T89 in Prevention and Treatment of Acute Mountain Sickness (AMS) During Rapid Ascent

Acute mountain sickness (AMS) is a common ailment in people venturing over 2500 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 as a collection of nonspecific
symptoms, acquired at high altitude or in low air pressure, including headache and one of the
following: gastrointestinal symptoms, fatigue and/or weakness, dizziness/ lightheadedness or
difficulty sleeping. Severity and incidence of these conditions depend on the rate of ascent,
elevation obtained, duration of altitude exposure, physical exertion, and inherent genetic
susceptibility. Pilgrims to high altitudes are at an added risk since they are unaware and
they gain height faster than the recommendations. The underlying pathophysiology of AMS
remains poorly defined, but some data support the role of increased fluid retention, which
may contribute to cerebral over perfusion, endothelial leakage, and eventual subclinical
cerebral edema.

T89 capsule is a modernized industrialized version of a traditional Chinese herbal medicine.
It is a botanical drug product for oral use. The drug substance is the water extract of
Danshen (Radix Saliva Miltiorrhiza Bge., RSM) and Sanqi (Radix Notoginseng, RN). T89 capsule
also contains Bingpian (Borneol) which is acting as an absorption enhancer.

T89 is currently used internationally for the treatment of chronic stable angina pectoris due
to coronary heart disease. T89 was approved for marketing as a drug by China Food and Drug
Administration (CFDA) in 1993. The estimated exposure population is more than 240 million
person·month calculated by sales data from 1995 to 2016. The global market of T89 is
continuously expanding. Since the first launch in Vietnam in 2000, Cardiotonic Pill and
Cardiotonic Capsule have been legally marketed in 32 countries or regions as prescription
drug, OTC, dietary supplement, or complementary medicine. For overseas market, the estimated
exposure population is about 1 million person·month calculated by sales volume.

In the United States, T89 was approved as an investigational new drug indicated for the
prevention and treatment of the reoccurrence of angina pectoris in patient with confirmed
chronic stable angina in 2006. A pivotal global Phase 3 clinical study was completed in 2016,
with a total 1004 patients enrolled in 7 countries.

In recent years, several literatures and clinical studies have demonstrated that T89 showed
substantial benefits in the prevention or amelioration of symptoms associated with acute
mountain sickness (AMS), including nausea, vomiting, headache, dizziness, fatigue, and sleep
disturbance. Such efficacy was also verified in terms of AMS incidence rate and symptom
severity from a recent pilot clinical study conducted by the sponsor in Tibet, China.

Inclusion Criteria:

1. Healthy volunteers: ages 18 - 55 years old;

2. Primary residence elevation of 1,000 ft or lower;

3. Not ascending to altitude >10,000 ft or higher within 4 months prior to screening;

4. Females of childbearing potential must have a negative pregnancy test, not be breast
feeding, 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.

5. Willing to participate voluntarily and to sign a written informed consent.

Exclusion Criteria:

1. Subjects with medical history of cardiovascular, cerebrovascular diseases or asthma;

2. Subjects with clinically significant respiratory system disease, digestive disease,
mental disease, metabolic disease, acute infection or anemia;

3. Total LLSS self-assessment score and clinical assessment score is greater than 1
before ascending (Screening visit and Visit 1);

4. Blood oxygen saturation (SpO2) <95% at sea level;

5. Subjects with abnormal renal or liver function with clinical significance (ALT or AST
> 2×ULN, Cr > ULN);

6. Subjects with CRP > ULN;

7. Subjects with primary headache;

8. Surgery or blood donation within 3 months prior to screening;

9. On treatment of any medications (including any dietary supplements) except for birth
control within 14 days prior to screening and throughout the study period;

10. Contradictive to treatment of Danshen (Radix Saliva Miltiorrhiza Bge., RSM) products;

11. Women in pregnancy or lactation period;

12. Substance abuse. Subjects with a recent history (within the last 2 years) of
alcoholism or known drug dependence;

13. Participation in any other clinical trial on an investigational drug within 30 days
prior to screening;

14. A family member or relative of the study site staff;

15. Any other 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.