Clinical trial NCT06076681
Conditions: Helicobacter Pylori Infection
Sponsor: TenNor Therapeutics (Suzhou) Limited
Start date: 2021-09-27; Completion date: 2022-01-06
Enrollment: 40 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase Ⅰb/Ⅱa, single-center, randomized, open-label study was designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary Helicobacter Pylori eradication efficacy in asymptomatic subjects with Helicobacter Pylori infection after multiple doses of TNP-2198 capsules combined with rabeprazole sodium enteric-coated tablets, or TNP-2198 capsules combined with rabeprazole sodium enteric-coated tablets and amoxicillin capsules.

Detailed description:

Arms: arm 1: TNP2198 capsules 200 mg BID + rabeprazole sodium enteric-coated tablets 20 mg BID arm 2: TNP2198 capsules 400 mg BID + rabeprazole sodium enteric-coated tablets 20 mg BID arm 3: TNP2198 capsules 600 mg BID + rabeprazole sodium enteric-coated tablets 20 mg BID arm 4: TNP2198 capsules 400 mg BID + rabeprazole sodium enteric-coated tablets 20 mg BID + amoxicillin capsules 1g BID
Interventions: intervention 1: TNP-2198 intervention 2: Rabeprazole Sodium intervention 3: Amoxicillin
Intervention descriptions: intervention 1: On Days 1 to 14, all subjects in each group received TNP-2198 capsule within 30 minutes after breakfast and dinner (BID) for 14 consecutive days. On Day 15, the subjects were only administered once within 30 minutes after breakfast. intervention 2: On Days 1 to 14, all subjects in each group received rabeprazole within 30 minutes before breakfast and dinner (BID) for 14 consecutive days. On Day 15, the subjects were only administered once within 30 minutes before breakfast. intervention 3: On Days 1 to 14, all subjects in each group received Amoxicillin capsule within 30 minutes after breakfast and dinner (BID) for 14 consecutive days. On Day 15, the subjects were only administered once within 30 minutes after breakfast.

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 3 
 
 
A Single-center, Randomized, Open-label Phase Ib/IIa Clinical Study to Evaluate the Safety, 
Tolerability, Pharmacokinetics, and Preliminary Efficacy of Helicobacter Pylori Eradication 
after Multiple Doses of TNP-2198 Capsules Combined with Rabeprazole Sodium Enteric-
Coated Tablets, and Multiple Doses of TNP-2198 Capsules Combined with Rabeprazole 
Sodium Enteric-Coated Tablets and Amoxicillin Capsules in Asymptomatic Healthy 
Participants with Positive Helicobacter Pylori Infection 
 
 
Protocol Synopsis 
 
 
Protocol No.: TNP-2198-04 
 
 
Approval Date: 20 June 2021 
 
 
 


Page 2 of 3 
Protocol Synopsis 
Study Title 
A Single-center, Randomized, Open-label Phase Ib/IIa Clinical Study to Evaluate the 
Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Helicobacter Pylori 
Eradication after Multiple Doses of TNP-2198 Capsules Combined with Rabeprazole 
Sodium Enteric-Coated Tablets, and Multiple Doses of TNP-2198 Capsules Combined 
with Rabeprazole Sodium Enteric-Coated Tablets and Amoxicillin Capsules in 
Asymptomatic Healthy Participants with Positive Helicobacter Pylori Infection 
Study Objectives 
Primary Objectives: 
1 
To evaluate the safety and tolerability of multiple doses of TNP-2198 Capsules 
combined with Rabeprazole Sodium Enteric-coated Tablets, and multiple doses of 
TNP-2198 Capsules combined with Rabeprazole Sodium Enteric-coated Tablets and 
Amoxicillin Capsules in asymptomatic healthy participants with positive Helicobacter 
pylori infection; 
2 
To evaluate the pharmacokinetics of multiple doses of TNP-2198 (including major 
metabolites), rabeprazole, and amoxicillin in each treatment group. 
 
