Clinical trial NCT06076694
Conditions: Helicobacter Pylori Infection
Sponsor: TenNor Therapeutics (Suzhou) Limited
Start date: 2022-06-26; Completion date: 2022-09-20
Enrollment: 80 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a single-center, randomized, open-label phase Ic/IIb clinical study to evaluate the efficacy and safety of TNP-2198 capsules, rabeprazole sodium enteric-coated tablets and amoxicillin capsules combined with multiple doses of rabeprazole sodium enteric-coated tablets and amoxicillin capsules compared with multiple doses of rabeprazole sodium enteric-coated tablets and amoxicillin capsules combined with multiple doses in Helicobacter pylori infection-positive population.

Detailed description:

Arms: arm 1: TNP-2198 capsules 400 mg + rabeprazole sodium enteric-coated tablets 20 mg + amoxicillin capsules 1 g; Twice daily (BID) for 14 days arm 2: TNP-2198 capsules 600 mg + rabeprazole sodium enteric-coated tablets 20 mg + amoxicillin capsules 1 g; BID for 14 days arm 3: TNP-2198 capsule 600 mg + rabeprazole sodium enteric-coated tablets 20 mg; Three times daily (TID) for 14 days arm 4: TNP-2198 capsules 600 mg + rabeprazole sodium enteric-coated tablets 20 mg + amoxicillin capsules 1g; TID for 7 days arm 5: Rabeprazole sodium enteric-coated tablets 20 mg + amoxicillin capsules 1 g
Interventions: intervention 1: TNP-2198 intervention 2: Rabeprazole Sodium intervention 3: Amoxicillin
Intervention descriptions: intervention 1: Group A, TNP-2198 capsules 400mg(4 capsules),BID, 14days Group B, TNP-2198 capsules 600mg(6 capsules),BID, 14days Group C , TNP-2198 capsules 600mg(6 capsules),TID, 14days Group D, TNP-2198 capsules 600mg(6 capsules),TID, 7days intervention 2: Group A,Group B,Control group: Rabeprazole sodium enteric-coated tablets 20 mg, BID, 14days Group C :Rabeprazole sodium enteric-coated tablets 20 mg, TID, 14 days Group D : Rabeprazole sodium enteric-coated tablets 20 mg, TID, 7 days intervention 3: Group A,Group B,Control group: Amoxicillin capsules 1g, BID, 14days Group D : Amoxicillin capsules 1g, TID, 7 days

Protocol documents:
Prot_SAP_000.pdf: 
Protocol No.TNP-2198-06 
Page 1 of 17 
 
 
 
A Single-center, Randomized, Open-label Phase Ic/IIb Clinical Study to Evaluate the Efficacy 
and Safety of Multiple Doses of TNP-2198 Capsules + Rabeprazole Sodium Enteric-coated 
Tablets + Amoxicillin Capsules, Multiple Doses of TNP-2198 Capsules + Rabeprazole Sodium 
Enteric-coated Tablets Compared with Multiple Doses of Rabeprazole Sodium Enteric-Coated 
Tablets + Amoxicillin Capsules in Participants with Positive Helicobacter Pylori Infection 
 
 
Protocol Synopsis 
 
 
Protocol No.: TNP-2198-06 
 
 
Approval Date; 20 January 2022 
 
 
 
 
 
 


Protocol No.TNP-2198-06 
Page 2 of 17 
Protocol Synopsis 
Study Title 
A Single-center, Randomized, Open-label Phase Ic/IIb Clinical Study to Evaluate 
the Efficacy and Safety of Multiple Doses of TNP-2198 Capsules + Rabeprazole 
Sodium Enteric-coated Tablets + Amoxicillin Capsules, Multiple Doses of TNP-
2198 Capsules + Rabeprazole Sodium Enteric-coated Tablets Compared with 
Multiple Doses of Rabeprazole Sodium Enteric-Coated Tablets + Amoxicillin 
Capsules in Participants with Positive Helicobacter Pylori Infection 
Study Objectives 
Primary Objectives: 
1 
To evaluate the helicobacter pylori eradication effect of multiple doses of 
TNP-2198 capsules, rabeprazole sodium enteric-coated tablets and amoxicillin 
capsules in participants with positive H. pylori infection; 
2 
To evaluate the helicobacter pylori eradication effect of multiple doses of 
TNP-2198 capsules and rabeprazole sodium enteric-coated tablets in 
participants with positive H. pylori infection. 
 
Secondary Objectives: 
1 
To evaluate the safety and tolerability of multiple doses of TNP-2198 capsules, 
rabeprazole sodium enteric-coated tablets, and amoxicillin capsules in 
participant with positive H. pylori infection; 
2 
To evaluate the safety and tolerability of multiple doses of TNP-2198 capsules 
and rabeprazole sodium enteric-coated tablets in participant with positive H. 
pylori infection; 
3 
To evaluate the pharmacokinetic characteristics of TNP-2198 (including major 
metabolites), rabeprazole, and amoxicillin. 
Study Endpoints 
Primary Study Endpoint 
H. pylori eradication rate (confirmed by 14C UBT) on Days 28 to 34 after the last 
dose. 
 
Secondary Study Endpoints 
1 
The negative rate of 14C UBT on Day 8 after the first dose; 
2 
The negative rate of 14C UBT on Day 16 after the first dose; 
3 
Safety endpoints: Incidence of adverse events (AE) during the study, 
correlation with the investigational medicinal product and severity, laboratory 
tests, vital signs, ECG, physical examination, etc.; 
4 
Pharmacokinetic endpoints: Pharmacokinetic parameters of TNP-2198, 
rabeprazole, amoxicillin in each group of consecutive administrations. 
Protocol No. 
TNP-2198-PO-06 
Sponsor 
TenNor Therapeutics 
Clinical Trial 
Notification No. 
CXHL1800160/161 
Study Facility 
Phase I Drug Clinical Study Center of the First Hospital of Jilin University, 
Department of Gastroenterology of the First Hospital of Jilin University 
Study Phase 
Phase Ic/IIb 


Protocol No.TNP-2198-06 
Page 3 of 17 
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: 0.5 g 
 
Storage conditions: to be determined 
Study Design 
Study participant: 80 participants positive for H. pylori infection. 
The purpose is to evaluate the efficacy, safety and tolerability, and pharmacokinetic 
characteristics of multiple-dose treatment with TNP-2198 capsules, rabeprazole 
sodium enteric-coated tablets and amoxicillin capsules, and TNP-2198 capsules 
and rabeprazole sodium enteric-coated tablets compared with continuous 
administration of rabeprazole sodium enteric-coated tablets and amoxicillin 
capsules. 
In this study, a total of 4 test groups and 1 control group are set, 80 participants are 
planned to be enrolled and randomly assigned in a ratio of 2:2:1:1:2: 
 
Study 
grouping 
Dosing regimen 
Frequency of 
administration 
and course of 
treatment 
  
Number of 
participants 
Test 
group 
Group 
A 
TNP-2198 capsules 400 mg, rabeprazole sodium 
enteric-coated tablets 20 mg, amoxicillin capsules 1 g 
BID × 14 
days 
20 
Group 
B 
TNP-2198 capsules 600 mg, rabeprazole sodium 
enteric-coated tablets 20 mg, amoxicillin capsules 1 g 
BID × 14 
days 
20 
Group 
C 
TNP-2198 capsules 600 mg, rabeprazole sodium 
enteric-coated tablets 20 mg 
TID × 14 
days 
10 
Group 
D 
TNP-2198 capsules 600 mg, rabeprazole sodium 
enteric-coated tablets 20 mg, amoxicillin capsules 1 g 
TID × 7 days 
10 
Control 
group 
Rabeprazole sodium enteric-coated tablets 20 mg, 
amoxicillin capsules 1 g 
BID × 14 
days 
20 
 
Eligible participants will be admitted to the clinical study center 1 day before 
dosing (D-1). 
 
Study procedures of Group A, Group B, Group C and Control Group 
(administration for 14 consecutive days): 


Protocol No.TNP-2198-06 
Page 4 of 17 
The participants take the investigational product every day on Days 1 to 14 (D1-
D14) aand take the last dose of the investigational product in the morning of Day 
15 (D15) according to the dosage regimen of each group. Pharmacokinetic blood 
samples will be collected at the time points scheduled in the protocol during the 
study, and safety and tolerability evaluation, and 14C UBT will be conducted. All 
participants are discharged from the study center after safety and tolerability 
evaluation and PK blood collection are completed on Day 17 (D17), and return to 
the study center for follow-up visit on Days 44 to 50 (D44-D50). Adverse events 
and laboratory test abnormalities are followed until complete response or return to 
baseline or steady state, safety and tolerability assessments are performed, and 14C 
UBT is performed to evaluate the effect of Hp eradication. 
 
Study procedures of Group D (administration for 7 consecutive days): 
The investigational product is administered daily on study Days 1 to 7 (D1-D7), 
and the last dose of the investigational product is administered as specified in the 
dosage regimen in the morning of Day 8 (D8). Pharmacokinetic blood samples will 
be collected at the time points scheduled in the protocol during the study, and 
safety and tolerability evaluation, and 14C UBT will be conducted. All participants 
are discharged from the study center after safety and tolerability evaluation and PK 
blood collection are completed on Day 10 (D10), and return to the study center for 
follow-up visit on Days 37 to 43 (D37-D43). Adverse events and laboratory test 
abnormalities are followed until complete response or return to baseline or steady 
state, safety and tolerability assessments are performed, and 14C UBT is performed 
to evaluate the effect of Hp eradication. 
Screening 
Examination Items 
and Time 
I.e., D-14-D-2. After the participants sign the informed consent form, collect and 
record their demographic information (including sex, ethnicity, age, weight, height, 
and calculate BMI), medical history, operation history, smoking history, 
reproductive status, alcohol history/diet, prior medication, etc. And conduct 
physical examination, record of vital signs (blood pressure, pulse rate, respiratory 
rate and body temperature), clinical laboratory tests (blood routine, blood 
biochemistry, urine routine and coagulation function), infectious disease screening 
(hepatitis B two half and half, hepatitis C antibody, HIV antigen/antibody, 
treponema pallidum antibody [rapid plasma reagin RPR test is required for those 
with positive treponema pallidum antibody]), serum pregnancy test (only for 
female participants), 12-lead electrocardiogram, chest plain X-ray, abdominal 
Dopler ultrasound (digestive system + urinary system) and 14C UBT. 
Note: Test results of hepatitis B two half and half, hepatitis C antibody, HIV 
antigen/antibody and treponema pallidum antibody are acceptable within 3 months 
before screening; The test results of chest plain X-ray are acceptable within 1 year 
before screening; The test results of abdominal Dopler ultrasound are acceptable 
within 1 month prior to screening. 
Admission (Baseline) 
Examination Items 
and Time 
I.e., D-1. Participants will be admitted to the clinical study center one day before 
dosing, medical and surgical history will be collected, physical examination will be 
performed, vital signs will be recorded, and the following tests will be performed: 
blood routine, urine routine, blood biochemistry, coagulation function, serum 
pregnancy test (only for female participants), urine drug screen (morphine, 
marijuana), alcohol breath test, ECG, and 14C UBT. Laboratory tests, except serum 
pregnancy test, are conducted within 7 days of baseline. The inclusion and 
exclusion criteria are checked again. Randomization numbers are assigned to 
enrolled participants. 
Hospitalization/Dosing 
Period 
1) Group A, Group B, Group C and Control Group 


Protocol No.TNP-2198-06 
Page 5 of 17 
The hospitalization/administration period is from D1 to D17. According to the 
dosage regimen, the investigational product is orally administered on time every 
day for 14 consecutive days, and the last dose of the investigational product is 
administered in the morning of D15. Physical examination, vital signs, blood 
routine, urine routine, blood biochemistry, coagulation function, ECG, 14C UBT 
and other tests will be performed during hospitalization, and PK blood samples will 
be collected at the time points specified in the protocol. After all tests (serum 
pregnancy test is required only for female participants) and PK blood collection are 
completed on D17, the participants can be discharged from the study center. 
 
2) Group D 
The hospitalization/administration period is from D1 to D10. According to the 
dosage regimen, the investigational product is orally administered on time every 
day for 7 consecutive days, and the last dose of investigational product is 
administered in the morning of D8. Physical examination, vital signs, blood 
routine, urine routine, blood biochemistry, coagulation function, ECG, 14C UBT 
and other tests will be performed during hospitalization, and PK blood samples will 
be collected at the time points specified in the protocol. Participants can be 
discharged from the study center on D10 after completion of all tests (serum 
pregnancy test for female participants only) and PK blood sampling. 
Follow-up Period 
Participants in Group A, Group B, Group C and Control Group will return to the 
study center for follow-up visit from D44 to D50. Participants in Group D will 
return to the study center for follow-up visit from D37 to D43. Adverse events and 
laboratory test abnormalities are followed until complete response or return to 
baseline or steady state, safety and tolerability assessments are performed, and 14C 
UBT is performed to evaluate the effect of Hp eradication. 
Dosing Regimen 
Group A, Group B and Control Group: 
Two doses per day, breakfast and dinner should be eaten within 30 minutes prior to 
dosing, and oral administration should be given after meals. All investigational 
products should be taken after meals for 14 consecutive days. On Day 15, 
participants will have breakfast within 30 minutes prior to dosing, and the last dose 
will be taken after completion of meals. Each participant will take 29 doses of 
investigational products. 
 
Group C, Group D: 
Three doses per day, 8 hours apart. Group C is administered for 14 consecutive 
days, with the last dose on the morning of Day 15, and each participant receives 43 
doses of investigational product; Group D is administered for 7 consecutive days, 
with the last dose on the morning of Day 8, and each participant receives 22 doses 
of investigational product. 
The drug name, dose and course of treatment in each group are shown in the 
following table: 
Study grouping 
Frequency of 
administration  
Number of capsules/tablets per dose 
Dosing 
course 
(days) 
TNP-2198 
capsules 
(100 
mg/capsule) 
Rabeprazole Sodium 
Enteric-coated Tablets 
(20 mg/tablet) 
Amoxicillin 
Capsules 
(0.5 g/capsule) 
Test 
group 
Group 
A 
BID 
4 
1 
2 
14 
Group 
B 
BID 
6 
1 
2 
14 
Group 
C 
TID 
6 
1 
- 
14 
Group 
D 
TID 
6 
1 
2 
7 
Control group 
BID 
- 
1 
2 
14 


Protocol No.TNP-2198-06 
Page 6 of 17 
Inclusion Criteria 
Participants must meet all of the following criteria to be enrolled: 
1 
Voluntary signing of the Informed Consent Form (ICF); 
2 
Age 18-65 years (inclusive), male or female; 
3 
Health status: participants do not have history of clinically significant 
cardiovascular, liver, kidney, digestive tract, nervous system, respiratory 
system, mental disorder and metabolic disorder; 
4 
Physical examination and vital signs are normal or abnormal but not clinically 
significant as judged by the investigator; 
5 
Clinical laboratory test results are within normal range or abnormal but not 
clinically significant as judged by the investigator; 
6 
Those whose 14C urea breath test (14C UBT) results are positive. 
7 
Participants must agree to have no pregnancy plan and voluntarily take 
effective contraceptive measures during the study and for at least 6 months 
after last dose administration; 
8 
Willing to follow and be able to complete all study procedures. 
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 products; 
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; 
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; 


Protocol No.TNP-2198-06 
Page 7 of 17 
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 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 the 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 by the investigator unsuitable for participation in 
the study. 
Safety and Tolerability 
Judgement Criteria 
CTCAE 5.0 criteria are used.  
Safety and Tolerability 
Evaluation  
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 mainly includes adverse events (AE), physical 
examination, vital signs (blood pressure, pulse rate, respiratory rate and body 
temperature), clinical laboratory tests (hematology, urinalysis, blood biochemistry, 
coagulation function) and ECG. 
Concomitant 
Medications 
All non-investigational products taken by the participant from the time of signing 
the informed consent form through the last study visit are considered concomitant 
medications, and information regarding the medication will be recorded on the 
CRF, including the drug name (trade name and generic name), start date, dose, 
mode of administration, reason for use, and stop date. 
Use of concomitant medications should be minimized during the study. However, 
if these medications are beneficial to the participant and necessary, and are not 
likely to interfere with the study, they may be administered at the discretion of the 
investigator. 
Prohibited 
Medications 
Any prescribed drugs or over-the-counter drugs, including vitamins, minerals, 
nutritional supplements, herbal remedies, etc., are not allowed within 2 weeks prior 
to screening and during the study, except for drugs used to treat adverse events. 
Pharmacokinetics 
Sample Collection  
PK collection time points: 
PK blood samples will be collected at the following time points. 
 
1) Blood sampling time points in Group A, Group B and Control Group: 
 
Day 1: within 30 Minutes Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 
10, 11, 12 Hours Post-Dose (Prior to the Second Dose of the Day); 
 
Days 3, 5, 7, 9, 11, 13, and 14: within 30 minutes prior to dosing; 
 
Day 15: Within 30 Minutes Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 
10, 11, 12, 24 Hours (Day 16) and 48 Hours (Day 17) Post-dose. 
 
2) Blood sampling time points in Group C: 
 
Day 1: within 30 minutes before dosing, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8 
hours after dosing (prior to the second dose of the day); 
 
Days 3, 5, 7, 9, 11, 13, 14: within 30 minutes prior to dosing; 


Protocol No.TNP-2198-06 
Page 8 of 17 
 
Day 15: Within 30 Minutes Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 
10, 11, 12, 24 Hours (Day 16) and 48 Hours (Day 17) Post-dose. 
 
3) Blood sampling time points in Group D: 
 
Day 1: within 30 minutes before dosing, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8 
hours after dosing (prior to the second dose of the day); 
 
Days 3, 5, 7: within 30 minutes prior to dosing; 
 
Day 8: Within 30 Minutes Pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 
10, 11, 12, 24 Hours (Day 9) and 48 Hours (Day 10) Post-dose. 
 
