical analysis, the top level analysis summary report of clinical trial (hereinafter referred to as "the report") has been formed Notice ") In accordance with the relevant provisions of the guidelines for industry information disclosure of listed companies No 7 - pharmaceutical manufacturing of Shanghai Stock Exchange, the relevant contents are hereby announced 1、 Conclusion the top-line analysis of the main clinical end points of the trial of "t89-07-caesa" was completed recently Now, the results of phase III clinical research in 127 centers in 9 countries are announced as follows: 1 Compound Danshen dropping pill has a significant dose effect relationship at the main clinical end point, and the effect of increasing Ted is significantly better than that of placebo control group and Sanqi borneol group In the first four weeks of clinical study, the effect of high and low dose of Compound Danshen Dropping Pill plus Ted was similar in patients with more severe stable angina pectoris with various types of ECG abnormalities, excluding individual cases whose research data could not be used due to force majeure (such as the national war and the closure of the center) Then to the sixth week, the high dose group continued to increase with the time of taking medicine At the end of the sixth week, the point-to-point comparison showed that the effect of high-dose group was higher than that of low-dose group, and both groups were significantly better than that of placebo control group and Sanqi borneol group (P < 0.05) It was superior to placebo group and Sanqi borneol group (P < 0.05) 2 The secondary efficacy observation end-point indicators support the main clinical end-point indicators, and the efficacy evidence is in a chain After the 4-week treatment period, compared with the placebo group, the high-dose and low-dose group of Compound Danshen dropping pill can reduce the use of nitroglycerin by 25% every two weeks, which is about 9% higher than that of the placebo group during this period Compared with the placebo group, the high-dose and low-dose group of Compound Danshen dropping pill can also significantly reduce the number of angina attacks per two weeks by 27%, and only reduce the number of angina attacks by 0.001% compared with the placebo group 3 For the first time, the large-scale randomized double-blind international multi center phase III clinical trial method was used in this experiment The curative effect of high-dose group of Compound Danshen dropping pill was significantly better than that of its counterpart group of Sanqi borneol The composition basis of Compound Danshen dropping pill was interpreted by clinical research, which satisfied the research and development of compound Chinese medicine Drug administration management requirements that need to be studied 4 Since there is no obvious difference in the efficacy of the trial with different batches of Compound Danshen dropping pills, the effective substance control range of three batches of production samples used in phase III clinical can be used as the basis for the quality standard of the products on the market 5 This experiment proved the clinical safety of Compound Danshen Dropping Pill again There were no serious adverse events related to the test protocol or compound Danshen Dropping Pills during the whole test period All other general adverse events were low frequency, mild and self-healing There was no difference in the incidence of adverse events between different study groups On the basis of the safety evidence of preclinical experimental animals such as acute toxicity and long toxicity and the clinical safety pharmacology evidence of healthy volunteers' dose climbing, the clinical use safety of Compound Danshen Dropping Pill under the high dose condition of this experiment was verified The safety and efficacy of Compound Danshen Dropping Pill in FDA phase II clinical trial of chronic stable angina pectoris were further verified 2、 Research and development of Compound Danshen dropping pill and related information Compound Danshen dropping pill is a kind of drug developed exclusively by our company to treat cardiovascular diseases It obtained the national new drug certificate and production approval document in 1993 and was put on the market in 1995 It is a national medical insurance variety, national basic drug catalog variety and national basic drug low price drug catalog variety As a famous brand of modern Chinese medicine, a large number of consumers use and benefit from it every year On September 29, 1998, Fufang Danshen Dropping Pill officially passed the application for clinical medication (ind) of the US Food and Drug Administration (FDA) as a drug In 2006, the company reapplied a new ind to FDA and determined the clinical indications for the prevention and treatment of chronic stable angina The drug code of Compound Danshen dropping pill used in clinical research institute was T89 The phase II clinical trial was prepared from February 2007 Since November 2008, the first group of patients was enrolled into the group Clinical trials involving multiple dose, randomized double-blind, multicenter parallel control and other aspects were carried out in clinical centers in 11 states such as Florida and Texas At the beginning of 2010, the phase II clinical trial was completed On August 7, 2010, according to the phase II clinical trial report of the United States (T89), the company issued the suggestive announcement on publishing the phase II clinical trial results of the United States After two years of preparation, the FDA phase III clinical trial of Compound Danshen Dropping Pills (T89) was officially started in August 2012 The phase III clinical study of T89 was designed as a double-blind, randomized, multi-national, multicenter, placebo-controlled and double control clinical study to evaluate the safety and efficacy of Compound Danshen Dropping Pills (T89) in patients with chronic stable angina Based on the evidence of batch difference and dose-response relationship in clinical research, the reference standard for quality control of mass production products is established The phase III clinical trial project was carried out in 127 clinical centers in 9 countries / regions of the United States, Canada, Russia, Ukraine, Georgia, Belarus, Mexico, Brazil and Taiwan The clinical work was completed in March 2016, and then it entered the cov (Clinical Center closing visit), database locking stage, and then the top of the research data was carried out Layer analysis, and recently completed the report In view of the fact that compound Danshen Dropping Pill (T89) is the world's first compound Chinese medicine in overseas research and development and completed the third phase of clinical research, which has many cutting-edge and innovative features, especially the originality of dropping pill formulation in the international new drug application, it will still need to be improved under the guidance of FDA According to the FDA's prompt in the recent face-to-face meeting, before submitting the listing application to the FDA of the United States, it is also necessary to carry out a detailed hierarchical statistical analysis of the treatment time, dose, background drug use, drug use and other factors of the phase III clinical study, and conduct subsequent written and face-to-face discussions with the FDA The accumulated R & D investment of the fda-nda (new drug application) project of Compound Danshen Dropping Pills (T89) will be disclosed timely after collection, sorting and statistics 3 The market situation of similar drugs in the United States: angina pectoris is a clinical syndrome caused by acute and temporary imbalance of oxygen supply and oxygen demand Its clinical feature is paroxysmal chest squeezing pain sensation, mainly located in the back of sternum, which can radiate to the precordial area, left upper limb, neck, left shoulder and back It is often found in the time of tiredness or emotional excitement, lasting for several minutes After rest or nitrate preparation, the above symptoms disappear rapidly Angina can be divided into three clinical types: stable angina, unstable angina and variant angina Its stability includes two meanings: one is the stability of the condition; the other is the stability of the atherosclerotic plaque, without unstable factors such as ulcer rupture, dissection and thrombosis The pathological basis of stable angina is fixed stenosis caused by coronary atherosclerotic plaque Chronic stable angina pectoris refers to the patients whose degree, frequency, nature and inducing factors of angina pectoris have no significant change in a few weeks In 2012, there were 8.2 million chronic angina patients in the United States, accounting for 2.6% of the total population of the country, and about 565000 newly diagnosed patients were added every year IV comparison with the conclusions of clinical trials of similar products After nearly 20 years of research work for FDA new drug declaration in the United States, compound Danshen Dropping Pill (T89) has been tested by strict clinical trials in the world It is the first compound Chinese medicine preparation in the world to complete the FDA phase III randomized, double-blind, international multi center large-scale clinical trials At present, the market of chronic angina pectoris in the United States is chemical products, and there is no comparable product.