Healthy
Conditions
Brief summary
The purpose of this phase1 study is to investigate the pharmacokinetics, safety and tolerability of a single oral dose of SA001 and its active metabolite in healthy male volunteers.
Detailed description
This study consists of Part 1 followed Part 2. Part 1 (Dose escalation study, SA001 60mg\ 300mg dose group) The part 1 is a dose escalation study. The starting dose is SA001 60mg, and the maximum dose is 300mg. 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 single oral administration on the fasting state. Part 2 (Single dose and food effect study, SA001 120mg and 300mg dose group) The purpose of this part 2 is to evaluate the food effect of a high-fat diets(HFDs) on the single oral dose pharmacokinetics of SA001 and its metabolite.
Interventions
DRUGSA001 60mg or Placebo
* Study Drug: SA001 60mg * Comparator: Placebo * Cohort 1 in the part 1 (Dose escalation study)
DRUGSA001 120mg or Placebo
* Study Drug: SA001 120mg * Comparator: Placebo * Cohort 2 in the part 1 (Dose escalation study) and part 2 (Food effect study)
DRUGSA001 180mg or Placebo
* Study Drug: SA001 180mg * Comparator: Placebo * Cohort 3 in the part 1 (Dose escalation study)
DRUGSA001 240mg or Placebo
* Study Drug: SA001 240mg * Comparator: Placebo * Cohort 4 in the part 1 (Dose escalation study)
DRUGSA001 300mg or Placebo
* Study Drug: SA001 300mg * Comparator: Placebo * Cohort 5 in the part 1(Dose escalation study) and part 2 (Food effect study)
Sponsors
Samjin Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
19 Years to 45 Years
Healthy volunteers
Yes
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/m\^2 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/1.73m\^2 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 prescription drug or herbal medicine within 14 days prior to the first administration of the Investigational product 12. 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 13. Subject who received other investigational products within 90 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of treated related adverse event | Part1: Day-2(administration) to approximately Day 15 (Post study visit) | Safety/Tolerability Assessment in the part 1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve (AUC) from time 0 extrapolated to infinity (AUC0-∞) of SA001 and its metabolite | Part1: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose, Part2: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose | — |
| Maximum observed plasma concentration (Cmax) of SA001 and its metabolite | Part1: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose, Part2: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose | — |
| Time to reach the maximum observed plasma concentration (tmax) of SA001 and its metabolite | Part1: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose, Part2: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose | — |
| t1/2 of SA001 and its metabolite | Part1: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose, Part2: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose | — |
| Area under the curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC0-tlast) of SA001 and its metabolite | Part1: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose, Part2: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose | — |
| Vz/F of SA001 and its metabolite | Part1: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose, Part2: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose | — |
| CLR of SA001 and its metabolite | Part1: predose and 0 ~ 4, 4 ~ 8, 8 ~ 12, 12 ~ 24, 24 ~ 32 and 32 ~ 48 hours postdose, Part2: predose and 0 ~ 4, 4 ~ 8, 8 ~ 12, 12 ~ 24, 24 ~ 32 and 32 ~ 48 hours postdose | CLR = Ae / AUCinf (Ae: total amount excreted in the urine) |
| Fraction recovered unchanged in urine (FR) of SA001 and its metabolite | Part1: predose and 0 ~ 4, 4 ~ 8, 8 ~ 12, 12 ~ 24, 24 ~ 32 and 32 ~ 48 hours postdose, Part2: predose and 0 ~ 4, 4 ~ 8, 8 ~ 12, 12 ~ 24, 24 ~ 32 and 32 ~ 48 hours postdose | — |
| CL/F of SA001 and its metabolite | Part1: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose, Part2: predose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 32, and 48 hours postdose | — |
Countries
South Korea
Outcome results
None listed