A Dose-block Randomized, Double-blind, Placebo/Active-controlled, Single/Multiple Dosing, Dose-escalation Phase I Clinical Trial to Investigate the Safety/Tolerability and Pharmacokinetics of SA001 After Oral Administration in Healthy Male Subjects
Overview
- Phase
- Phase 1
- Intervention
- SA001 240mg + Rebamipide 200mg or Placebo
- Conditions
- Healthy
- Sponsor
- Samjin Pharmaceutical Co., Ltd.
- Enrollment
- 56
- Primary Endpoint
- Measure the Area Under the plasma concentration versus time Curve from the first sampled data extrapolated to infinity(AUCinf) of SA001 and Rebamipide
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
This study consists of Part 1 followed Part 2.
Part 1 The purpose of this phase1 study is to investigate the pharmacokinetics, safety and tolerability of a single oral dose of SA001 and active comparator(Rebamipide) in healthy male volunteers.
Part 2 The purpose of this phase1 study is to investigate the pharmacokinetics, safety and tolerability of multiple oral dose of SA001 in healthy male volunteers.
Detailed Description
Part 1(Single dose, dose escalation study, SA001 240mg\~1,080mg dose group) The starting dose is SA001 240mg, and the maximum dose is 1,080mg. Each dose group is assigned to Experimental group (SA001 or SA001 + Active Comparator(Rebamipide)) or Placebo group in a ratio of 3:1. The pharmacokinetics, safety and tolerability of SA001 and its metabolite are investigated after a single oral administration. Part 2 (Multiple dose, dose escalation study, SA001 360mg\~1,080mg dose group) The starting dose is SA001 360mg, and the maximum dose is 1,080mg. Each dose group is assigned to SA001 or Placebo in a ratio of 3:1. The pharmacokinetics, safety and tolerability of SA001 and its metabolite are investigated after a multiple oral administration.
Investigators
Eligibility Criteria
Inclusion Criteria
- •19 years to 45 years (Healthy male Korean)
- •Body weight of 55 to 90kg; and BMI of 18.0 to 27.0 kg/m2
- •Subject who voluntarily agrees to participate in this study and has given a written informed consent, after fully understanding the detailed explanation of this study
Exclusion Criteria
- •Subject with a disease history of any clinically significant condition as below.
- •Liver, Kidney, nervous system, immune system, respiratory system, endocrine system, tumor, cardiovascular disease or mental illness (mood disorder or obsessive-compulsive disorder etc.) etc.
- •Subject with a history of gastrointestinal disease (Crohn's disease, ulcer, acute or chronic pancreatitis, etc.) or gastrointestinal surgery (except simple appendicectomy or hernia surgery) that may affect the absorption of the study drug
- •Subject with a history of clinically significant hypersensitivity or hypersensitivity reactions to drugs (aspirin, antibiotics, etc.)
- •Serum ALT(SGPT)/AST(SGOT) \>1.5×institutional upper limit normal (ULN)
- •eGFR\< 90mL/min/1.73m2
- •Systolic blood pressure \<100 mmHg or \>160 mmHg
- •Diastolic blood pressure \<60 mmHg or \>100 mmHg
- •Inadequate cardiac function confirmed by 12-lead ECG findings at screening as followings:
- •QTcF \> 430msec (males)
Arms & Interventions
SA001
Part 1: 24 subjects are assigned to single dose groups(240mg, 480mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1:1 and receiving each dose of SA001 in the period 1. Part2: 18 subjects are assinged to multiple dose groups(360mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1 and receiving each dose of SA001.
Intervention: SA001 240mg + Rebamipide 200mg or Placebo
SA001
Part 1: 24 subjects are assigned to single dose groups(240mg, 480mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1:1 and receiving each dose of SA001 in the period 1. Part2: 18 subjects are assinged to multiple dose groups(360mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1 and receiving each dose of SA001.
