Clinical trial NCT05303961: Clinical Study to Investigate the Pharmacokinetics and Safety/Tolerability of SA001 in Healthy Male Volunteers
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Samjin Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-03-31
Enrollment: 56
Sex: MALE
Minimum age (years): 19
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: Measure the Area Under the plasma concentration versus time Curve from the first observed to last(AUClast) of SA001 and Rebamipide
timeFrame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0.25~48hours, Day 15 0.25~48hours)
measure: Measure the Area Under the plasma concentration versus time Curve from the first sampled data extrapolated to infinity(AUCinf) of SA001 and Rebamipide
timeFrame: Part 1: Predose9Day 1 0hour, Day 15 0hour), Postdose(Day 1 0.25~48hours, Day 15 0.25~48hours)
measure: Measure the Peak Plasma Concentration (Cmax) of SA001 and Rebamipide
timeFrame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0.25~48hours, Day 15 0.25~48hours)
measure: Measure the Time to peak drug concentration(Tmax) of SA001 and Rebamipide
timeFrame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0.25~48hours, Day 15 0.25~48hours)
measure: Measure the Half Life(t1/2) of SA001 and Rebamipide
timeFrame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0.25~48hours, Day 15 0.25~48hours)
measure: Measure the apparent total body clearance(CL/F) of SA001 and Rebamipide
timeFrame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0~48hours, Day 15 0~24hours)
measure: Measure the apparent volume of distribution(Vz/F) of SA001 and Rebamipide
timeFrame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0~48hours, Day 15 0~24hours)
measure: Measure the Renal Clearance(CLr) of SA001 and Rebamipide
timeFrame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0~48hours, Day 15 0~24hours)
measure: Measure the cumulative fraction excreted unchanged parent in urine(Fe) of SA001 and Rebamipide
timeFrame: Part 1: Predose(Day 1 0hour, Day 15 0hour), Postdose(Day 1 0~48hours, Day 15 0~24hours)
measure: Measure the Trough Drug Concentration at steady state(Cmin,ss) of SA001
timeFrame: 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)
measure: Measure the Peak Plasma Concentration at steady state(Cmax,ss) of SA001
timeFrame: 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)
measure: Measure the average drug concentration in plasma during a dosing interval at steady state(Cav,ss) of SA001
timeFrame: 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)
measure: Measure the area under the plasma concentration-time curve for dosing interval(AUCτ) of SA001
timeFrame: 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)
measure: Measure the Time to peak drug concentration at steady state(Tmax,ss) of SA001
timeFrame: 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)
measure: Measure the Half Life(t1/2) of SA001
timeFrame: 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)
measure: Measure the Peak-trough Fluctuation (PTF) of SA001
timeFrame: 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)
measure: Measure the Fraction recovered unchanged in urine (FR) of SA001
timeFrame: 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)
measure: Measure the apparent total body clearance(CL/F) of SA001
timeFrame: 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)
measure: Measure the Renal Clearance(CLr) of SA001
timeFrame: 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)
Secondary outcomes:
measure: Incidence of Adverse Event(AE)
timeFrame: 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)
Other outcomes:
Locations:
Study officials:
References: