Evaluate the Efficacy of RespireAidTM in Patient With Externally Contracted Seasonal Epidemic (外感時疫)
Phase: NA
Conditions: Respiration Disorders
Sponsor: Sun Ten Pharmaceutical Co., Ltd.

Protocol number：MOHW-112-CM3B-01    CONFIDENTIAL                    Version 1.1/Date: 2023-06-27 
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Protocol Synopsis 
 
I. 
Protocol title: 
Evaluate the efficacy of RespireAidTM in patient with externally contracted seasonal epidemic  
II. 
Objectives: 
The main objective of this study is to evaluate the clinical efficacy of the RespireAidTM (Tai-wan-
Qing-Guan-Yi-Hao) to ease the symptoms of fever, sore throat, and cough, and the safety after 
treatment. 
III. Test drug 
1. Name: RespireAidTM (Tai-wan-Qing-Guan-Yi-Hao) (NRICM101) 
2. Dosage form: oral granule 
3. Strength: 5g/sachet 
4. Packing type: sachet 
5. Dosage and administration: 
Take 1 sachet(5g) 4 times daily  
6. Mechanism of action (if known): 
RespireAidTM have three targeting potential pathways in externally contracted seasonal 
epidemic: binding of viral spike protein to human angiotensin-converting enzyme 2 (ACE2), 
3CL protease that facilitates virus replication, production of pro-inflammatory cytokines 
interleukin (IL)-6 and tumor necrosis factor (TNF)-α. 
IV. Developmental phase: □First in human Phase □Ⅰ □Ⅱ ■Ⅲ □Ⅳ  
V. Study design: 
1. ■Control: ■placebo 
□active (please specify name and dosage) 
□other 
□Uncontrolled 
2. Blinding: □open label □evaluator blind □ single blind ■ double blind 
□double dummy □other 
3. Randomized: ■yes □no 
4. ■Parallel □Cross over □Other 
5. Duration of treatment: 5 days 
6. Titration: □forced □optional ■none 
7. □Single national ■Multi center(Taiwan) □Multi center 
VI. Endpoints 
1. Primary endpoint(s): 
Efficacy endpoint 
 
Time to symptom-free for fever. 

Protocol number：MOHW-112-CM3B-01    CONFIDENTIAL                    Version 1.1/Date: 2023-06-27 
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Safety endpoint 
 
Treatment-emergent adverse events (TEAEs) 
2. Secondary endpoints: 
Efficacy endpoint 
 
Time to symptom-free for sore throat. 
 
The change from baseline in the severity of cough during treatment period. 
Safety endpoint 
 
Physical examination 
 
Vital sign 
VII. Selection criteria 
1. Main inclusion criteria: 
(1) Male or unpregnant female patients ≥ 18 years to ≤ 79 years of age, who have the 
symptoms of fever, sore throat, and cough (match the definition in table 1 to 2 in 
protocol), by investigator’s judgement, with mild to severe symptoms (> 20 mm in 
each VAS). 
(2) With BMI between 18 to 30 kg/m². 
(3) Without a history for alcohol or drug abuse, or other significant organic diseases. 
(4) No history of cancer. Unless no signs of relapse occurred for over 5 years which no 
anticancer therapies are needed. 
(5) Ability to read and write Chinese, and provide data through questionnaire. 
(6) Ability to understand and comply all procedures of the study, and provide written 
consent.  
2. Main exclusion criteria: 
(1) Confirmed diagnosis of pneumonia or other disease by chest X ray which would 
impact on study evaluations. 
(2) Must require long-term use of NASIDs, corticosteroids or other immunosuppressive 
agents. 
(3) Pregnant female. 
(4) Subjects are not suitable for the conduct of the study for any other reasons, determined 
by the investigator. For example, subjects who require to use antibiotics, COVID-19 
or influenza antiviral drugs. 
VIII. Study procedures: 
This is a multicenter, parallel, double-blind, randomized, placebo-controlled study. A total of 258 
male or unpregnant female outpatient subjects ≥ 18 years to ≤ 79 years of age will be enrolled into 
this study (dropout rate 10%). There will be 2 visits in this study. In Visit 1 (Day 1), subjects who 
have the symptoms of fever, sore throat, and cough (match the definition in table 1 to 3 in protocol), 
by investigator’s judgement will be recruited into the study. 
Subjects will be randomized into the RespireAidTM group or placebo group with allocation rate 2:1. 

Protocol number：MOHW-112-CM3B-01    CONFIDENTIAL                    Version 1.1/Date: 2023-06-27 
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Following to the clinical guideline of NRICM101, subjects in RespireAidTM group will take drug 
four times daily with 20g oral granule, administered for 5 days. The subjects in placebo group 
received study drug with the same dose frequency. Other than study drugs, the rescue drug, 
acetaminophen, will be administered. If subjects have moderate or severe fever, sore throat, he/she 
could receive one rescue medication (500mg) per 4 hours, up to 6 tablets in total in one day. 
Subjects will be educated how to use e-dairy. The dairy will be recorded the severity of fever, sore 
throat, and cough from baseline (Day 1, before use of study drug) to Day 5. The efficacy endpoint 
will be the improvement of fever, sore throat, and cough, and the safety endpoint will be adverse 
events after treatment. The study and rescue drugs will be dispensed to subjects and the study staff 
will teach them how to receive medications. If subjects have persistent fever, unscheduled visits 
will be arranged to check whether or not they would be suitable to participate into this study. 
Adverse events will be recorded at Visit 2(Day 8), and the dairy with drug record will be checked. 
IX. Concomitant treatment: 
1. During study period, the drugs which may impact the efficacy evaluation (i.e. fever, sore throat, 
and cough) will be prohibited, including 
(1) Chinese medication other than study drug 
(2) Western medication other than study drug 
 
NSAIDs 
 
Acetaminophen 
(3) Expectorant cough medicines 
 
Mucolytics, such as Bromhexine 
 
Antitussives, including Opioids (e.g. Codeine, Ethylmorphine, Pholcodine), 
nonopioids (e.g. Noscapine, Dextromethorphan, Chlophedianol), antihistaminics 
and Prenoxdiazine 
 
Adjuvant antitussives, such as bronchodilators 
2. During study period, long-term use of NASIDs, corticosteroids or other immunosuppressive 
agents will be prohibited. 
3. During study period, antibiotics, COVID-19 or influenza antiviral drugs will be prohibited. 
4. During study period, subject could receive other treatments/therapies that are not otherwise 
prohibited and, in the judgment of the Investigator, are required for proper medical care. 

Protocol number：MOHW-112-CM3B-01    CONFIDENTIAL                    Version 1.1/Date: 2023-06-27 
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X. Statistics 
1. Primary hypothesis: ■superiority   □non inferiority 
□equivalence  □other 
2. Sample size: enrolled 258 subjects 
evaluable 231 subjects 
3. Efficacy population: ■ITT ■PP □other 
Safety population:   □ITT □PP ■other: Safety Population 
4. Statistical method(s) for efficacy/safety evaluations: 
Efficacy Evaluation 
The primary efficacy endpoint is the “time to symptom-free for fever” which is the days of the 
symptom-free for fever based on the diary record. The primary endpoint will be analyzed by 
weighted log-rank test for comparison between RespireAidTM and placebo groups. Kaplan-
Meier plot will be drew to present the time to event data. The secondary efficacy endpoint of 
the “time to symptom-free for sore throat” will be analyzed as the analysis of the primary 
efficacy endpoint. The change from baseline in the severity of cough during treatment period 
will be summarized as categorical data with frequency and percentage and analyzed by Chi-
square test. 
Safety Evaluation 
All safety assessments, including AEs, physical examinations (PEs), and vital signs (VS), 
where indicated, will be presented using descriptive statistics by study groups and time points. 
5. Planned interim analysis: □yes ■no 
 
XI. Please attach flow chart and/or assessment schedule, if available. 
Visit 
1 
2 
 
Screening/Strat of 
Treatment 
End of Treatment/End of 
Study/Early withdrawal 
Days 
1 
8 
Windows 
 
 
Informed Consent 
X 
 
Inclusion/Exclusion criteria 
X 
 
Randomization 
X 
 
Medical History 
X 
 
Demographic data 
X 
 
Physical Examination 
X 
X 
Vital Signs 
X 
X 
COVID-19 testing 
 
 
ChestＸray 
X 
 
Urine Pregnancy test a 
X 
 
Dispense study drug b 
X 
 

Protocol number：MOHW-112-CM3B-01    CONFIDENTIAL                    Version 1.1/Date: 2023-06-27 
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Dispense rescue drug c 
X 
 
Return study drug 
 
X 
Return rescue drug 
 
X 
e-diary d 
X 
X 
Concomitant Medication 
X 
X 
TEAE 
X 
X 
a: If the result of urine pregnancy test is positive, the subject won’t be enrolled into the study. 
b: The study drugs will be given four times daily with 20g oral granule, administered for 5 days.  
c: The rescue drugs could be given one tablet (500mg) per 4 hours, up to 6 tablets in total in one day. 
d: E-Dairy card will be recorded before use of study drugs(baseline), Day 1 to Day 5.