Intervention: SA001 480mg or Placebo
SA001
Part 1: 24 subjects are assigned to single dose groups(240mg, 480mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1:1 and receiving each dose of SA001 in the period 1. Part2: 18 subjects are assinged to multiple dose groups(360mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1 and receiving each dose of SA001.
Intervention: SA001 710mg + Rebamipide 600mg or Placebo
SA001
Part 1: 24 subjects are assigned to single dose groups(240mg, 480mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1:1 and receiving each dose of SA001 in the period 1. Part2: 18 subjects are assinged to multiple dose groups(360mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1 and receiving each dose of SA001.
Intervention: SA001 1,080mg or Placebo
SA001
Part 1: 24 subjects are assigned to single dose groups(240mg, 480mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1:1 and receiving each dose of SA001 in the period 1. Part2: 18 subjects are assinged to multiple dose groups(360mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1 and receiving each dose of SA001.
Intervention: SA001 360mg or Placebo
SA001
Part 1: 24 subjects are assigned to single dose groups(240mg, 480mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1:1 and receiving each dose of SA001 in the period 1. Part2: 18 subjects are assinged to multiple dose groups(360mg, 720mg, 1080mg of SA001) in a ratio of 1:1:1 and receiving each dose of SA001.
Intervention: SA001 720mg or Placebo
Rebamipide
Part 1: 12 subjects are assigned to single dose groups(200mg, 600mg of Rebamipide) in a ratio of 1:1 and receiving each dose of Rebamipide in the period 2.
Intervention: SA001 240mg + Rebamipide 200mg or Placebo
Rebamipide
Part 1: 12 subjects are assigned to single dose groups(200mg, 600mg of Rebamipide) in a ratio of 1:1 and receiving each dose of Rebamipide in the period 2.
Intervention: SA001 710mg + Rebamipide 600mg or Placebo
Placebo
Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
Intervention: SA001 240mg + Rebamipide 200mg or Placebo
Placebo
Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
Intervention: SA001 480mg or Placebo
Placebo
Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
Intervention: SA001 710mg + Rebamipide 600mg or Placebo
Placebo
Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
Intervention: SA001 1,080mg or Placebo
Placebo
Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
Intervention: SA001 360mg or Placebo
Placebo
Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
Intervention: SA001 720mg or Placebo
Outcomes
Primary Outcomes
Measure the Area Under the plasma concentration versus time Curve from the first sampled data extrapolated to infinity(AUCinf) of SA001 and Rebamipide
Time Frame: Part 1: Predose9Day 1 0hour, Day 15 0hour), Postdose(Day 1 0.25~48hours, Day 15 0.25~48hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the apparent total body clearance(CL/F) of SA001 and Rebamipide
Time Frame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0~48hours, Day 15 0~24hours)
Investigate the pharmacokinetic parameters by collecting urine before and during administration of the investigational product.
Measure the cumulative fraction excreted unchanged parent in urine(Fe) of SA001 and Rebamipide
Time Frame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0~48hours, Day 15 0~24hours)
Investigate the pharmacokinetic parameters by collecting urine before and during administration of the investigational product.
Measure the Time to peak drug concentration at steady state(Tmax,ss) of SA001
Time Frame: Part 2: Predose(Day 1 0, 12hour, Day 2 0hour, Day 5 0hour, Day 7 12hour, Day 8 0, 12hour), Postdose(Day 1 0.25~8hours, Day 8 0.25~8hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the Area Under the plasma concentration versus time Curve from the first observed to last(AUClast) of SA001 and Rebamipide
Time Frame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0.25~48hours, Day 15 0.25~48hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the Time to peak drug concentration(Tmax) of SA001 and Rebamipide
Time Frame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0.25~48hours, Day 15 0.25~48hours)
Investigate the pharmacokinetic parameters by collecting blood and urine before and during administration of the investigational product.