PK blood sample processing method: 
Whole blood is collected in vacutainers 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 -
80 ℃ refrigerator, one for pharmacokinetics analysis and the other as a backup.  
The process from sample collection to -80 ℃ refrigerator storage needs to be 
completed within 1 hour. Refer to the Laboratory Operation Manual for specific 
operation requirements. 
Pharmacokinetic 
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 (AUC0-tau) 
◼ 
Groups A, B, Control: dosing interval is 12 hours  
◼ 
Groups C, D: dosing interval is 8 hours  
 
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 (AUC0-tau,ss) 
◼ 
Groups A, B, Control: dosing interval is 12 hours  
◼ 
Groups C, D: dosing interval is 8 hours  
 
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) 
◼ 
Groups A, B, C, Control: AUC0-tau,ss on Day 15/AUC0-tau on Day 1 
◼ 
Group D: AUC0-tau,ss on Day 8/AUC0-tau on Day 1 
 
Fluctuation index (DF): Percent fluctuation at steady state = 100 × (Cmax,ss – 
Cmin,ss)/Cavg,ss 


Protocol No.TNP-2198-06 
Page 9 of 17 
Note: The apparent volume of distribution (Vd/F) and apparent clearance (CL/F) 
are not applicable to the analysis of pharmacokinetic parameters of the main 
metabolites. 
Evaluation of 
Helicobacter Pylori 
Eradication 
Group A, Group B, Group C and Control Group: 
The 14C UBT are performed on participants under fasting conditions before 
breakfast at screening (D-14 to D-2), baseline (D-1), day 8 (D8), day 16 (D16) and 
day 44 to 50 (D44 to D50) to evaluate the effect of H. pylori eradication in each 
group. 
Group D: 
The 14C UBT will be performed on participants under fasting conditions before 
breakfast at screening (D-14 to D-2), baseline (D-1), Day 8 (D8) and Day 37 to 43 
(D37 to D43) to evaluate the effect of H. pylori eradication. 
Statistical Analysis 
Definition of Statistical Analysis Set: 
 
Full Analysis Set (FAS): Refers to the participant of all randomized 
participants who have taken the investigational product at least once; 
 
Modified Intent-to-Treat Analysis Set (mITT): Refers to all randomized 
participants who have 14C UBT performed on Day 28 to 34 after the last dose 
of the study; 
 
Per Protocol Set (PP): Refers to participants without major protocol violation: 
participants who are randomized and receive more than 80% (inclusive) of the 
expected total amount of investigational product, and undergo 14C UBT on 
Day 28 to 34 after the last dose of the study; 
 
Safety Analysis Set (SS): refers to the participant participant who entered the 
study and used the investigational product at least once; 
 
Pharmacokinetic Concentration Analysis Set (PKCS): refers to all enrolled 
participants who have used the investigational product and have at least one 
observed PK concentration data; 
 
Pharmacokinetic Parameter Analysis Set (PKPS): refers to all enrolled 
participants who have used the investigational product and have at least one 
observed PK parameter data. 
 
Demographic Analysis: 
Demographic analyses are based on the Full Analysis Set (FAS). Descriptive 
statistics will be performed for all demographics (age, gender, weight, height, BMI, 
ethnicity, etc.) and baseline characteristics, taking the last valid measurement data 
before the administration of the investigational product as the baseline. 
 
Analysis of Helicobacter pylori eradication effect: 
The eradication effect will be analyzed descriptively by frequency (percentage) 
according to four 14C UBT results (negative or positive) at baseline, Day 8, Day 16, 
and Day 44 to 50 of follow-up in Group A, Group B, Group C and the Control 
Group, and three 14C UBT results (negative or positive) at baseline, Day 8, and Day 
37 to 43 of follow-up in Group D, based on the full analysis set (FAS). And make 
inter-group comparison, which shall focus on comparison between the test group 
and the control group, supplemented by the comparison among the test groups. 
Inter-group comparison of percentages will adopt Fisher's exact test. H. pylori 
eradication rate is defined as the proportion of participants with negative 14C UBT 
results from Day 28 to Day 34 after the last dose of the study. At the same time, the 
H. pylori eradication rate of each group will be calculated in the mITT analysis set 
and the PP analysis set, and the sensitivity analysis will be performed. 
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-2198-06 
Page 10 of 17 
Safety Analysis: 
The analysis of safety and tolerability are mainly based on descriptive statistics. 
AEs, treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), 
drug-related AEs and AEs leading to withdrawal from the study are summarized. 
The number, frequency and incidence of all adverse events will be tabulated and 
summarized by different groups, system organ class and preferred term. 
The number, frequency and incidence of adverse events of each grade will be 
tabulated according to CTCAE grade by different groups. 
The number, frequency and incidence of AEs in each group will be tabulated by 
system organ class and preferred term according to severity and relevancy to the 
investigational product. 
The number, frequency and incidence of common adverse events in each group 
will be tabulated and described by system organ class and preferred term. 
Laboratory test results that were normal before the test but abnormal after 
treatment are described by group. 
The mean, standard deviation, median, minimum and maximum values of vital 
signs (blood pressure, respiration, pulse and body temperature) and laboratory 
indicators before and after administration are calculated respectively by different 
groups. 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 Analysis: 
Non-compartmental pharmacokinetic parameters are estimated and analyzed for 
plasma concentration data using Phoenix WinNolin software, PK concentration 
data are analyzed using PKCS, and main pharmacokinetic parameters are 
calculated using PKPS data. Participants with serious deviations from the study 
protocol should be excluded from the pharmacokinetic analysis. 
The results of the analysis of the main pharmacokinetic parameters are summarized 
by groups using sample size, arithmetic mean, standard deviation, coefficient of 
variation, median, minimum, maximum and geometric mean and geometric 
coefficient of variation. Main pharmacokinetic parameters include: PK parameters 
of the first dose, such as Tmax, Cmax, t1/2, AUC0-∞, AUC0-tau, Vd/F, CL/F, etc.; PK 
parameters of the last dose, including Tmax,ss, Cmax,ss, Cmin,ss, Cavg,ss, t1/2,ss, AUC0-last,ss, 
AUC0-tau,ss, AUC0-∞,ss, V/Fss, CL/Fss, Rac, DF, etc. 
 


Protocol No.: TNP-2198-06 
  
Page 11 of 17 
Study Design 
 
Note: 14C UBT will also be performed for Group D during the screening period, the baseline period, and on Day 8 during the hospitalization/dosing period. 
 
 
Group A, Group B, Group C and Control 
Group 
Hospitalization/Dosing period 
Baseline 
period 
Follow-up 
period 
Screening 
period 
Randomi
zation 
Discharge may 
be allowed after 
completion of 
examinations 
and PK blood 
collection 
Return to the 
study center 
for 14C UBT 
  
Oral 
administration of 
the last dose of 
the investigational 
product according 
to the dosing 
regimen 
Daily oral administration of the investigational product for 
14 consecutive days according to the dosing regimen 
Day -14 to Day -
2 
Day -1 
Day 1 
Day 17 
…………………………………………………… 
Day 44 to 
Day 50 
Day 14 
Day 15 
End 
of 
Stud
y 
Group A 
TNP-2198 Capsules 400 mg, Rabeprazole Sodium Enteric-coated Tablets 20 
mg, Amoxicillin Capsules 1 g 
Twice daily
Group B 
TNP-2198 Capsules 600 mg, Rabeprazole Sodium Enteric-coated Tablets 20 
mg, Amoxicillin Capsules 1 g 
Twice daily 
Group C 
TNP-2198 Capsules 600 mg, Rabeprazole Sodium Enteric-coated Tablets 20 
mg 
Three times daily 
Control group 
Rabeprazole Sodium Enteric-coated Tablets 20 mg, Amoxicillin Capsules 1 
g 
Twice daily 
Group D  
Hospitalization/Dosing period 
Baseline 
period 
Follow-up 
period 
Screening 
period 
Randomiz
ation 
Discharge may 
be allowed after 
completion of 
examinations 
and PK blood 
collection 
Return to the 
study center 
for 14C UBT 
  
Oral 
administration of 
the last dose of 
the 
investigational 
product 
according to the 
dosing regimen 
Daily oral administration of the 
investigational product for 7 
consecutive days according to the 
dosing regimen 
Day -14 to Day -
2 
Day -1 
Day 1 
Day 10 
……………………… 
Day 34 to 
Day 43 
Day 7 
Day 8 
End 
of 
Stud
y 
Group D 
TNP-2198 Capsules 600 mg, Rabeprazole 
Sodium Enteric-coated Tablets 20 mg, 
Amoxicillin Capsules 1 g 
Three times daily 
Note: 14C UBT will also be performed for Group A, Group B, Group C and Control Group during the screening period, the baseline 
period, and on Day 8 and Day 16 during the hospitalization/dosing period. 


Protocol No.: TNP-2198-06 
  
Page 12 of 17 
Schedule of Activities for Group A, Group B, Group C and Control Group 
Study Procedures 
Screening 
period 
Baseline 
period 
Hospitalization/Dosing period 
Follow-up 
period 
D-14～D-2 
D-1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D9 
D10 D11 D12 D13 D14 D15 D16 D17 
D44～D50 
Screening 
Signing of ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and surgical 
history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chest plain X-ray1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abdominal Dopler 
ultrasound2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infectious disease 
screening3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Breath alcohol test 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screening4 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test5 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Verification of 
inclusion and 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Enrollment 
Admission 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study 
treatment 
administration 
Dosing6 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 


Protocol No.: TNP-2198-06 
  
Page 13 of 17 
Study Procedures 
Screening 
period 
Baseline 
period 
Hospitalization/Dosing period 
Follow-up 
period 
D-14～D-2 
D-1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D9 
D10 D11 D12 D13 D14 D15 D16 D17 
D44～D50 
Safety and 
tolerability 
assessment 
Clinical laboratory 
tests7 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
Physical examination8 
X 
X 
 
 
 
X 
 
X 
 
X 
 
 
 
X 
 
 
 
 
X 
 
12-lead ECG9 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
Vital signs10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Recording of adverse 
events 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK sample 
collection 
Blood sample11 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
Hp eradication 
assessment 
14C UBT12 
X 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
X 
 
X 
End of study 
Discharge13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Follow-up, study 
completion14 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
1 
Results of chest plain X-ray within 1 year prior to screening are acceptable. 
2 
Abdominal Dopler ultrasound includes digestive system and urinary system, and the results within 1 month prior to screening are acceptable. 
3 
Infectious disease screening includes hepatitis B serologic test, hepatitis C antibody, HIV antigen/antibody, and treponema pallidum antibody tests (an additional rapid 
plasma regain (RPR) test is required in patients positive for treponema pallidum antibody), and the test results within 3 months prior to screening are acceptable. 
4 
Urine drug screening (morphine, and marijuana) is performed at baseline (Day -1). 
5 
The serum pregnancy test is performed only for female participants during the screening period (Day -14 to Day -2) and the baseline period (Day -1) and on Day 17. 
6 
Oral administration is started on Day 1 for 14 consecutive days, during which 
a) 
Group A, Group B and Control Group each are given two oral doses each day, with breakfast and dinner within 30 min prior to dosing; the last dose of 
investigational product is given after breakfast on Day 15, with a total of 29 doses of the investigational product; 
b) 
Group C is given three oral doses each day at an interval of 8 h, and the last dose of investigational product is given in the morning on Day 15, with a total of 43 
doses of the investigational product. 
7 
Clinical laboratory tests include hematology, urinalysis, blood biochemistry and coagulation function, which are carried out during the screening period (Day -14 to Day 
-2), and the baseline period (Day -1), and before the first dose each on Day 2, Day 4, Day 6, Day 8, Day 10, Day 12 and Day 14 and on Day 17 (48 h after dosing on Day 
15). The test results obtained within 7 days of the screening period are acceptable for the baseline period, and no additional examination is required. 


Protocol No.: TNP-2198-06 
  
Page 14 of 17 
8 
Physical examinations include skin, mucosa, lymph nodes, head, neck, chest, abdomen, and spine/limbs, which are carried out during the screening period (Day -14 to 
Day -2), and the baseline period (Day -1), and on Day 4, Day 6, Day 8, Day 12 and Day 17. 
9 
The 12-lead ECG examination is performed during the screening period (Day -14 to Day -2), and the baseline period (Day -1), 2 h after the first dose on Day 1, within 60 
min before dosing on Day 15 and 2 h and 48 h (Day 17) after the dosing. 
10 Vital sign tests include blood pressure, pulse, body temperature and respiration, which are carried out during the screening period (Day -14 to Day -2), and the baseline 
period (Day -1), within 60 min before the first dose on Day 1 and 0.5, 2, 4, 8 and 12 h after the dosing, within 60 min before the first dose each from Day 2 to Day 14, 
within 60 min before dosing on Day 15 and 0.5, 2, 4, 8, 12, 24 h (Day 16) and 48 h (Day 17) after the dosing. 
11 PK blood collection time: 
a) 
Group A, Group B, and Control Group: within 30 min before dosing on Day 1 and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11 and 12 h (before the second dose 
on the day) after the dosing, within 30 min before dosing each on Day 3, Day 5, Day 7, Day 9, Day 11, Day 13 and Day 14, within 30 min before dosing on Day 15 
and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 24 h (Day 16) and 48 h (Day 17) after the dosing. 
b) 
Group C: within 30 min before dosing on Day 1 and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7 and 8 h after the dosing, within 30 min before dosing each on Day 3, Day 5, 
Day 7, Day 9, Day 11, Day 13 and Day 14, within 30 min before dosing on Day 15 and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 24 h (Day 16) and 48 h 
(Day 17) after the dosing. 
12 Participants are required to undergo the 14C UBT in the fasting state before breakfast during the screening period (Day -14 to Day -2), and the baseline period (Day -1), 
on Day 8 and Day 16 and during the follow-up period (Day 44 to Day 50). 
13 After all examinations and PK blood collection are completed on Day 17, participants may be discharged from the study center. 
14 Participants are required to return to the study center for follow-up visits from Day 44 to Day 50. Adverse events and laboratory abnormalities are followed up until the 
complete response or the return to baseline levels, the assessment of safety and tolerability is performed, and 14C UBT is performed to evaluate the effect of Hp 
eradication. 
 
