Clinical trial NCT05915871: Drug Interaction Study Between Tegoprazan, Bismuth, Amoxicillin and Clarithromycin
Official title: An Open-label, Fixed-sequence Study to Evaluate the Drug-drug Interactions Between Tegoprazan Tablets and Bismuth Potassium Citrate Capsules, Amoxicillin Capsules, and Clarithromycin Tablets in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Shandong Luoxin Pharmaceutical Group Stock Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-06-23
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the pharmacokinetic interaction between tegoprazan and combination of Amoxicillin, Clarithromycin and bismuth in healthy adult volunteers.

Detailed description: To evaluate the pharmacokinetic interaction between tegoprazan and combination of Amoxicillin, Clarithromycin and bismuth in healthy adult volunteers.

Eligibility criteria: Inclusion Criteria:

* 1. Subjects fully understand the objectives, nature, method, possible AEs of the trial, voluntarily participate in this clinical study, sign the ICF in person prior to the start of any study procedure, and promise that they will participate in all the study procedures in person.

  2. Chinese healthy male and non-lactating female subjects who are 18 to 55 years of age (inclusive) at the signing of ICF.

  3. Body mass index (BMI) of 19.0 to 28.0 kg/m2 (inclusive); and male weight ≥ 50.0 kg, female weight ≥ 45.0 kg.

  4. Subjects can communicate well with the investigator and understand and comply with various requirements of the study.

Exclusion Criteria:

* 1. Diseases with prior and current abnormal clinical manifestations to be excluded, including but not limited to diseases of the nervous system, cardiovascular system, blood and lymphatic system, immune system, kidney, liver, gastrointestinal tract, respiratory system, metabolism, and bones.

  2. People with a history of specific allergy (asthma, urticaria, eczema, etc.), an allergic constitution, or known hypersensitivity to tegoprazan, bismuth potassium citrate, amoxicillin, clarithromycin, penicillin, and macrolide antibiotics, or hypersensitivity to any ingredient of the drug products.

  3. Positive reaction to penicillin skin test. 4. History of active ulcer or significant hemorrhage from gastrointestinal tract, genitourinary tract or respiratory tract, or central nervous system hemorrhage.

  5. History of dysphagia or any gastrointestinal disorder affecting drug absorption (as judged by the investigator).

  6. Surgery within 3 months prior to screening, or planning to receive surgery during the study, and history of any surgery that may affect drug absorption (e.g., gastrectomy).

  7. Intolerance to venipuncture, or history of fear of needles or blood. 8. Lactose intolerance (history of diarrhea due to drinking milk). 9. History of illicit drug abuse within 6 months prior to screening, history of illicit drug use, or urine drug screen test positive.

  10. Mean alcohol use \> 14 units of alcohol (1 unit of alcohol ≈ 360 mL of beer, 150 mL of wine, or 45 mL of spirit) per week within 3 months prior to screening, or alcohol breath test positive, or inability to stop drinking during the trial period.

  11. Mean daily smoking \> 5 cigarettes within 3 months prior to screening, or inability to stop using any tobacco products during the trial period.

  12. Participation in any clinical trial of other investigational drug/device within 3 months prior to the first dose of study drug, or participation in 3 or more drug/device clinical trials in the past one year; if the half-life of other study drugs is long (5 half-lives exceed 3 months), the time interval required will be longer, i.e., 5 half-lives of the drug.

  13. Blood donation including donating blood components or massive blood loss (≥ 200 mL) within 3 months prior to screening; blood transfusion or use of blood products within 3 months prior to screening.

  14. History of vaccination within 1 month prior to screening, or planned vaccination during the study period.

  15. Use of any drugs inhibiting or inducing hepatic drug metabolism within 28 days prior to first dose of study drug.

  16. Use of any prescription drugs, over-the-counter drugs, dietary supplements, or Chinese herbal medicines within 14 days prior to first dose.

  17. Any of the hepatitis B surface antigen, hepatitis C virus antibody, anti-human immunodeficiency virus antibody, or anti-Treponema pallidum specific antibody tests is positive.

  18. At the time of screening, the results of vital signs (blood pressure, pulse rate, and body temperature), physical examination, and laboratory tests (complete blood count, blood chemistry, coagulation, and urinalysis) are judged as abnormal and clinically significant by the investigator.