Measure the Half Life(t1/2) of SA001 and Rebamipide
Time Frame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0.25~48hours, Day 15 0.25~48hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the apparent volume of distribution(Vz/F) of SA001 and Rebamipide
Time Frame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0~48hours, Day 15 0~24hours)
Investigate the pharmacokinetic parameters by collecting urine before and during administration of the investigational product.
Measure the Trough Drug Concentration at steady state(Cmin,ss) of SA001
Time Frame: Part 2: Predose(Day 1 0, 12hour, Day 2 0hour, Day 5 0hour, Day 7 12hour, Day 8 0, 12hour), Postdose(Day 1 0.25~8hours, Day 8 0.25~8hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the Peak Plasma Concentration (Cmax) of SA001 and Rebamipide
Time Frame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0.25~48hours, Day 15 0.25~48hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the Renal Clearance(CLr) of SA001 and Rebamipide
Time Frame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0~48hours, Day 15 0~24hours)
Investigate the pharmacokinetic parameters by collecting urine before and during administration of the investigational product.
Measure the Peak Plasma Concentration at steady state(Cmax,ss) of SA001
Time Frame: Part 2: Predose(Day 1 0, 12hour, Day 2 0hour, Day 5 0hour, Day 7 12hour, Day 8 0, 12hour), Postdose(Day 1 0.25~8hours, Day 8 0.25~8hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the average drug concentration in plasma during a dosing interval at steady state(Cav,ss) of SA001
Time Frame: Part 2: Predose(Day 1 0, 12hour, Day 2 0hour, Day 5 0hour, Day 7 12hour, Day 8 0, 12hour), Postdose(Day 1 0.25~8hours, Day 8 0.25~8hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the area under the plasma concentration-time curve for dosing interval(AUCτ) of SA001
Time Frame: Part 2: Predose(Day 1 0, 12hour, Day 2 0hour, Day 5 0hour, Day 7 12hour, Day 8 0, 12hour), Postdose(Day 1 0.25~8hours, Day 8 0.25~8hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the Half Life(t1/2) of SA001
Time Frame: Part 2: Predose(Day 1 0, 12hour, Day 2 0hour, Day 5 0hour, Day 7 12hour, Day 8 0, 12hour), Postdose(Day 1 0.25~8hours, Day 8 0.25~8hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the apparent total body clearance(CL/F) of SA001
Time Frame: Part 2: Predose(Day 1 0hour, Day 8 0hour, Day 16 0hour), Postdose(Day 1 0~24hours, Day 8 0~24hours, Day 16 0~24hours, Day 17 0~24hours)
Investigate the pharmacokinetic parameters by collecting urine before and during administration of the investigational product.
Measure the Peak-trough Fluctuation (PTF) of SA001
Time Frame: Part 2: Predose(Day 1 0, 12hour, Day 2 0hour, Day 5 0hour, Day 7 12hour, Day 8 0, 12hour), Postdose(Day 1 0.25~8hours, Day 8 0.25~8hours)
Investigate the pharmacokinetic parameters by collecting blood before and during administration of the investigational product.
Measure the Fraction recovered unchanged in urine (FR) of SA001
Time Frame: Part 2: Predose(Day 1 0hour, Day 8 0hour, Day 16 0hour), Postdose(Day 1 0~24hours, Day 8 0~24hours, Day 16 0~24hours, Day 17 0~24hours)
Investigate the pharmacokinetic parameters by collecting urine before and during administration of the investigational product.
Measure the Renal Clearance(CLr) of SA001
Time Frame: Part 2: Predose(Day 1 0hour, Day 8 0hour, Day 16 0hour), Postdose(Day 1 0~24hours, Day 8 0~24hours, Day 16 0~24hours, Day 17 0~24hours)
Investigate the pharmacokinetic parameters by collecting urine before and during administration of the investigational product.
Secondary Outcomes
- Incidence of Adverse Event(AE)(Part 1: Day-1(before the administration) to approximately Day 24 (Post study Visit) / Part 2: Day-1(before the administration) to approximately Day 29 (Post study Visit))