Clinical trial NCT06332638: PK, PD and Safety of Tegoprazan 12.5 mg After Oral Administration in Healthy Subjects
Official title: Phase 1 Clinical Trial to Explore Pharmacokinetics, Pharmacodynamics and Safety of Tegoprazan 12.5 mg After Oral Administration in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Healthy
Lead sponsor: HK inno.N Corporation
Sponsor class: INDUSTRY
First posted: 2024-03-27
Enrollment: 36
Sex: ALL
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to explore pharmacokinetics, pharmacodynamics, and safety of tegoprazan 12.5 mg in healthy subjects when orally administered as a single dose or as multiple doses twice daily.

Detailed description: The secondary objectives of this study are

* To compare pharmacokinetics and pharmacodynamics of tegoprazan 12.5 mg in healthy subjects between oral multiple-dose administration twice daily for 1 day and oral single-dose administration.
* To evaluate pharmacokinetics and pharmacodynamics of tegoprazan 12.5 mg administered orally twice daily for 14 days in healthy subjects in comparison with tegoprazan 25 mg administered orally once daily for 14 days in healthy subjects.
* To evaluate pharmacodynamics of tegoprazan 12.5 mg administered orally twice daily for 14 days or tegoprazan 25 mg administered orally once daily for 14 days in healthy subjects in comparison with famotidine 20 mg administered orally twice daily for 14 days in healthy subjects.

Eligibility criteria: Inclusion Criteria:

1. Healthy adults aged ≥ 19 years to ≤ 45 years at the time of screening testing
2. Body mass index (BMI) ≥ 18.5 kg/m2 to ≤ 28.0 kg/m2 (BMI = weight (kg) / height (m)2)
3. Those who have been fully informed of study purpose and procedures, properties of the investigational products(IPs), etc. and have voluntarily decide to participate in this study and signed an informed consent form (ICF), prior to participation in the study

Exclusion Criteria:

1. Medical history

   1. Previous history or presence of clinically significant hepatic, renal, gastrointestinal, respiratory, musculoskeletal, endocrine, neuropsychiatric, hemato-oncologic, urinary and cardiovascular (including cardiac arrhythmia) disorders in the judgment of the investigator
   2. Previous history of gastrointestinal diseases (e.g., gastritis, gastrospasm, gastroesophageal reflux disease (GERD), Crohn's disease, ulcers, etc.) or abdominal surgery (excluding simple appendectomy or hernia surgery) which may affect drug absorption in the judgment of the investigator
   3. Presence of anatomical disorders that make it difficult to insert and maintain a catheter for intragastric pH measurement, or expected intolerance to catheterization for intragastric pH measurement
   4. Hereditary problems such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
2. Clinical laboratory tests and electrocardiogram (ECG)

   1. AST or ALT value ≥ 1.5 x upper limit of normal (ULN) as a result of clinical laboratory testing at screening
   2. Total bilirubin value ≥ 2.0 x upper limit of normal (ULN) as a result of clinical laboratory testing at screening
   3. eGFR value calculated using the CKD-EPI formula \< 80 mL/min as a result of clinical laboratory testing at screening
   4. Any clinically significant abnormality as a result of ECG at screening
   5. Positive test result for H. pylori at screening
3. Allergies and drug abuse

   1. History of hypersensitivity to the IPs, components of the IPs, and other drugs (benzimidazoles, H2 receptor antagonists, aspirin, antibiotics, etc.)
   2. Previous history of drug abuse or positive drug screening test result
4. Prohibited concomitant medications/diets

   1. Consumption of medicines (including herbal medicines) or abnormal diets (e.g., at least 1L/day of grapefruit juice, much garlic, broccoli, kale, etc.) which may affect the absorption, distribution, metabolism, and excretion of the IP within 28 days before the screening visit
   2. Administration of the drugs affecting gastric pH within 14 days before the screening visit (including potassium-competitive acid blockers, proton pump inhibitors, H2-receptor antagonists, and antacids) or administration of ethical-the-counter (ETC) drugs, any over-the-counter (OTC) drugs, vitamins, etc. within 10 days before the screening visit
   3. Administration of another IP by participating in another clinical trial within 6 months prior to the screening visit (but those who are not administered the IP can participate in this study)
5. Blood donation and transfusion