Secondary Objectives: 
To evaluate the preliminary efficacy of multiple-dose combination of TNP-2198 Capsules 
and Rabeprazole Sodium Enteric-coated Tablets and multiple-dose combination of TNP-
2198 Capsules, Rabeprazole Sodium Enteric-coated Tablets and Amoxicillin Capsules in 
the eradication of Helicobacter pylori. 
Clinical Study 
Protocol No. 
TNP-2198-04 
Sponsor 
TenNor Therapeutics 
Clinical Trial 
Notification No. 
CXHL1800160/161 
Study Facility 
Phase I Drug Clinical Study Center of the First Bethune Hospital of Jilin University 
Study Phase 
Phase Ib/IIa 
Investigational 
Products 
TNP-2198 Capsules 
     Manufacturer: WuXi STA (Shanghai) Co., Ltd. (entrusted) 
     Strength: 100 mg  
     Storage Condition: Preserve in tightly closed containers, protected from light and 
stored at ambient temperature (10-30 °C) 
 
Rabeprazole Sodium Enteric-coated Tablets 
     Manufacturer: Eisai China lnc. 
     Drug Approval No.: GuoYaoZhunZi H20090090 
     Strength: 20 mg 
     Storage Condition: Preserve in tightly closed containers, protected from light and 
stored below 25 °C 
 
Amoxicillin Capsules 
     Manufacturer: Zhuhai United Laboratories (Zhongshan) Co., Ltd. 
     Drug Approval No.: GuoYaoZhunZi H44021351 
     Strength: 0.25 g 
     Storage Condition: Below 25 °C 
Study Design 
Participants: 40 asymptomatic healthy participants positive for Helicobacter pylori 
infection, males and females. 


Page 3 of 3 
The study is designed to evaluate the safety, tolerability, and pharmacokinetics of multiple 
doses of TNP2198 Capsules combined with Rabeprazole Sodium Enteric-coated Tablets, 
and multiple doses of TNP-2198 Capsules combined with Rabeprazole Sodium Enteric-
coated Tablets and Amoxicillin Capsules in asymptomatic healthy participants with 
positive Helicobacter pylori infection, and to evaluate the preliminary efficacy of each 
dosage regimen for Helicobacter pylori eradication. 
A total of 4 treatment groups will be set up in this study and the participants will be 
randomized at a ratio of 1: 1: 1: 1. 
 
Group A: TNP-2198 Capsules 200 mg twice daily (BID) + Rabeprazole Sodium 
Enteric-coated Tablets 20 mg BID (n=10); 
 
Group B: TNP-2198 Capsules 400 mg BID + Rabeprazole Sodium Enteric-coated 
Tablets 20 mg BID (n=10); 
 
Group C: TNP-2198 Capsules 600 mg BID + Rabeprazole Sodium Enteric-coated 
Tablets 20 mg BID (n=10); 
 
Group D: TNP-2198 Capsules 400 mg BID + Rabeprazole Sodium Enteric-coated 
Tablets 20 mg BID + Amoxicillin Capsules 1 g BID (n=10). 
Screening will occur within 14 days of the first dose of study investigational products. All 
participants will provide informed consent and undergo Screening evaluations to 
determine their eligibility. Eligible participants will be admitted to the clinical study center 
on day -1 (the day before dosing, D-1). On Day 1 to Day 14, breakfast and dinner will be 
completed within 30 minutes prior to dosing, and the investigational products will be 
administered after meals. On Day 15, breakfast will be completed within 30 minutes prior 
to dosing, and the last dose will be administered after meals. Pharmacokinetic blood 
samples will be collected at the time points scheduled in the protocol during the study, and 
the safety tolerability evaluation and 14C urea breath test (UBT) will be conducted. 
All participants will be discharged after completion of the safety and tolerability 
evaluation on Day 17 and return to the clinical study center for a follow-up UBT test 
between Days 44 and 50 to evaluate the preliminary efficacy of Helicobacter pylori 
eradication. 
Screening 
Evaluations 
Participants will be screened from D-14 to D-2. 
Screening evaluations: demographic information (including sex, ethnicity, age, weight, 
height and BMI), medical history, surgical history, smoking history, reproductive status, 
drinking history/diet, prior medications, physical examination, vital signs (blood pressure, 
pulse rate, respiratory rate and body temperature), 12-lead ECG, chest plain X-ray, 
abdominal Dopler ultrasound (digestive system + urinary system), clinical laboratory tests 
(hematology, blood biochemistry, urinalysis and coagulation function), infectious disease 
tests (hepatitis B serologic test, hepatitis C antibody, hepatitis C core antigen, HIV 
antigen/antibody, treponema pallidum antibody [an additional rapid plasma regain (RPR) 
test is required in patients positive for treponema pallidum antibody), serum pregnancy 
test (females only ) and UBT. 
Note: The test results of hepatitis B virus, hepatitis C antibody, hepatitis C core antigen, 
HIV antigen/antibody and treponema pallidum antibody are valid within 3 months; Chest 
anteroposterior radiograph valid within 1 year; Abdominal Dopler ultrasound valid within 
1 month. 
Admission 
(Baseline) 
Evaluations 
Admission (baseline) will be occurred on D-1. 
Baseline evaluations: Medical history, surgical history, clinical laboratory tests, physical 
examination, vital signs, 12-lead ECG, serum pregnancy test (females only), urine drug 
screen (morphine, marijuana), alcohol breath test, UBT. 
Note: Screening results are valid within 7 days for clinical laboratory tests and UBT. 
Dosing Regimen 
The investigational products shall be orally administered twice daily after completion of 
meals, for 14 consecutive days. On Day 15, the participants have breakfast within 30 
minutes prior to dosing, and the last dose shall be taken after completion of meals. Each 
participant takes 29 doses of the investigational product. The dose of the investigational 
product for each group are as follows: 
 
Group A: TNP-2198 Capsules 200 mg/time, i.e. 2 capsules/time; Rabeprazole Sodium 
Enteric-coated Tablets, 20 mg/time, i.e., 1 tablet/time; 


Page 4 of 3 
 
Group B: TNP-2198 Capsules 400 mg/time, i.e., 4 capsules/time; Rabeprazole 
Sodium Enteric-coated Tablets, 20 mg/time, i.e., 1 tablet/time; 
 
Group C: TNP-2198 Capsule 600 mg/time, i.e. 6 capsules/time; Rabeprazole Sodium 
Enteric-coated Tablets, 20 mg/time, i.e., 1 tablet/time; 
 
Group D: TNP-2198 Capsules 400 mg/time, i.e., 4 capsules/time; Rabeprazole 
Sodium Enteric-coated Tablets, 20 mg/time, i.e., 1 tablet/time; Amoxicillin Capsules, 
1 g/time, i.e., 4 capsules/time. 
Inclusion Criteria 
Participants must meet all of the following criteria to be enrolled: 
1 
Have signed the informed consent form before the study, and fully understand the 
study contents, process and possible adverse reactions; 
2 
Participants who are able to complete the study as required by the protocol; 
3 
Participants are willing to have no pregnancy plan within 6 months after last dose of 
investigational products and voluntarily take effective contraceptive measures; 
4 
Male and female participants aged 18-65 years (inclusive); 
5 
Male participants weighing not less than 50 kg and female participants weighing not 
less than 45 kg; Body mass index within the range of 18-30 kg/m2 (inclusive); 
6 
Health status: participants do not have history of clinically significant cardiovascular, 
liver, kidney, digestive tract, nervous system, respiratory system, mental disorder and 
metabolic disorder; 
7 
Physical examination and vital signs are normal or abnormal but not clinically 
significant as judged by the investigator; 
8 
Paticipants whose 14C urea breath test (UBT) results are positive. 
9 
Clinical laboratory test results are within normal range or abnormal but not clinically 
significant as judged by the investigator. 
Exclusion 
Criteria 
Participants were not to be enrolled if they met any of the following exclusion criteria: 
1 
History of helicobacter pylori eradication therapy (including participation in other 
clinical studys for helicobacter pylori eradication); 
2 
Those who smoked more than 5 cigarettes per day in the 3 months prior to screening; 
3 
Those who are allergic to the investigational product or or its excipients, or 
participants with allergic constitution (multiple drug and food allergies); 
4 
Those who have a history of drug and/or alcohol abuse (average weekly consumption 
of ≥ 14 units of alcohol: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of 
wine); 
5 
Those who have blood donation or massive blood loss (> 450 mL) within 3 months 
prior to screening; 
6 
Those who have taken any drug that changes the activity of liver enzyme within 28 
days prior to screening; 
7 
Those who have taken any prescription drugs, over-the-counter drugs, any vitamin 
products, or herbal remedies within 14 days prior to screening; 
8 
Those who have taken special diet (including pitaya, mango, grapefruit, etc.) or have 
had strenuous exercise within 2 weeks prior to screening, or other factors affecting 
drug absorption, distribution, metabolism, excretion, etc.; 
9 
Those who have had a major change in diet or exercise habits recently; 
10 Those who have taken the other study drug or participated in the other clinical study 
that have not been finished within 1 month prior to administration of the 
investigational product; 
11 Those who have a history of dysphagia or any gastrointestinal disease affecting drug 
absorption; 
12 Those who have any disease that increases the risk of bleeding, such as hemorrhoids, 
acute gastritis or gastric and duodenal ulcers; 
13 Those who have abnormal ECG with clinical significance; 
14 Female participants who are in lactation or have a positive result in serum pregnancy 
test at screening or during the course of the study; 


Page 5 of 3 
15 Those with symptoms of cardiovascular, digestive, respiratory, urinary, neurological, 
hematological, immunological, endocrine system or tumor, and mental illness or with 
past medical history that has not been cured; 
16 The following diseases (including but not limited to gastrointestinal, renal, hepatic, 
neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric 
or cardiovascular and cerebrovascular diseases) with clinically significant 
abnormalities in clinical laboratory tests or other clinical findings; 
17 Viral hepatitis (including hepatitis B and C), HIV antibody, treponema pallidum 
antibody positive (those with positive treponema pallidum antibody need additional 
RPR test); 
18 Acute illness or concomitant medication from the time of signing the informed 
consent form to the time before administration of the investigational product; 
19 Consumption of chocolate, any caffeine-containing or xanthine-rich food or 
beverages within 48 hours prior to administration of the investigational product; 
20 Those who have taken any alcohol-containing products within 48 hours prior to 
administration of investigational product; 
21 Those with a positive result in urine drug screening or a history of drug abuse or drug 
use within the past 5 years; 
22 Other conditions considered unsuitable for participation in the study by the 
investigator. 
Safety and 
Tolerability 
Evaluation 
CTCAE 5.0 criteria are used.  
All participants are observed for any adverse events occurring during the clinical study, 
and their clinical manifestations, severity, onset time, end time, treatment measures and 
outcome are recorded, and their correlation with the investigational product shall be 
determined. 
Safety and tolerability evaluation includes adverse events (AE), clinical laboratory tests 
(hematology, blood biochemistry, coagulation, urinalysis), vital signs (blood pressure, 
pulse rate, respiratory rate and body temperature), 12-lead electrocardiogram (ECG) and 
physical examination. 
Pharmacokinetics 
Sample Collection 
and Processing 
Methods 
The test sample is plasma and the test substances are: TNP-2198 (including major 
metabolites), rabeprazole and amoxicillin. 
 
Collection time points: 
 
Day 1: within 30 minutes before breakfast, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 
10, 11, and 12 h after dosing (prior to the second dose of the day); 
 
Days 3, 5, 7, 9, 11, 13, and 14: within 30 min before breakfast; 
 
Day 15: within 30 minutes before breakfast and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 
9, 10, 11, 12, 24 (Day 16) and 48 (Day 17) h after dosing. 
Processing method: 
Whole blood is collected in vacuum blood collection tubes containing anticoagulant, 4 mL 
per tube, and plasma is obtained by centrifugation after completion of whole blood 
collection, and the plasma samples are divided into two aliquots and stored in a  
refrigerator at -80 °C, one for pharmacokinetics analysis and the other as a backup. The 
process from sample collection to the refrigerator at -80 °C storage needs to be completed 
within 1 hour. Refer to the Laboratory Operation Manual for specific operation 
requirements. 
PK Parameters 
First dose PK parameters include at least: 
 
Time to peak concentration (Tmax) 
 
Peak concentration (Cmax) 
 
Elimination half-life (t1/2) 
 
Area under the plasma concentration-time curve from the first dose extrapolated to 
infinity (AUC0-∞) 
 
Area under the plasma concentration-time curve from the first dose to the dosing 
interval (12 h) (AUC0-tau) 


Page 6 of 3 
 
Apparent volume of distribution (Vd/F) 
 
Apparent clearance (CL/F) 
 
Last dose PK parameters include at least: 
 
Time to peak (Tmax,ss) 
 
Maximum plasma concentration at steady state (Cmax,ss) 
 
