Conditions: Helicobacter Pylori Infection
Allocation: RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 40
Healthy volunteers: yes

Brief summary:
This study was a single-center, randomized, double-blind, placebo-controlled, dose-ascending multiple-dose-administration study. The aim of this study was to evaluate the safety, tolerability, and pharmacokinetic profile of TNP-2092 Capsules in asymptomatic healthy subjects with Helicobacter pylori infection, and to explore the preliminary efficacy of TNP-2092 Capsules in eradicating Helicobacter pylori.

Detailed description:
This study was a single-center, randomized, double-blind, placebo-controlled, dose-ascending multiple-dose-administration study. The aim of this study was to evaluate the safety, tolerability, and pharmacokinetic profile of TNP-2092 Capsules in asymptomatic healthy subjects with Helicobacter pylori infection, and to explore the preliminary efficacy of TNP-2092 Capsules in eradicating Helicobacter pylori.

In this study, three dose groups of 100 mg, 300 mg and 600 mg will be set up. The drug will be taken twice a day for 14 consecutive days, and last dose on the morning of Day 15. Fifteen subjects in each of the 100 mg and 300 mg dose groups will be randomized at a ratio of 4:1, with 12 subjects receiving the investigational product and 3 receiving placebo. Ten subjects in the 600 mg dose group will be randomized at a ratio of 4:1, with 8 subjects receiving the investigational product and 2 subjects receiving placebo.

Arms:
arm 1: Subjects received TNP-2092 capsules orally twice daily at the dose of 100 mg in the fed state for consecutive 14 days and received the last dose in the fed state on the morning of Day 15 arm 2: Subjects received TNP-2092 capsules orally twice daily at the dose of 300 mg in the fed state for consecutive 14 days and received the last dose in the fed state on the morning of Day 15 arm 3: Subjects received TNP-2092 capsules orally twice daily at the dose of 600 mg in the fed state for consecutive 14 days and received the last dose in the fed state on the morning of Day 15 arm 4: Subjects received TNP-2092 placebo capsules orally twice daily in the fed state for consecutive 14 days and received the last dose in the fed state on the morning of Day 15

Interventions: intervention 1: TNP-2092 capsules intervention 2: Placebo
Intervention descriptions: intervention 1: Administration orally. intervention 2: Administration orally.

Protocol document:
Prot_SAP_000.pdf: 
 
 
A phase 1, single-center, double-blind, placebo-controlled clinical trial to 
evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy 
of multiple oral administrations of TNP-2092 Capsules in asymptomatic 
healthy subjects with Helicobacter pylori infection 
 
 
 
 
Protocol 
 
 
 
 
Protocol No.: TNP-2092-03 
 
 
 
 
Approval Date: 25 July 2017 
 
 
 
 
ClinicalTrials.gov ID: NCT06190340 
 
 


Protocol of Study TNP-2092-03 
Name of Sponsor Company: TenNor 
Therapeutics (Suzhou) Limited. 
Individual Study 
Table Referring to 
Part of the Dossier 
Volume: 
Page: 
(For National Authority Use 
Only) 
Name of Finished Product: TNP-2092 
capsules 
Name of Active Ingredient: TNP-2092 
Title of study: A phase 1, single-center, double-blind, placebo-controlled clinical trial to evaluate 
the safety, tolerability, pharmacokinetics and preliminary efficacy of multiple oral administrations 
of TNP-2092 Capsules in asymptomatic healthy subjects with Helicobacter pylori infection 
Investigator: Yanhua Ding, The First Hospital of Jilin University 
Study center: The study will be conducted in a single center in China. 
Publication (Reference): None. 
Clinical Phase: 1 
Objectives 
1) 
To evaluate the safety and tolerability of multiple oral dose-escalation administrations of 
TNP-2092 Capsules in asymptomatic healthy subjects with Helicobacter pylori infection.  
2) 
To evaluate the pharmacokinetic characteristics of multiple oral dose-escalation 
administrations of TNP-2092 Capsules.  
3) 
To explore the preliminary efficacy of TNP-2092 Capsules in eradicating Helicobacter pylori 
through the 14C urea breath test (UBT). 
Methodology 
This study is a single-center, randomized, double-blind, placebo-controlled, dose-ascending 
multiple-dose-administration study. The aim of this study is to evaluate the safety, tolerability, and 
pharmacokinetic profile of TNP-2092 Capsules in asymptomatic healthy subjects with 
Helicobacter pylori infection, and to explore the preliminary efficacy of TNP-2092 Capsules in 
eradicating Helicobacter pylori. 
 
In this study, three dose groups of 100 mg, 300 mg and 600 mg will be set up. The drug will be 
taken twice a day for 14 consecutive days, and last dose on the morning of Day 15. Fifteen 
subjects in each of the 100 mg and 300 mg dose groups will be randomized at a ratio of 4:1, with 
12 subjects receiving the investigational product and 3 receiving placebo. Ten subjects in the 600 
mg dose group will be randomized at a ratio of 4:1, with 8 subjects receiving the investigational 
product and 2 subjects receiving placebo. 
 
During the trial, blood samples will be collected from the subjects at the specified time points for 
pharmacokinetic analysis. In the 300 mg group, urine and stool samples will be collected from 7 
subjects who are first enrolled in the group for metabolic transformation study. 
 
Plasma sample: 
 
Blood samples are collected at different time points. Day 1: before the first administration (within 
60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after administration; Day 15: before 
administration (within 60 minutes), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48 and 72 hours after 
administration; Days 2-14: before the first administration every day (within 60 minutes), the 
trough concentration is measured to monitor the complete pharmacokinetic changes. 
 
Urine sample (300 mg BID dose group - for 7 subjects who are first enrolled in the group only): 
 
Urine samples are collected before administration and 0-6 hours, 6-12 hours, 12-24 hours, 24-48 
hours and 48-72 hours after administration on Day 15 for metabolic transformation study. 


Name of Sponsor Company: TenNor 
Therapeutics (Suzhou) Limited. 
Individual Study 
Table Referring to 
Part of the Dossier 
Volume: 
Page: 
(For National Authority Use 
Only) 
Name of Finished Product: TNP-2092 
capsules 
Name of Active Ingredient: TNP-2092 
 
Stool sample (300 mg BID dose group - for 7 subjects who were first enrolled in the group only): 
 
Stool samples are collected within 72 hours after administration on Day 15 for metabolic 
transformation study. 
 
All of the subjects will be followed up by the 14C-urea breath test (UBT) to evaluate the 
eradication of Helicobacter pylori. 
Number of subjects 
It is planned to enroll 40 subjects, eight subjects will be administrated with placebo, and 32 
subjects will be administrated with TNP-2092 capsules (12 subjects each with 100 mg or 300 mg, 
and 8 subjects with 600 mg). 
Diagnosis and main criteria for inclusion 
Each subject will be required to meet all of the following criteria to be eligible for study 
enrollment: 
1) 
Those who are fully informed of and understand this study and have signed the Informed 
Consent Form. 
2) 
Those who are willing to follow and able to complete all the trial procedures. 
3) 
Female subjects of childbearing potential must agree to abstinence or take effective 
contraceptive measures during the trial and at least 70 days (10 weeks) after administration. 
4) 
Male subjects must agree to abstinence or use condoms as a contraceptive measure during 
the trial and at least 70 days (10 weeks) after administration. 
5) 
Sex: male or female. 
6) 
Age: 18-45 years, including 18 and 45 years.  
7) 
BMI: 19.0-26.0 kg/m2, including 19.0 and 26.0 kg/m2. 
8) 
Those who do not smoke, or have smoked less than 5 cigarettes per day within 3 months 
before screening; those who do not drink alcohol, or have drunk less than 14 units of alcohol 
per week (1 unit of alcohol = 360 mL of beer or 45 mL of spirits with 40% alcohol content or 
150 mL of wine) within 6 months before screening; those who have not smoked or drunk 
alcohol within 48 hours before admission to the study site.  
9) 
Subjects whose clinical laboratory test results are within the normal range or whose test 
results are abnormal but judged by the investigator to be of no clinical insignificance.  
10) Those with a positive 14C urea breath test (UBT) result. 
 
Subjects meeting any of the following criteria will be ineligible for study enrollment: 
1) 
Those with an allergic constitution, a history of allergic diseases or a history of drug allergy.  
2) 
Those with a history of alcohol or drug abuse in the past 10 years.  
3) 
Those who have donated blood within 3 months before enrollment.  
4) 
Those with regular use of any prescription/over-the-counter drugs, including vitamins, 
minerals, nutritional supplements or herbs, within 2 weeks before enrollment and during the 
study period.  
5) 
Those who have taken any drug that changes the activity of liver enzymes 28 days before 
taking the investigational product or during the study.  
6) 
Those who have participated in any clinical trials within 3 months before enrollment.  
7) 
Those with a history of eradication of Helicobacter pylori.  


Name of Sponsor Company: TenNor 
Therapeutics (Suzhou) Limited. 
Individual Study 
Table Referring to 
Part of the Dossier 
Volume: 
Page: 
(For National Authority Use 
Only) 
Name of Finished Product: TNP-2092 
capsules 
Name of Active Ingredient: TNP-2092 
8) 
Those who are suffering or have suffered from digestive tract diseases, including digestive 
tract ulcer, etc.  
9) 
Those with symptoms or past medical history of cardiovascular, respiratory, urinary, 
neurological, blood, immune, endocrine system diseases or tumor, mental illness, or any 
situation which, in the opinion of the investigator, may threaten the safety of the subjects or 
affect the correctness of the trial results.  
10) Those whose blood pressure remains above 140/90 mmHg after retest.  
11) Pregnant or lactating women.  
12) Those who are HIV positive, syphilis positive, hepatitis B surface antigen positive, hepatitis 
C antibody positive.  
13) Those who have had beverages or foods containing methylxanthine (coffee, tea, coke, 
chocolate, and energy drinks), grapefruit (fruit juice) and alcohol within 48 hours (2 days) 
before the clinical study.  
14) Other circumstances deemed by the investigator to be unsuitable for the subject to participate 
in this study. 
Investigational product, dose and regimen of administration 
Investigational product: TNP-2092 capsules. 
Dose and regimen of administration: Subjects will be administrated TNP-2092 capsules orally 
twice daily at the dose of 100 mg, 300 mg, and 600 mg in the fed state for consecutive 14 days 
and the last dose in the fed state on the morning of Day 15. 
Duration of treatment 
Approximately up to 63 days (from signing ICF to the end of the study). 
Reference treatment, dose and regimen of administration 
Placebo: TNP-2092 placebo capsules. 
Dose and regimen of administration: the same regimen as that of TNP-2092 capsules.  
Criteria for evaluation 
Pharmacokinetics 
Tmax, Cmax, t1/2, AUC0-∞, AUC0-last, AUC0-tau, Vd and CL, Tmax,ss, Cmax,ss, Cmin,ss, Cavg,ss, t1/2,ss, AUC0-
last,ss, AUC0-tau,ss, AUC0-∞,ss, Vss, CLss, accumulation index, fluctuation index, trough concentration. 
 
Safety 
incidence of AEs, the relationship between the drug and AEs, severity of AEs, physical 
examination, clinical laboratory tests (hematology, blood chemistry, coagulation, and urine test), 
vital signs (blood pressure, pulse and body temperature) and 12-lead ECG. 
 
Efficacy 
14C UBT. 
Statistical methods 
SAS 9.4 will be used for the statistical analysis. 
 
Sample size simulation 


Name of Sponsor Company: TenNor 
Therapeutics (Suzhou) Limited. 
Individual Study 
Table Referring to 
Part of the Dossier 
Volume: 
Page: 
(For National Authority Use 
Only) 
Name of Finished Product: TNP-2092 
capsules 
Name of Active Ingredient: TNP-2092 
This study is an early phase exploratory clinical trial, the sample size is not based on statistical 
hypothesis test. but based on the assessment of safety, PK, and preliminary efficacy in line with similar 
trails. The sample size of 15 patients in both of the 100 mg and 300 mg dose groups, and 10 patients in 
the 600 mg group are also appropriate for the purpose of the exploration of the PK profile, safety, and 
efficacy of TNP-2092 capsules. 
 
Population for analyses 
 
Full Analysis Set (FAS): all the subjects who have been randomized into groups. 
 
Safety Analysis Set (SS): all the subjects who have been randomized into groups and received at 
least one dose of study drug. 
 
PK Concentration Analysis Set (PKCS): all the subjects who have been randomized into groups, 
received at least one dose of study drug, and have at least one evaluable blood drug concentration. 
 
PK Parameter Analysis Set (PKPS): all subjects who have been randomized into groups, have 
received at least one dose of study drug, and have at least one evaluable pharmacokinetic 
parameter. 
 
Interim analysis 
No interim analysis is planned. 
 
PK analysis 
Pharmacokinetic analysis will be based on the PKPS. Pharmacokinetic concentration and 
parameters will be subjected to descriptive analysis by dose group. The mean and individual 
drug-time curves will be shown graphically. Numbers will include individual values and mean 
values. In addition, individual and mean dose standardization parameters will be plotted against 
the dose to evaluate whether there are any obvious trends. 
 
Safety and tolerability analysis 
It will be based on the SS. Physical examination results and changes, laboratory test results and 
changes, vital signs results and changes, as well as ECG results and changes will be descriptive 
analyzed by dose group and planned time point. The abnormal results of these examinations will 
also be listed. Adverse events (AEs) will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) and summarized by treatment group and dose according to the system 
organ class (SOC) and preferred terms (PTs). In addition, serious adverse events (SAEs) and AEs 
leading to dropout and death will be listed separately. 
 
Efficacy analysis 
The preliminary Helicobacter Pylori eradication efficacy will be analyzed based on FAS. The 
number and percentage of subjects with 14C UBT negative at the follow-up visit will be listed by 
dose group. Fisher's exact test was used for comparison of percentages between groups (if 
infeasible for data reasons, summarize only). For all measurements, the baseline values and 
changes from baseline will be summarized by dose group and visit. Changes from baseline will be 
compared between groups by visit using analysis of covariance model, with baseline value as 
covariate and treatment group as fixed effect factors. Missing values will be imputed using last 
observation carry forward (LOCF). Sensitivity analysis will be performed using mixed model for 
repeated measures (MMRM), with baseline value and treatment group as fixed effect factors. An 
unstructured covariance matrix will be preferred in the model, if not fitted, other suitable 
covariance matrix would be used. 


Appendix 1 
Study Flowchart 
Procedure 
Screening 
visit 
(Day -14 
to Day -3) 
Day 
-2 
Day -1 
Day 1 
Day 2-14 
Day 15 
Day 16 
Day 17 
Day 
18 
Follow-
up 
During 
Day 4 - 
49 1 
Screening 
 
 
 
 
 
 
 
 
 
 
Sign the ICF 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical and surgical history 
X 
X 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chest X-ray 
X 
 
 
 
 
 
 
 
 
 
Hepatitis B and hepatitis C tests 17 
X 
 
 
 
 
 
 
 
 
 
Syphilis test 
X 
 
 
 
 
 
 
 
 
 
HIV test 
X 
 
 
 
 
 
 
 
 
 
Alcohol breath test 
 
X 
 
 
 
 
 
 
 
 
Drug test 
 
X 
 
 
 
 
 
 
 
 
Blood pregnancy test 2 
X 
 
X 
 
 
 
 
 
X 
 
Verification of inclusion and 
exclusion criteria 
X 
X 
X 
 
 
 
 
 
 
 
14C urea breath test (UBT) 
X 
 
 
 
 
 
X3 
 
 
X 
Abdominal ultrasound (digestive 
system) 
X 
 
 
 
 
 
 
 
 
 
Fibro Touch test 
X 
 
 
 
 
 
 
 
 
 
Admission  
 
X 
 
 
 
 
 
 
 
 
Randomization 
 
 
X 
 
 
 
 
 
 
 
Tolerability evaluation 
 
 
 
 
 
 
 
 
 
 
Hematology/blood 
biochemistry/coagulation 4 
X 
 
X5 
 
X(pre- Day 
2,4,6,8,12) 
 
 
 
X(72 
h)11 
 


Procedure 
Screening 
visit 
(Day -14 
to Day -3) 
Day 
-2 
Day -1 
Day 1 
Day 2-14 
Day 15 
Day 16 
Day 17 
Day 
18 
Follow-
up 
During 
Day 4 - 
49 1 
Urinalysis 4 
X 
 
X5 
 
X(pre-Day 
2,4,6,8,12) 
 
 
 
X(72 
h)11 
 
Stool routine 4 
X 
 
X6 
 
X(Day 
2,4,6,8,12)7 
 
 
 
X8 
 
Physical examination 4 
X 
X 
 
 
X(Day 
4,6,8,12) 
 
 
 
X 
 
12-lead ECG 4 
X 
X14 
 
X(pre-60 min；post 
6h）10 
 
X(pre-60 min; post 6h)11 
 
 
X(72 
h)11 
 
Vital signs 4 
X 
X14 
 
X(pre-60 min；post 
0.5,2,4,8,12 h）10 
X(pre-60 
min) 
X(pre-60 min; post 
0.5,2,4,8,12 h)11 
X(24 h)11 
X(48 h)11 X(72 
h)11 
 
Monitoring and recording of 
adverse events 9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK sample collection 4 
  
 
  
  
  
 
 
 
 
 
Blood samples 
  
 
  
X(pre-60 min; post 
0.5,1,2,3,4,6,8,10,12 
h）10 
X (pre-60 
min) 
X(pre-60 min; post 
0.5,1,2,3,4,6,8,10,12,16 h）
11 
X(24,36 h)11 X(48 h)11 X(72 
h)11 
 
Urine samples 18 
 
 
 
 
 
X 
X 
X 
X 
 
Stool samples 18 
 
 
 
 
 
X 
X 
X 
X 
 
Investigational product distribution 
  
 
  
 
 
 
 
 
 
 
Administration 12 
  
 
  
X 
X 
X13 
 
 
 
 
Standard breakfast and dinner 
 
 
X 
X 
X 
X 
X 
X 
X15 
 
Discharge from the study site 
  
 
  
  
  
 
 
 
X 
 
Follow-up 
 
 
 
 
 
 
 
 
 
X16 
Abbreviations: PK = pharmacokinetics; Pre = before the first daily dose; Post = after the first daily dose; 
1. 
If a subject prematurely terminates the study after taking the drug, subsequent designated visits should be completed. 
2. 
Pregnancy test may be repeated during the course of the study, if deemed necessary by the investigator. 


3. 
UBT is performed before breakfast on Day 16. 
4. 
If multiple assessments are performed at the same time, it is recommended to collect samples/data in the following order in the non-emergency state (but subject to 
actual clinical practice): PK samples, ECGs, and vital signs; and then all the other assessments. ECGs, blood pressure, and pulse should be measured after the subject has 
rested for approximately 5 minutes. The subjects are required to fast overnight for 10 hours before blood biochemistry test; water was deprived for 1 hour before 
administration and 2 hours after administration. 
5. 
If hematology, urinalysis, blood chemistry, and coagulation tests were performed within 48 hours of screening, the results could be used as baseline values and no 
additional tests were required. 
6. 
If stool routine test was performed within 7 days of screening, the result could be used as the baseline value and no additional tests were required. 
7. 
If no stool specimen was collected on the specified day, the situation should be stated, and no additional collection was required. 
8. 
If no stool specimen was collected on that day, no additional collection was required. 
9. 
Adverse events should be followed up until they are resolved or until the investigator assesses the subject as having returned to baseline. 
10. Sampling/testing time (hours) was relative to the time of the first dose on the very day of the study. 
11. Sampling/testing time (hours) was relative to the dosing time on Day 15 of the study. 
12. Subjects received the drug orally twice daily after breakfast and dinner (the meals should be finished within 30 minutes and the drug should be administered 30 minutes 
after the start of the meal) with 240 mL of warm water, 12 hours apart. The initial dose was 100 mg twice daily after meals. After the administration for the 100 mg dose 
group and the evaluation of safety and tolerability were completed, the next dose group would be tested according to the principle of ascending until the maximum dose 
was reached or the predefined indication for study suspension occurred. 
13. The last dose was given 30 minutes after the start of breakfast on Day 15. 
14. The 12-lead ECG and vital signs measured before administration on D1 were used as baseline values. 
15. Subjects only had breakfast that day. 
16. Subjects were required to be in a fasting condition in the morning for the follow-up examinations at the clinical study site. 
17. Hepatitis B tests included hepatitis B virus surface antigen (HBsAg), hepatitis B virus surface antibody (HBsAb), hepatitis B virus e antigen (HBeAg), hepatitis B virus 
e antibody (HBeAb), and hepatitis B virus core antibody (HBcAb). The hepatitis C test is a hepatitis C virus antibody test. 
18. Specimens were collected from the first 7 subjects enrolled in the 300 mg dose group.