A Randomized, Open-label, Multiple Dosing, Cross-over Phase 1 Clinical Trial to Evaluate Pharmacokinetics/Pharmacodynamics and Safety/Tolerability of IN-C005 and IN-A001 After Oral Administration in Healthy Caucasian Subjects
Overview
- Phase
- Phase 1
- Intervention
- IN-A001 Y mg
- Conditions
- Healthy
- Sponsor
- HK inno.N Corporation
- Enrollment
- 20
- Locations
- 2
- Primary Endpoint
- Cmax
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to evaluate pharmacokinetics/pharmacodynamics and safety/tolerability of IN-C005 and IN-A001 after oral administration in healthy Caucasian subjects.
Detailed Description
\[Part 1\] To evaluate the pharmacokinetic (PK)/pharmacodynamic (PD) profiles and safety/tolerability of 100 mg IN-C005 versus 100 mg IN-A001 after multiple oral dosing in healthy Caucasian subjects \[Part 2\] To evaluate the PK/PD profiles and safety/tolerability of 50 mg IN-C005 versus 75 mg IN-C005 after multiple oral dosing in healthy Caucasian subjects
Investigators
Eligibility Criteria
Inclusion Criteria
- •Is healthy Caucasian adult aged 19 to 50 years (inclusive) at the time of signing the informed consent form (ICF) (A Caucasian 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).
- •Has ≥ 18.0 and ≤ 30.0 kg/m2 of body mass index (BMI) with a body weight (BW) ≥ 55.0 kg at screening.
- •Has a negative result in serum Helicobacter pylori IgG antibody test.
- •Decides to participate voluntarily in the study after being fully informed of and understanding the study completely, and provides his/her written informed consent prior to screening procedure.
- •Is eligible for this study in the opinion of the investigator based on the results of physical examination, clinical laboratory tests, interview, etc.
Exclusion Criteria
- •Has a history or current evidence of clinically significant disorder of hepatic, renal, nervous, respiratory, endocrine, hemato-oncologic, cardiovascular, urinary, and/or psychiatric system.
- •Has a history or current evidence of gastrointestinal disease that may affect the safety and PD assessments 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).
- •Has a history or current evidence of clinically significant hypersensitivity to study drugs or any ingredient of proton pump inhibitors and other drugs (such as aspirin and antibiotics).
- •Has a positive result on serology tests (for hepatitis B, human immunodeficiency virus \[HIV\], and hepatitis C).
- •Has a blood level of total bilirubin, AST (GOT), or ALT (GPT) \> 1.5 X upper limit of normal (ULN) based on screening procedures including repeated ones.
- •Has a calculated eGFR per MDRD equation \< 60 mL/min/1.73 m2 based on screening procedures including repeated ones.
- •Has systolic blood pressure (SBP) of \< 90 mmHg or \> 140 mmHg, diastolic blood pressure (DBP) of \< 50 mmHg or \> 95 mmHg, or pulse rate (PR) 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.
- •Has an 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.
- •Has a history of drug abuse or has a positive response to drug abuse on urine drug screening test.
- •Has 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 is expected to receive such medication during the study (Note: a subject may participate in the study at the discretion of the investigator provided the subject meets all the other criteria).
Arms & Interventions
Treatment AB
Participants will be randomized to receive IN-C005 Y mg (Treatment A) and IN-A001 Y mg (Treatment B) sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
Intervention: IN-A001 Y mg
Treatment AB
Participants will be randomized to receive IN-C005 Y mg (Treatment A) and IN-A001 Y mg (Treatment B) sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
Intervention: IN-C005 Y mg
Treatment BA
Participants will be randomized to receive IN-A001 Y mg and IN-C005 Y mg sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
Intervention: IN-A001 Y mg
Treatment BA
Participants will be randomized to receive IN-A001 Y mg and IN-C005 Y mg sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
Intervention: IN-C005 Y mg
Treatment CD
Participants will be randomized to receive IN-C005 Z mg (Treatment C) and IN-C005 X mg (Treatment D) sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
Intervention: IN-C005 X mg
Treatment CD
Participants will be randomized to receive IN-C005 Z mg (Treatment C) and IN-C005 X mg (Treatment D) sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
Intervention: IN-C005 Z mg
Treatment DC
Participants will be randomized to receive IN-C005 X mg and IN-C005 Z mg sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
Intervention: IN-C005 X mg
Treatment DC
Participants will be randomized to receive IN-C005 X mg and IN-C005 Z mg sequentially in a two-period sequence. There will be a washout period of at least 14 days between Period 1 and Period 2.
Intervention: IN-C005 Z mg
Outcomes
Primary Outcomes
Cmax
Time Frame: Day 1, Day 22
PK: Maximum concentration of drug in plasma
Change from baseline in percent duration of pH ≥4 in 24 hrs
Time Frame: Day 1, Day 7, Day 22, Day 28
PD: pH parameter
AUClast
Time Frame: Day 1, Day 22
PK: Area under the plasma drug concentration-time curve from 0 to last point of measurable concentration
AUCtau,ss
Time Frame: Day 7 and Day 28
PK: Area under the plasma drug concentration-time curve for a dosing interval at steady state
Cmax,ss
Time Frame: Day 7 and Day 28
PK: Maximum (peak) steady-state plasma drug concentration during a dosage interval
Percent duration of pH ≥4 in 24 hrs (duration %)
Time Frame: Day 7, Day 28
PD: pH parameter
Secondary Outcomes
- CL/F(Day 1, Day 22)
- Vd/F(Day 1, Day 22)
- t1/2,ss(Day 7, Day 28)
- Change from baseline in percent duration of pH ≥3 in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- AUCinf(Day 1, Day 22)
- Tmax(Day 1, Day 22)
- Tmax,ss(Day 7, Day 28)
- Cmin,ss(Day 7, Day 28)
- CLss/F(Day 7, Day 28)
- Gmax(Day 1, Day 7, Day 22, Day 28)
- t1/2(Day 1, Day 22)
- Cavg,ss(Day 7, Day 28)
- Vd,ss/F(Day 7, Day 28)
- PTF(Day 7, Day 28)
- R(Day 7, Day 28)
- Percent duration of pH ≥6 in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- Mean and median pH in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- Percent duration of pH ≥3 in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- Change from baseline in percent duration of pH ≥6 in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- Change from baseline in median pH in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- Change from baseline in mean pH in 24 hrs(Day 1, Day 7, Day 22, Day 28)
- AUEGlast(Day 1, Day 7, Day 22, Day 28)
- ΔAUEGlast(Day 1, Day 7, Day 22, Day 28)
- ΔGmax(Day 1, Day 7, Day 22, Day 28)