PK, PD and Safety of Tegoprazan 12.5 mg After Oral Administration in Healthy Subjects

Phase 1 Clinical Trial to Explore Pharmacokinetics, Pharmacodynamics and Safety of Tegoprazan 12.5 mg After Oral Administration in Healthy Subjects

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Healthy
• Intervention / Treatment: Drug: Tegoprazan 12.5mg; Drug: Tegoprazan 25mg; Drug: Famotidine 20mg

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Tegoprazan 12.5mg	Drug: Tegoprazan 12.5mg; Oral administration of one tablet of Tegoprazan 12.5mg twice daily for 14 days.; Other Names: Tegoprazan Tab. 12.5mg
Active Comparator: Group B; Tegoprazan 25mg	Drug: Tegoprazan 25mg; Oral administration of one tablet of Tegoprazan 25mg once daily for 14 days.; Other Names: K-CAB Tab. 25mg
Active Comparator: Group C; Famotidine 20mg	Drug: Famotidine 20mg; Oral administration of one tablet of Famotidine 20mg twice daily for 14 days.; Other Names: Gaster Tab. 20 mg Dong-A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 1)	Pre-dose(0 hour) up to 24 hours on Day 1
AUC0-t of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 1)	Pre-dose(0 hour) up to 24 hours on Day 1
AUC0-∞ of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 1)	Pre-dose(0 hour) up to 24 hours on Day 1
Tmax of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 1)	Pre-dose(0 hour) up to 24 hours on Day 1
t1/2β of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 1)	Pre-dose(0 hour) up to 24 hours on Day 1
CL/F of tegoprazan	Pharmacokinetic evaluation (Day 1)	Pre-dose(0 hour) up to 24 hours on Day 1
Vd/F of tegoprazan	Pharmacokinetic evaluation (Day 1)	Pre-dose(0 hour) up to 24 hours on Day 1
Css,max of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 14)	Pre-dose(morning) (-12, 0 hour) up to 24 hours on Day 14
Css,min of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 14)	Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
Css,avg of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 14)	Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
AUCtau,ss of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 14)	Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
Tmax,ss of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 14)	Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
t1/2β,ss of tegoprazan and tegoprazan's metabolite M1	Pharmacokinetic evaluation (Day 14)	Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
CLss/F of tegoprazan	Pharmacokinetic evaluation (Day 14)	Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
Vdss/F of tegoprazan	Pharmacokinetic evaluation (Day 14)	Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
Accumulation index of tegoprazan	Pharmacokinetic evaluation (Day 14)	Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14
Fluctuation of tegoprazan	Pharmacokinetic evaluation (Day 14)	Pre-dose(morning)(-12, 0 hour) up to 24 hours on Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
24-hour, daytime and nighttime mean pH	Pharmacodynamic evaluation	24 hours on Day -1, Day 1, Day 7, and Day 14
24-hour, daytime and nighttime median pH	Pharmacodynamic evaluation	24 hours on Day -1, Day 1, Day 7, and Day 14
24-hour, daytime and nighttime TpH>3(%)	Pharmacodynamic evaluation	24 hours on Day -1, Day 1, Day 7, and Day 14
24-hour, daytime and nighttime TpH>4(%)	Pharmacodynamic evaluation	24 hours on Day -1, Day 1, Day 7, and Day 14
24-hour, daytime and nighttime Δ TpH>3(%)	Pharmacodynamic evaluation	24 hours on Day -1, Day 1, Day 7, and Day 14
24-hour, daytime and nighttime Δ TpH>4(%)	Pharmacodynamic evaluation	24 hours on Day -1, Day 1, Day 7, and Day 14
24-hour, daytime and nighttime Δ mean pH	Pharmacodynamic evaluation	24 hours on Day -1, Day 1, Day 7, and Day 14
24-hour, daytime and nighttime Δ median pH	Pharmacodynamic evaluation	24 hours on Day -1, Day 1, Day 7, and Day 14

Collaborators and Investigators

• Sponsor: HK inno.N Corporation
• Investigators: Principal Investigator: Jong Lyul Ghim, MD, PhD, Department of Clinical Pharmacology, Inje University Busan Paik Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 19, 2024
• Primary Completion (Estimated): July 31, 2024
• Study Completion (Estimated): July 31, 2024

Study Registration Dates

• First Submitted: February 20, 2024
• First Submitted That Met QC Criteria: March 20, 2024
• First Posted (Actual): March 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Histamine H2 Antagonists; Famotidine
• Other Study ID Numbers: IN_APA_124

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No