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

Acute Mountain Sickness Clinical Trial

— T89-AMS  

Official title:

A Double-blind, Randomized and Placebo-controlled Phase 2 Study to Evaluate the Safety and Efficacy of T89 in Prevention and Treatment of Acute Mountain Sickness (AMS) During Rapid Ascent

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03621410
• Other study ID #: T89-30-AMS
• Secondary ID: UCSF IRB 17-2395
• Status: Recruiting
• Phase: Phase 2
• Start date: June 1, 2018
• Est. completion date: October 2019

Study information

• Verified date: September 2019
• Source: University of California, San Francisco
• Contact: Koa Gudelunas
• Phone: 4154768984
• Email: dantonic_ams_trial[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the safety and efficacy of T89 in preventing Acute Mountain Sickness (AMS) and relieving the symptoms of AMS during rapid ascent.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: October 2019
• Est. primary completion date: October 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Mountain Sickness
• Altitude Sickness

Intervention

Drug:
• T89 225 mg group
The study drug will be given orally for 14 days (Days 1-14) as pre-treatment before ascending, followed by a 5-day high-altitude treatment and observation period (Days 15-19).
• Placebo
Placebo group
• T89 300 mg group
For the pre-treatment period in the T89 300 mg group, subjects will take placebo on Days 1-12, and take T89 (300 mg, BID) on Days 13-19.

Locations

Country	Name	City	State
United States	UCSF	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Tasly Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Placebo group vs treatment group LLSS scores	The self reported and clinical assessment of Lake Louise Scores will be compared between the placebo group and the T89 treatment group. The Lake Louise Scoring System (LLSS) is used to diagnose Acute Mountain sickness (AMS). The self reported LLSS asks a sojourner to altitude whether or not they have any of the hallmark signs of AMS and to rate the severity on a scale of 0-3, 0 being no symptoms and 3 being severe. These hallmark signs include Headache, Gastrointestinal symptoms, Fatigue and weakness, Dizziness and lightheadedness, and Difficulty sleeping. A Lake Louise score of 3-5 signifies mild AMS and >6 signifies severe AMS. The clinical assessment of the Lake Louise score includes checking sojourners for Ataxia, Edema and changes in mental status. These are also rated on a scale from 0 to 3 with 0 being asymptomatic and 3 being severe.	Over 3 weeks while subject is a participant in the study. Twice at sea level and 10 times at altitude