A Study to Evaluate Pharmacokinetics/Pharmacodynamics and Safety/Tolerability of IN-C005 in Healthy Male Subjects

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate pharmacokinetics/pharmacodynamics and safety/tolerability of IN-C005 after oral administration in healthy Korean and Caucasian male subjects.

Detailed Description
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[Pharmacokinetic Assessments]: Plasma concentrations of IN-C005 and its metabolite will be measured Single Dosing Group (Korean Subjects) Primary endpoints: Cmax and AUClast of IN-C005 Secondary endpoints: AUClast, Cmax, AUCinf, Tmax, t½, CL/F, and Vd/F of M1; AUCinf, Tmax, t½, CL/F, and Vd/F of IN-C005 Multiple Dosing Group (Caucasian Subjects) Primary endpoints: Cmax, AUClast, Cmax,ss, and AUCτ,ss of IN-C005 Secondary endpoints: For M1, AUClast, Cmax, Cmax,ss, AUCinf, AUCτ,ss, Tmax, Tmax,ss, t½, CL/F, and Vd/F; for IN-C005, AUCinf, Tmax, Tmax,ss, Cmin,ss, t½, CL/F, Vd/F, Cav,ss, CLss/F, Vss/F, PTF (peak to trough fluctuation), and R (accumulation ratio) [Pharmacodynamic Assessments]: Single Dosing Group (Korean Subjects) Intragastric pH Percent (%) duration of pH ≥4 in 24 hrs Mean pH Median pH Change in pH from baseline to post-dose (Δduration %, Δmean pH, Δmedian pH, etc.) Serum gastrin level AUEGlast Gmax Change in gastrin level from baseline to study treatment (1d, 8d, and 15d)(ΔAUEGlast, ΔGmax, etc.) Multiple Dosing Group (Caucasian Subjects) Intragastric pH Percent (%) duration of pH ≥4 in 24 hrs Mean pH Median pH Change in pH from baseline to post-single dose and post-multiple doses (Δduration %, Δmean pH, Δmedian pH, etc.) Serum gastrin level AUEGlast Gmax Change in gastrin level from baseline to 1d and 7d (ΔAUEGlast, ΔGmax, etc.) [Safety Assessments] <Single Dosing Group (Korean Subjects) and Multiple Dosing Group (Caucasian Subjects)> AEs will be monitored with observable/objective symptoms, etc. Physical examination, vital signs, electrocardiogram (ECG), and clinical laboratory tests

Official Title
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An Open-label, Randomized, Single and Multiple Dosing Phase I Clinical Trial to Evaluate Pharmacokinetics/Pharmacodynamics and Safety/Tolerability of IN-C005 After Oral Administration in Healthy Korean and Caucasian Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: IN-C005 dose A
* Drug: IN-C005 dose B
* Drug: IN-C005 dose C
* Drug: IN-C005 dose D
* Drug: IN-C005 dose E
* Drug: IN-C005 dose F


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: [For single dosing group only] Healthy Korean male aged 19 to 50 years (inclusive) at the time of signing the informed consent form (ICF) [For multiple dosing group only] Healthy Caucasian male aged 19 to 50 years (inclusive) at the time of signing the ICF (Caucasian subject is defined as a European who was born in Europe, has the duration of residence outside of Europe less than 10 years, and both of whose parents and grandparents are European-born). Body mass index (BMI) of ≥ 18.0 and ≤ 28.0 kg/m2 with a body weight ≥ 55.0 kg at screening. (BMI (kg/m2) = weight (kg) / {height (m)}2) Subjects with negative result in serum Helicobacter pylori antibody test. Voluntary participation in the study after being fully informed of and understanding the study completely, and provides his written informed consent prior to screening procedure Subjects who are eligible for this study in the opinion of the investigator based on the results of physical examination, clinical laboratory tests, interview, etc. Exclusion Criteria: History or current evidence of clinically significant disorder of hepatic, renal, nervous, respiratory, endocrine, hemato-oncologic, cardiovascular, urinary, and/or psychiatric system. History or current evidence of gastrointestinal disease that may affect the safety and PD assessment for study treatment (e.g., gastrointestinal ulcer, gastritis, gastric cramp, gastroesophageal reflux disease, and Crohn's disease) or a history of gastrointestinal surgery (except for simple appendectomy or herniotomy). History or current evidence of clinically significant hypersensitivity to drugs containing IN-C005 or any ingredient of proton pump inhibitors and other drugs (such as aspirin and antibiotics). Subjects with positive result on serology tests (for hepatitis B, human immunodeficiency virus [HIV], and hepatitis C). Subjects with blood level of total bilirubin, AST (GOT), or ALT (GPT) > 1.5 X upper limit of normal range(ULN) at procedures performed during the screening period including those performed additionally. Subjects with eGFR < 60 ml/min/1.73m2 during the screening period including those performed additionally. Systolic blood pressure (SBP) of < 90 mmHg or > 140 mmHg, diastolic blood pressure (DBP) of < 50 mmHg or > 95 mmHg, or pulse rate of < 45 beats/min or > 100 beats/min on vital signs as measured in sitting position after taking a rest for at least 5 minutes at screening. Subjects with anatomical disorder that precludes insertion and maintenance of intragastric pH meter catheter or is expected to be intolerable to insertion of intragastric pH meter catheter. History of drug abuse or positive response to drug abuse on urine drug screening test. Subjects who received any prescription drug or herbal medication within 2 weeks of or any over-the-counter (OTC) drug, dietary supplements, or vitamins within 1 week of scheduled first dose or subjects who are expected to receive such medication during the study. (Note: a subject may participate in the study at the discretion of the investigator, provided that the subject meets all the other criteria). Subjects who participated in any other clinical study or bioequivalence study and received investigational product within 6 months prior to the scheduled first dose. Subjects who have donated whole blood within 2 months prior to the scheduled first dose, or have donated blood components or received transfusion within a month prior to the scheduled first dose. Excessive caffeine intake (> 5 units/day), continued use of alcohol (> 21 units/week, 1 unit = 10 g of pure alcohol), or inability to stop drinking while hospitalized. Positive result for cotinine on urine drug screening test or inability to quit smoking throughout the study. Subjects who have taken grapefruit-containing foods during the period from 24 hours (hrs) before hospitalization to discharge, or are unable to avoid grapefruit-containing foods during this period. Subjects who are unable to avoid caffeine-containing foods (e.g., coffee, tea [red tea, green tee, etc.], soda, coffee milk, and nutritive tonic drink) during the period from 24 hrs before hospitalization to discharge. Subjects who are unable to use medically acceptable contraceptive methods throughout the study. ► Medically acceptable contraceptive methods include: ① Use of intrauterine device with a proven birth control failure rate by the spouse (or partner); ② Simultaneous use of (male or female) barrier method and spermicide; and ③ Surgical sterilization of the subject or his partner (e.g., vasectomy, salpingectomy, tubal ligation, or hysterectomy). Subjects who are determined ineligible for study participation by the investigator for other reasons such as clinical laboratory abnormalities.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>IN-C005 dose A | Drug: IN-C005 dose A<br>* One time dose of IN-C005 dose A taken orally.<br>* Other names: IN-C005;|
| Experimental: Group B<br>IN-C005 dose B | Drug: IN-C005 dose B<br>* One time dose of IN-C005 dose B taken orally.<br>* Other names: IN-C005;|
| Experimental: Group C<br>IN-C005 dose C | Drug: IN-C005 dose C<br>* One time dose of IN-C005 dose C taken orally.<br>* Other names: IN-C005;|
| Experimental: Group D<br>IN-C005 dose D | Drug: IN-C005 dose D<br>* Oral administration of IN-C005 dose D once daily for 7 days.<br>* Other names: IN-C005;|
| Experimental: Group E<br>IN-C005 dose E | Drug: IN-C005 dose E<br>* Oral administration of IN-C005 dose E once daily for 7 days.<br>* Other names: IN-C005;|
| Experimental: Group F<br>IN-C005 dose F | Drug: IN-C005 dose F<br>* Oral administration of IN-C005 dose F once daily for 7 days.<br>* Other names: IN-C005;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Evaluation [Single Dosing Group (Korean Subjects), Multiple Dosing Group (Caucasian Subjects)] | Cmax of IN-C005 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Single Dosing Group (Korean Subjects), Multiple Dosing Group (Caucasian Subjects)] | AUClast of IN-C005 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Cmax,ss of IN-C005 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | AUCtau,ss of IN-C005 | Up to 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Evaluation [Single Dosing Group (Korean Subjects)] | AUClast of M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Single Dosing Group (Korean Subjects)] | Cmax of M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Single Dosing Group (Korean Subjects)] | AUCinf of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Single Dosing Group (Korean Subjects)] | Tmax of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Single Dosing Group (Korean Subjects)] | t½ of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Single Dosing Group (Korean Subjects)] | CL/F of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Single Dosing Group (Korean Subjects)] | Vd/F of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | AUClast of M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Cmax of M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Cmax,ss of M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | AUCinf of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | AUCtau,ss of M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Tmax of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Tmax,ss of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | t½ of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | CL/F of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Vd/F of IN-C005 and M1 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Cmin,ss of IN-C005 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Cav,ss of IN-C005 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | CLss/F of IN-C005 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Vss/F of IN-C005 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | PTF (peak to trough fluctuation) of IN-C005 | Up to 48 hours | 
| Pharmacokinetic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | R (accumulation ratio) of IN-C005 | Up to 48 hours | 
| Pharmacodynamic Evaluation [Single Dosing Group (Korean Subjects)] | Percent (%) duration of pH ≥ 4 in 24 hours | Pre-dose(0h) up to 24 hours after IP administration in each period | 
| Pharmacodynamic Evaluation [Single Dosing Group (Korean Subjects)] | Mean pH | Pre-dose(0h) up to 24 hours after IP administration in each period | 
| Pharmacodynamic Evaluation [Single Dosing Group (Korean Subjects)] | Median pH | Pre-dose(0h) up to 24 hours after IP administration in each period | 
| Pharmacodynamic Evaluation [Single Dosing Group (Korean Subjects)] | Change in pH from baseline to post-dose of Δduration % | Pre-dose(0h) up to 24 hours after IP administration in each period | 
| Pharmacodynamic Evaluation [Single Dosing Group (Korean Subjects)] | Change in pH from baseline to post-dose of Δmean pH | Pre-dose(0h) up to 24 hours after IP administration in each period | 
| Pharmacodynamic Evaluation [Single Dosing Group (Korean Subjects)] | Change in pH from baseline to post-dose of Δmedian pH | Pre-dose(0h) up to 24 hours after IP administration in each period | 
| Pharmacodynamic Evaluation [Single Dosing Group (Korean Subjects)] | AUEGlast(Area under the concentration-time curve of serum gastrin from time zero to the last point of quantifiable concentration) | Up to 48 hours | 
| Pharmacodynamic Evaluation [Single Dosing Group (Korean Subjects)] | Gmax (Maximum plasma concentration of gastrin) | Up to 48 hours | 
| Pharmacodynamic Evaluation [Single Dosing Group (Korean Subjects)] | Change in gastrin level from baseline to 1d and 7d of ΔAUEGlast | Up to 48 hours | 
| Pharmacodynamic Evaluation [Single Dosing Group (Korean Subjects)] | Change in gastrin level from baseline to 1d and 7d of ΔGmax | Up to 48 hours | 
| Pharmacodynamic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Percent (%) duration of pH ≥ 4 in 24 hours | Pre-dose(0h) up to 24 hours after IP administration in each period | 
| Pharmacodynamic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Mean pH | Pre-dose(0h) up to 24 hours after IP administration in each period | 
| Pharmacodynamic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Median pH | Pre-dose(0h) up to 24 hours after IP administration in each period | 
| Pharmacodynamic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | Change in pH from baseline to post-single dose and post-multiple dose (Δduration %, Δmean pH, Δmedian pH, etc) | Pre-dose(0h) up to 24 hours after IP administration in each period | 
| Pharmacodynamic Evaluation [Multiple Dosing Group (Caucasian Subjects)] | AUEGlast(Area under the concentration-time curve of serum gastrin from time zero to the last point of quantifiable concentration) | Up to 48 hours | 
| Pharmacodynamic Evaluation [Multiple Dosing Group (Caucasian Subjects] | Gmax (Maximum plasma concentration of gastrin) | Up to 48 hours | 
| Pharmacodynamic Evaluation [Multiple Dosing Group (Caucasian Subjects] | Change in gastrin level from baseline to 1d and 7d of ΔAUEGlast | Up to 48 hours | 
| Pharmacodynamic Evaluation [Multiple Dosing Group (Caucasian Subjects] | Change in gastrin level from baseline to 1d and 7d of ΔGmax | Up to 48 hours |