  19. In the supine 12-lead ECG performed after at least 10 minutes of quiet rest during screening, QT interval corrected by Fridericia's formula (QTcF) \> 470 msec (female)/450 msec (male) \[Fridericia's formula is QTcF = QT/(RR)1/3\] or QRS complex \> 120 msec \[if the QTcF of the 1st measurement exceeds 450 msec (female QTcF \> 470 msec) or QRS \> 120 msec, 12-lead ECG measurements should be repeated 2 times, and a judgment should be made using the mean QTcF or QRS value of the 3 measurements\].

  20. Subjects with a history of prolonged QT interval or ventricular arrhythmia (including torsade de pointes).

  21. Subjects with hypokalemia (at risk of prolonged QT interval). 22. Creatinine clearance (CLCr) \< 90 mL/min. The calculation method of creatinine clearance is shown in Appendix 4.

  23. Subjects who cannot stop taking strenuous exercise within 48 hours prior to first dose of study drug and during the trial period.

  24. Subjects who consume any alcohol-containing, caffeine-containing, or xanthine-rich food or beverage within 48 hours prior to first dose of study drug; or cannot stop consuming such products during the trial period.

  25. Subjects who consume pitaya, mango, grapefruit, or grapefruit-related citrus fruits (e.g., pomegranate, starfruit, Seville orange, and pomelo) or food or beverage prepared from such fruits within 7 days prior to first dose of study drug, or cannot stop taking these fruits or food or beverage prepared from them during the trial period.

  26. Subject or his/her partner has planned parenthood, or is unwilling to take effective contraceptive measures (see Appendix 1 for details), or has a sperm or egg donation plan throughout the study and within 3 months after last dose of study drug. Female subjects who do not take effective contraceptive measures within 15 days prior to screening.

  27. Female subjects who have a positive blood pregnancy test at screening. 28. Unwillingness or inability to follow the lifestyle guidance (e.g., dietary restrictions and activity requirements) described in the study protocol.

  29. Subjects have other acute or chronic medical or psychiatric disorders and thereby are judged by the investigator as not suitable for participating in this study, which may increase the risk related to this study or may interfere with the interpretation of study results.

  30. Other subjects who are judged unsuitable for participation in the clinical trial by the investigator.

Primary outcomes:
measure: AUCtau of Tegoprazan, Bismuth, Amoxicillin, and Clarithromycin Following Multiple Oral Doses
timeFrame: Up to Day 27
measure: Cmax,ss of Tegoprazan, Bismuth, Amoxicillin, and Clarithromycin Following Multiple Oral Doses
timeFrame: Up to Day 27
Secondary outcomes:
measure: Tmax,ss of tegoprazan, bismuth, amoxicillin, and clarithromycin
timeFrame: Up to Day 27
measure: T1/2 of tegoprazan, bismuth, amoxicillin, and clarithromycin
timeFrame: Up to Day 27
measure: CL/F of tegoprazan, bismuth, amoxicillin, and clarithromycin
timeFrame: Up to Day 27
measure: Vdss/F of tegoprazan, bismuth, amoxicillin, and clarithromycin
timeFrame: Up to Day 27
measure: Cmax,ss of M1 (tegoprazan metabolite) and 14-hydroxyclarithromycin
timeFrame: Up to Day 27
measure: AUCtau of M1 (tegoprazan metabolite) and 14-hydroxyclarithromycin
timeFrame: Up to Day 27
measure: Tmax,ss of M1 (tegoprazan metabolite) and 14-hydroxyclarithromycin
timeFrame: Up to Day 27
measure: T1/2 of M1 (tegoprazan metabolite) and 14-hydroxyclarithromycin
timeFrame: Up to Day 27
measure: Number of Participants With Adverse Events
timeFrame: Up to Day 34
measure: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values
timeFrame: Up to Day 28
measure: Number of Participants With Clinically Notable Laboratory Tests
timeFrame: Up to Day 28
measure: Number of Participants With Clinically Notable Vital Signs
timeFrame: Up to Day 28
measure: Number of Participants With Clinically Notable Physical Exam
timeFrame: Up to Day 28
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
Study officials:
References: