A Multicenter, Double-blind, Randomized and Placebo-controlled Pivotal Phase 3 Study to Evaluate the Safety and Efficacy of T89 in the Prevention and Treatment of Acute Mountain Sickness (AMS) After Rapid Ascent
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 853
- 试验地点
- 3
- 主要终点
- Change of baseline corrected mean LLSS score on Day 4 morning (next mornings after arrival at high altitude) between T89 and placebo groups.
研究概览
简要总结
The specific aim of this double blind, randomized phase III trial is to evaluate the safety and efficacy of T89 in preventing Acute Mountain Sickness (AMS) and relieving the symptoms of AMS after rapid ascent.
详细描述
Acute mountain sickness (AMS) is a common ailment in people venturing over 2,500 meters altitude. It is a pathological effect of high altitude on humans, caused by acute exposure to low partial pressure of oxygen at high altitude. It presents with a cluster of nonspecific symptoms including headache and one of the following: gastrointestinal symptoms, fatigue and/or weakness, dizziness/ lightheadedness or difficulty sleeping.
T89 capsule is a modernized industrialized version of a traditional Chinese herbal medicine. It is a botanical drug product for oral use. Previous clinical studies showed T89 has substantial benefits in the prevention or amelioration of symptoms associated with acute mountain sickness (AMS).This is double-blind, randomized, placebo controlled pivotal phase 3 study. After informed consent is obtained, eligible subjects will be randomized to one of the 3 study groups (T89 high dose, T89 low dose and placebo control). The study drug will be given orally for 5 days (2 days at sea level and 3 days at high altitude). The clinical assessment of Lake Louise Scoring System (LLSS), blood oxygen saturation, the exercise tolerance, blood pressure and heart rate will be performed at sea level and altitude. A total of 846 subjects will be enrolled with 282 subjects in each treatment arm, and a minimum of 756 subjects are expected to complete the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers: ages 18 - 55 years old;
- •Primary residence elevation of 2,461 ft (750m) or lower;
- •Not ascending to altitude >10,000 ft within 4 months prior to screening;
- •Females of childbearing potential must have a negative pregnancy test and established on a method of contraception that in the investigator's opinion is acceptable. Females must agree to remain on their established method of contraception from the time of the screening visit and throughout the study period;
- •Willing to participate voluntarily and sign a written informed consent.
排除标准
- •Subjects with medical history of cardiovascular, cerebrovascular diseases or asthma; uncontrolled hypertension with SBP>140 and or DBP>90 mmHg;
- •Subjects with current and clinically significant respiratory system disease, digestive disease, liver disease, central nervous system disease, psychiatric disease, metabolic disease, renal disease, acute infection or anemia, or who test positive for COVID-19 (COVID testing will be performed, not per study requirement, but in compliance with local law or policy, and subject with known positive for COVID-19 will be excluded).
- •Total LLSS score (LLSS score) is ≥2 at any check point during screening period;
- •Blood oxygen saturation (SpO2), preferably tested on the left-hand index finger, is less than 95% at screening visits;
- •Subjects with abnormal renal or liver function with clinical significance (ALT or AST > 2×ULN, Creatinine > ULN) at screening visit;
- •Subjects with CRP > ULN at screening visit;
- •Subjects with primary (migraine, tension-type headache, and cluster headache etc.) or secondary headaches (headache related to infection, vascular disease etc.) within one month at screening;
- •Surgery or blood donation within 3 months prior to screening;
- •On treatment of any medications (including any dietary supplements) except for birth control within 14 days prior to screening and throughout the study period;
- •Smokers who had a habit of smoking during the last 4 months prior to the starting of screening;
- •Contradictive to treatment of Danshen (Radix Saliva Miltiorrhize Bge., RSM) products;
- •Women who are pregnant or lactating.
- •Substance abuse. Subjects with a recent (within the last 6 months) history of substance abuse (alcohol, marijuana, or known drug dependence). Or subjects who have a positive urine substance test at screening;
- •Participation in any other interventional clinical trial or on an investigational drug within 30 days prior to screening;
- •A family member or relative of the study site staff;
- •Any condition that, in the opinion of the investigator, is likely to prevent compliance with the study protocol, interfere with the assessment, or pose a safety concern if the subject participates in the study at screening.
研究组 & 干预措施
T89 low-dose group
Subjects in this group will take three T89 capsules and one Placebo capsule each time by oral administration three times daily for 5 days.
干预措施: T89 capsule (Drug)
T89 low-dose group
Subjects in this group will take three T89 capsules and one Placebo capsule each time by oral administration three times daily for 5 days.
干预措施: Placebo capsule (Drug)
T89 high-dose group
Subjects in this group will take four T89 capsules each time by oral administration three times daily for 5 days.
干预措施: T89 capsule (Drug)
Placebo group
Placebo capsule does not contain any amount of active substance. Subjects in this group will take four placebo capsules each time by oral administration three times daily for 5 days.
干预措施: Placebo capsule (Drug)
结局指标
主要结局
Change of baseline corrected mean LLSS score on Day 4 morning (next mornings after arrival at high altitude) between T89 and placebo groups.
时间窗: Baseline and day 4
2018 Lake Louise Scoring System (LLSS) score \[0-12\] will be used in this primary outcome assessment. The higher LLSS scores mean the worse symptoms of AMS. Baseline will be the average of LLSS scores on Day 2 and the one on Day 3 before breakfast.
次要结局
- The change of exercise tolerance at high altitude (on Day 3 after arriving and Day 5, respectively) from those of at sea level baseline between T89 and placebo groups.(Baseline and days 3 and 5)
- The change of the symptom-related AE drop-out rate between T89 and placebo groups.(Days 3-6)
- The change of heart rate (beats/minute) at high altitude from those of at sea level baseline on Day 1 (prior to the first dose administration) between T89 and placebo groups.(Screening day, days 2-6)
- The change of blood oxygen saturation levels (SpO2) at high altitude between T89 and placebo groups.(Baseline and days 3-6)
- The change of the area under the curve (AUC) of baseline corrected LLSS score-time profile between T89 and placebo groups.(Baseline and days 3-6)
- The change of total functional LLSS score at any given time points between T89 and placebo groups.(Baseline and days 3-6)
- The change of percentage reduction of the daily total LLSS score from Day 4 to Day 5 between T89 and placebo groups.(Days 4-5)
- The change of baseline corrected LLSS score at any given time points between T89 and placebo groups.(Baseline and days 3-6)
- The change of blood pressure (mmHg) during at high altitude from those of at sea level baseline on Day 1 (prior to the first dose administration) between T89 and placebo groups.(Screening day, days 2-6)
- The change in total incidence of LLSS score ≥5 on Day 4 morning between T89 and placebo groups.(Day 4 morning)
- Accumulated incidence rate of subjects who underwent any rescue activity in transit and after ascending between T89 and placebo groups.(Days 3-6)