Minimum plasma concentration at steady state (Cmin,ss) 
 
Mean plasma concentration at steady state（Cavg,ss) 
 
Elimination half-life (t1/2,ss) 
 
Area under the plasma concentration-time curve from the last dose to the last 
measurable concentration time point (AUC0-last, ss) 
 
Area under the plasma concentration-time curve from the last dose to the dosing 
interval (12 h) (AUC0-tau,ss) 
 
Area under the plasma concentration-time curve from the last dose extrapolated to 
infinity (AUC0-∞, ss) 
 
Apparent volume of distribution at steady state (V/Fss) 
 
Apparent clearance (CL/Fss) 
 
Accumulation Index (Rac): AUC0-tau,ss on Day 15/AUC0-tau on Day 1 
 
Fluctuation index (DF): Percentage fluctuation at steady state = 100 × (Cmax,ss - 
Cmin,ss)/Cavg, ss 
Preliminary 
Evaluation of 
Helicobacter 
pylori 
Eradication 
All participants will undergo a total of 4 UBT tests (under fasting conditions before 
breakfast) at baseline, Day 8, Day 16, and Day 44-50 after last dosing, to evaluate the 
preliminary efficacy in the eradication of Helicobacter pylori. 
Statistical 
Analysis 
Safety and tolerability analysis 
The analysis of safety and tolerability are mainly based on descriptive statistics. AEs, 
serious adverse events (SAEs), drug-related AEs and AEs leading to withdrawal from the 
study are summarized. 
The number of participants, number of AEs and incidence of all AEs will be tabulated and 
summarized by treatment group, system organ class and preferred term. 
The incidence of adverse events (occurring separately in each treatment group, both in 2 
groups, or in 3 groups) in each treatment group will be tabulated and described according 
to CTCAE grade by treatment group. 
The number of participants, number of AEs and incidence of AEs in each treatment group 
will be tabulated according to severity and relationship to the investigational product by 
system organ class and preferred term. 
The laboratory test results that are normal before the test but abnormal after treatment are 
described by treatment group. 
The mean, standard deviation, median, minimum and maximum values of vital signs 
(blood pressure, respiratory rate, pulse rate and body temperature) and laboratory test 
before and after administration are calculated according to the treatment group, 
respectively. If necessary, paired t test or non-parametric test can be used for comparison 
before and after administration. 
SAE and suspected unexpected serious adverse reactions (SUSARs) are presented 
separately. 
 
Pharmacokinetic parameter analysis 


Page 7 of 3 
Plasma concentrations will be summarized descriptively by treatment group and time 
point, including: arithmetic mean, standard deviation, minimum, median, maximum, 
geometric mean, coefficient of variation, geometric coefficient of variation. Descriptive 
analysis will be performed for the pharmacokinetic parameters calculated after the first 
and last administration by treatment group, including: arithmetic mean, standard deviation, 
minimum, median, maximum, geometric mean, coefficient of variation, geometric 
coefficient of variation, etc. In addition, the accumulation index AUC0-tau,ss (D15)/AUC0-tau 
(D1) is calculated. Mean and individual concentration-time curves are displayed by linear 
and semi-logarithmic plotting. Analysis of variance or non-parametric test will be 
performed on pharmacokinetic parameters between each treatment group. 
 
Preliminary analysis of Helicobacter pylori eradication 
The preliminary eradication effect analysis will be based on the full analysis set, which is 
defined as all participants who are randomized and receive at least one dose of 
investigational product. The preliminary efficacy of Helicobacter pylori eradication will be 
analyzed descriptively by frequency (percentage) of 4 UBT test results (negative or 
positive) at baseline, on Day 8, Day 16 and Day 44-50 after last dosing in different 
treatment groups, and inter-group comparison will be performed. Fisher's exact test will be 
used for inter-group comparison. As an auxiliary analysis, the mean, standard deviation, 
median, minimum, maximum, and change from baseline will be presented for UBT 
values. Inter-group comparisons of UBT values will be analyzed using the model of 
analysis of covariance or mixed-effects model repeated-measures (MMRM) with baseline 
UBT values as a covariate, treatment group and dose group as a fixed variable. If the 
model of analysis of covariance was used, the last observation carried forward (LOCF) 
was used to impute missing values. 
There are no clear statistical hypotheses in this study and all statistical tests are 
exploratory test with a two-sided 5% nominal significance level. The statistical analysis 
method and plan are detailed in the statistical analysis plan. 
 


Protocol No.: TNP-2198-04 
Version No.: 1.1 Version Date: June 20, 2021 
Page 8 of 3 
Schedule of Activities 
Study Procedures 
Screening Visit 
(D-14-D-2) 
D-1 
D1 
D2-14 
D15 
D16 
D17 
Follow-up (during D44-
50) 
Screening 
Signing of ICF 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical and surgical history 
X 
X 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
Chest plain X-ray 
X 
 
 
 
 
 
 
 
Abdominal Doppler ultrasound 
(digestive system + urinary 
system) 
X 
 
 
 
 
 
 
 
Infectious disease screening 
(hepatitis B serologic test, 
hepatitis C core antigen, hepatitis 
C antibody, HIV 
antigen/antibody, treponema 
pallidum antibody) 
X 
 
 
 
 
 
 
 
Breath alcohol test 
  
X 
  
  
  
  
  
  
Urine drug screening (morphine, 
marijuana) 
  
X 
  
  
  
  
  
  
Blood pregnancy test 
X 
X 
  
  
  
  
X 
  
Verification of inclusion and 
exclusion criteria 
X 
X 
  
  
  
  
  
  
Enrollment 
Admission 
  
X 
  
  
  
  
  
  
Randomization 
  
 X 
  
  
  
  
  
  
Study treatment 
administration 
Dosing 
  
 
X 
X 
X 
  
  
  
Clinical laboratory tests (blood 
routine, blood biochemistry, 
coagulation, urine routine)1 
X 
X 
  
X 
  
  
X 
  


Protocol No.: TNP-2198-04 
Version No.: 1.1 Version Date: June 20, 2021 
Page 9 of 3 
Safety and 
tolerability 
Assessment 
Physical examination2 
X 
X 
  
X 
  
  
X 
  
12-lead ECG3 
X 
X 
X 
  
X 
 
X 
  
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
  
Monitoring and recording of 
adverse events 
 
 
X 
X 
X 
X 
X 
X 
PK sample 
collection 
Blood sample5 
  
  
X 
X 
X 
X 
X 
  
Preliminary efficacy 
of Hp eradication 
14C-urea breath test6 
X 
 X 
  
X 
  
X 
  
X 
End of study 
Discharge 
  
  
  
  
  
  
X 
  
Follow-up, study completion 
  
  
  
  
  
  
  
X 
Note: 
1 
Clinical laboratory tests will be performed at the screening period, baseline period, D4, D6, D8, D12 (before the first dose), and D17 (48 h after dosing on D15). The 
results of screening examination within 7 days can be used for the baseline period, and no additional test will be required. 
2 
Physical examination will be performed at the screening period, baseline period (D-1), D4, D6, D8, D12 and D17. 
3 
12-lead ECG will be performed at the screening period, baseline period (D-1), D1 (2 h after the first dose), D15 (within 60 min before and 2 h after dosing) and D17 (48 
h after dosing on D15). 
4 
Vital signs will be examined at the screening period, baseline period (D-1), D1 (within 60 min before the first dose and 0.5 h, 2 h, 4 h, 8 h, 12 h after dosing), D2-14 
(within 60 min before the first dose), D15 (within 60 min before dosing and 0.5 h, 2 h, 4 h, 8 h, 12 h after dosing), D16 (24 h after dosing on D15) and D17 (48 h after 
dosing on D15). 
5 
PK blood samples will be collected on D1 (within 30 min before breakfast, and 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 5 h, 6 h, 7 h, 8 h, 9 h, 10 h, 11 h, 12 h after 
dosing), within 30 min before breakfast on D3, D5, D7, D9, D11, D13 and D14, on D15 (within 30 min before breakfast, and 0.5 h, 1 h, 1.5 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 5 
h, 6 h, 7 h, 8 h, 9 h, 10 h, 11 h, 12 h after dosing), D16 (24 h after dosing on D15) and D17 (48 h after dosing on D15). 
6 
UBT will be performed in fasting state before breakfast and will be performed on D8 during D2-14; the results of screening examination within 7 days can be used for 
the baseline period, and no additional test will be required