Clinical Study to Investigate the Pharmacokinetics and Safety/Tolerability of SA001 in Healthy Male Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: SA001 240mg + Rebamipide 200mg or Placebo; Drug: SA001 480mg or Placebo; Drug: SA001 710mg + Rebamipide 600mg or Placebo; Drug: SA001 1,080mg or Placebo; Drug: SA001 360mg or Placebo; Drug: SA001 720mg or Placebo

• Registration Number: NCT05303961
• Lead Sponsor: Samjin Pharmaceutical Co., Ltd.

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.

Study Timeline

• Study Start: 2016-06-07
• Primary Completion: 2016-11-11
• Study Completion: 2016-11-11
• Status Verified: 2022-03
• Study First Submitted: 2022-03-22
• Study First Submitted QC: 2022-03-22
• Last Update Submitted: 2022-03-22
• Study First Posted: 2022-03-31
• Last Update Posted: 2022-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 56

Inclusion Criteria

1. 19 years to 45 years (Healthy male Korean)
2. Body weight of 55 to 90kg; and BMI of 18.0 to 27.0 kg/m2
3. 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

1. 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.

2. 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

3. Subject with a history of clinically significant hypersensitivity or hypersensitivity reactions to drugs (aspirin, antibiotics, etc.)

4. Serum ALT(SGPT)/AST(SGOT) >1.5×institutional upper limit normal (ULN)

5. eGFR< 90mL/min/1.73m2

6. Systolic blood pressure <100 mmHg or >160 mmHg

7. Diastolic blood pressure <60 mmHg or >100 mmHg

8. Inadequate cardiac function confirmed by 12-lead ECG findings at screening as followings:

   • QTcF > 430msec (males)
   • PR interval > 200msec or < 110msec
   • QRS complex > 120msec
   • Evidence of 2nd- or 3rd-degree atrioventricular (AV) block
   • Pathologic Q waves (defined as Q-wave > 40msec or depth > 0.5mV)
   • Evidence of ventricular preexicitation, left bundle branch block (LBBB), right bundle branch block (RBBB, Incomplete RBBB)

9. Subject with risk factors for Torsade de pointes such as long QT syndrome, family history of sudden death, heart failure, hypokalemia, and arrhythmias

10. Subject with a history of drug abuse within 60 days prior to screening or who is positive for drugs of abuse in urine tests at screening

11. Subject who received any drugs such as

    • Prescription drug or herbal medicine within 14 days prior to the first administration of the investigational products
    • Over the counter (OTC) or vitamin within 7 days prior to the first administration of the investigational products

12. Subject who received other investigational products within 90 days prior to the first administration of the investigational products

13. Subject who have donated whole blood within 60 days prior to the first administration of the investigational products, or donated component blood or have received blood transfusion within 30 days prior to the first administration of the investigational products

14. Subject who continuously drink alcohol (more than 21 units/week, 1 unit = 10 g of pure alcohol) or cannot abstain from alcohol during the study period

15. Subject with history of smoking within 90 days prior to the first administration of the investigational products

16. Subject who cannot prohibit grapefruit/ caffeine-containing foods during the study period from 3 days before the first administration of the investigational products

17. Man of reproductive potential not willing to use contraceptive measures during the study period

18. Subject not eligible for study participation in the opinion of the investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Rebamipide	SA001 240mg + Rebamipide 200mg or Placebo	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.
Placebo	SA001 360mg or Placebo	Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
SA001	SA001 480mg or Placebo	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.
SA001	SA001 720mg or Placebo	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.
SA001	SA001 710mg + Rebamipide 600mg or Placebo	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.
Placebo	SA001 710mg + Rebamipide 600mg or Placebo	Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
SA001	SA001 240mg + Rebamipide 200mg or Placebo	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.
Placebo	SA001 720mg or Placebo	Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
SA001	SA001 1,080mg or Placebo	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.
SA001	SA001 360mg or Placebo	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.
Rebamipide	SA001 710mg + Rebamipide 600mg or Placebo	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.
Placebo	SA001 240mg + Rebamipide 200mg or Placebo	Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
Placebo	SA001 480mg or Placebo	Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.
Placebo	SA001 1,080mg or Placebo	Part 1: 8 subjects receiving a single dose of Placebo in the period 1. Part2: 6 subjects receiving multiple dose of Placebo.

Primary Outcome Measures

Name	Time	Method
Measure the Area Under the plasma concentration versus time Curve from the first sampled data extrapolated to infinity(AUCinf) of SA001 and Rebamipide	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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	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 Outcome Measures

Name	Time	Method
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)	Safety/Tolerability Assessment