 


Protocol No.: TNP-2198-06 
  
Page 15 of 17 
Schedule of Activities for Group D 
Study Procedures 
Screening period 
Baseline 
period 
Hospitalization/Dosing period 
Follow-up 
D-14～D-2 
D-1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D9 
D10 
D37～D43 
Screening 
Signing of ICF 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and surgical history 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chest plain X-ray1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Abdominal Dopler 
ultrasound2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Infectious disease screening3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Breath alcohol test 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screening4 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test5 
X 
X 
 
 
 
 
 
 
 
 
 
X 
 
Verification of inclusion and 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Enrollment 
Admission 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Study treatment 
administration 
Dosing6 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Safety and 
tolerability 
assessment 
Clinical laboratory tests7 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Physical examination8 
X 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
12-lead ECG9 
X 
X 
X 
 
 
 
 
 
 
X 
 
X 
 
Vital signs10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 


Protocol No.: TNP-2198-06 
  
Page 16 of 17 
Study Procedures 
Screening period 
Baseline 
period 
Hospitalization/Dosing period 
Follow-up 
D-14～D-2 
D-1 
D1 
D2 
D3 
D4 
D5 
D6 
D7 
D8 
D9 
D10 
D37～D43 
Recording of adverse events 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK sample 
collection 
Blood sample11 
 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
 
Hp eradication 
assessment 
14C UBT12 
X 
X 
 
 
 
 
 
 
 
X 
 
 
X 
End of study 
Discharge13 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Follow-up, study 
completion14 
 
 
 
 
 
 
 
 
 
 
 
 
X 
1 
Results of chest plain X-ray within 1 year prior to screening are acceptable. 
2 
Abdominal Dopler ultrasound includes digestive system and urinary system, and the results within 1 month prior to screening are acceptable. 
3 
Infectious disease screening includes hepatitis B serologic test, hepatitis C antibody, HIV antigen/antibody, and treponema pallidum antibody tests (an additional rapid plasma regain (RPR) 
test is required in patients positive for treponema pallidum antibody), and the test results within 3 months prior to screening are acceptable. 
4 
Urine drug screening (morphine, and marijuana) is performed at baseline (Day -1). 
5 
The serum pregnancy test is performed only for female participants during the screening period (Day -14 to Day -2) and the baseline period (Day -1) and on Day 10. 
6 
Starting from Day 1, three oral doses are given each day for 7 consecutive days, at an interval of 8 h. The last dose is given in the morning of Day 8, and each participant receives 22 doses 
of the investigational product. 
7 
Clinical laboratory tests include hematology, urinalysis, blood biochemistry and coagulation function, which are carried out during the screening period (Day -14 to Day -2), and the baseline 
period (Day -1), before the first dose each on Day 2, Day 4 and Day 6, before the first dose on Day 8 and on Day 10 (48 h after dosing on Day 8). The test results obtained within 7 days of 
the screening period are acceptable for the baseline period, and no additional examination is required. 
8 
Physical examinations include skin, mucosa, lymph nodes, head, neck, chest, abdomen, and spine/limbs, which are carried out during the screening period (Day -14 to Day -2), and the 
baseline period (Day -1), and on Day 4, Day 6, Day 8 and Day 10. 
9 
The 12-lead ECG examination is performed during the screening period (Day -14 to Day -2), and the baseline period (Day -1), 2 h after the first dose on Day 1, within 60 min before dosing 
on Day 8 and 2 h and 48 h (Day 10) after the dosing. 
10 
Vital sign tests include blood pressure, pulse, body temperature and respiration, which are carried out during the screening period (Day -14 to Day -2), and the baseline period (Day -1), 
within 60 min before the first dose on Day 1 and 0.5, 2, 4, 8 and 12 h after the dosing, within 60 min before the first dose each from Day 2 to Day 7, within 60 min before dosing on Day 8 
and 0.5, 2, 4, 8, 12, 24 h (Day 9) and 48 h (Day 10) after the dosing. 
11 
PK blood collection time: within 30 min before dosing on Day 1 and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7 and 8 h (before the second dose on the day) after the dosing, within 30 min before 
dosing each on Day 3, Day 5 and Day 7, within 30 min before dosing on Day 8 and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 11, 12, 24 h (Day 9) and 48 h (Day 10) after the dosing. 
12 
Participants are required to undergo the 14C UBT in the fasting state before breakfast during the screening period (Day -14 to Day -2), and the baseline period (Day -1), on Day 8 and during 
the follow-up period (Day 37 to Day 43). 
13 
After all examinations and PK blood collection are completed on Day 10, participants may be discharged from the study center. 


Protocol No.: TNP-2198-06 
  
Page 17 of 17 
14 
Participants are required to return to the study center for follow-up visits from Day 37 to Day 43. Adverse events and laboratory abnormalities are followed up until the complete response 
or the return to baseline levels, the assessment of safety and tolerability is performed, and 14C UBT is performed to evaluate the effect of Hp eradication.