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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
853
T89 capsule (trade name Dantonic®) is a botanical drug containing 75mg active substance which is the water extract of Danshen and Sanqi. T89 capsules, p.o. TID.
Placebo capsules, p.o. TID.
Hypoxia Research Lab, UCSF Parnassus Campus, S-256
San Francisco, California, United States
Affiliated Hospital of Chengdu University of TCM
Chengdu, Sichuan, China
Tibet Autonomous Region People's Hospital
Lhasa, Tibet, China
Change of baseline corrected mean LLSS score on Day 4 morning (next mornings after arrival at high altitude) between T89 and placebo groups.
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.
Time frame: Baseline and day 4
The change of blood oxygen saturation levels (SpO2) at high altitude between T89 and placebo groups.
Blood oxygen saturation (SpO2) will be measured by pulse oximeter at sea level (on screening day, Day 2 and Day 3 morning) and at high altitude (Day 3 after arriving and Day 4-Day 6).
Time frame: 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.
AUC of based corrected LLSS score-time curve during altitude stay will be compared between T89 and placebo groups.
Time frame: Baseline and days 3-6
The change in total incidence of LLSS score ≥5 on Day 4 morning between T89 and placebo groups.
Total incidence of LLSS score ≥5 will be recorded on Day 4 morning. The difference between T89 and placebo groups will be compared.
Time frame: Day 4 morning
The change of percentage reduction of the daily total LLSS score from Day 4 to Day 5 between T89 and placebo groups.
Proportional reduction of the daily total LLSS score from Day 4 to Day 5 at high altitude will be compared between T89 and placebo groups.
Time frame: Days 4-5
The change of baseline corrected LLSS score at any given time points between T89 and placebo groups.
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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 corrected LLSS score will be assessed at every time points at high altitude from Day 3 to Day 6.
Time frame: Baseline and days 3-6
The change of total functional LLSS score at any given time points between T89 and placebo groups.
The functional score \[0-3\] will be self-reported using the 1993 Lake Louise Acute Mountain Sickness Score System to evaluate how did AMS symptoms affect subjects' activities, if they have AMS symptoms. The higher functional scores mean the worse symptoms of AMS.
Time frame: Baseline and days 3-6
Accumulated incidence rate of subjects who underwent any rescue activity in transit and after ascending between T89 and placebo groups.
The total incidence of subjects who received rescue medicine, oxygen or descent to lower level will be recorded in transit and after arriving high altitude.
Time frame: Days 3-6
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.
Exercise tolerance test will be performed on bicycle ergometer.
Time frame: Baseline and days 3 and 5
The change of the symptom-related AE drop-out rate between T89 and placebo groups.
The symptom-related AE drop-out rate is proportion of participants who dropped out study because of adverse event.
Time frame: 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.
Unit of blood pressure is mmHg. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) will be recorded. Blood pressure will be measured at each applicable visit during the whole study period (screening day, Day 2-Day 6).
Time frame: Screening day, days 2-6
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.
Unit of heart rate is beats/minute. Heart rate will be measured at each applicable visit during the whole study period (screening day, Day 2-Day 6).
Time frame: Screening day, days 2-6