   1. Whole blood donation within 60 days before the screening visit
   2. Blood component donation or transfusion within 30 days before the screening visit
6. Pregnancy, breastfeeding, and non-use of contraceptives

   1. Pregnant women, women who tested positive for pregnancy, or breastfeeding women
   2. Failure to use medically recognized and proper double contraceptive methods or medically acceptable contraceptive methods (intrauterine device showing a demonstrated pregnancy failure rate, combined use of physical barrier method and spermicide, vasectomy, salpingectomy/tubal ligation, hysterectomy, etc.) in the subject or his/her spouse or partner from the date of screening visit until 30 days after the last dose of the IP
7. Others

   1. Mean alcohol intake exceeding 30 g/day per week for recent 4 weeks before the screening visit or positive alcohol breath test result
   2. Mean number of smoked cigarettes exceeding 10 cigarettes/day per week for recent 4 weeks before the screening visit
   3. Mean caffeine intake exceeding 400 mg/day per week for recent 4 weeks before the screening visit
   4. Presence of clinically significant findings that make the subject ineligible for this study in the judgment of the investigator

Primary outcomes:
measure: Cmax of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(0 hour) up to 24 hours on Day 1
measure: AUC0-t of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(0 hour) up to 24 hours on Day 1
measure: AUC0-∞ of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(0 hour) up to 24 hours on Day 1
measure: Tmax of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(0 hour) up to 24 hours on Day 1
measure: t1/2β of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(0 hour) up to 24 hours on Day 1
measure: CL/F of tegoprazan
timeFrame: Pre-dose(0 hour) up to 24 hours on Day 1
measure: Vd/F of tegoprazan
timeFrame: Pre-dose(0 hour) up to 24 hours on Day 1
measure: Css,max of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(morning) (-12, 0 hour) up to 24 hours on Day 14
measure: Css,min of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
measure: Css,avg of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
measure: AUCtau,ss of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
measure: Tmax,ss of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
measure: t1/2β,ss of tegoprazan and tegoprazan's metabolite M1
timeFrame: Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
measure: CLss/F of tegoprazan
timeFrame: Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
measure: Vdss/F of tegoprazan
timeFrame: Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
measure: Accumulation index of tegoprazan
timeFrame: Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
measure: Fluctuation of tegoprazan
timeFrame: Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
Secondary outcomes:
measure: 24-hour, daytime and nighttime mean pH
timeFrame: 24 hours on Day -1, Day 1, Day 7, and Day 14
measure: 24-hour, daytime and nighttime median pH
timeFrame: 24 hours on Day -1, Day 1, Day 7, and Day 14
measure: 24-hour, daytime and nighttime TpH>3(%)
timeFrame: 24 hours on Day -1, Day 1, Day 7, and Day 14
measure: 24-hour, daytime and nighttime TpH>4(%)
timeFrame: 24 hours on Day -1, Day 1, Day 7, and Day 14
measure: 24-hour, daytime and nighttime Δ TpH>3(%)
timeFrame: 24 hours on Day -1, Day 1, Day 7, and Day 14
measure: 24-hour, daytime and nighttime Δ TpH>4(%)
timeFrame: 24 hours on Day -1, Day 1, Day 7, and Day 14
measure: 24-hour, daytime and nighttime Δ mean pH
timeFrame: 24 hours on Day -1, Day 1, Day 7, and Day 14
measure: 24-hour, daytime and nighttime Δ median pH
timeFrame: 24 hours on Day -1, Day 1, Day 7, and Day 14
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Inje University Busan Paik Hospital
Study officials:
affiliation: Department of Clinical Pharmacology, Inje University Busan Paik Hospital
name: Jong Lyul Ghim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: