Clinical trial NCT02470286: A Phase 1 Clinical Study to Investigate the Pharmacokinetics and Safety/Tolerability of SA001 in Healthy Male Volunteers
Official title: A Phase1, Double-blind, Randomized, Placebo-control, Single Center, Single Dose Administration, Dose Escalation Study to Investigate the Pharmacokinetics, Safety and Tolerability of SA001 in Healthy Male Volunteers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Samjin Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2015-06-12
Enrollment: 40
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: 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.

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/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

Primary outcomes:
measure: The incidence of treated related adverse event
timeFrame: Part1: Day-2(administration) to approximately Day 15 (Post study visit)
Secondary outcomes:
measure: Area under the curve (AUC) from time 0 to the time of the last quantifiable concentration (AUC0-tlast) of SA001 and its metabolite
timeFrame: 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
measure: Area under the curve (AUC) from time 0 extrapolated to infinity (AUC0-∞) of SA001 and its metabolite
timeFrame: 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
measure: Maximum observed plasma concentration (Cmax) of SA001 and its metabolite
timeFrame: 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
measure: Time to reach the maximum observed plasma concentration (tmax) of SA001 and its metabolite
timeFrame: 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
measure: t1/2 of SA001 and its metabolite
timeFrame: 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
measure: CL/F of SA001 and its metabolite
timeFrame: 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
measure: Vz/F of SA001 and its metabolite
timeFrame: 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
measure: CLR of SA001 and its metabolite
timeFrame: 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
measure: Fraction recovered unchanged in urine (FR) of SA001 and its metabolite
timeFrame: 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
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University College of Medicine / Seoul National University Hospital
name: Kyung-sang Yu, M.D., Ph.D., M.B.A
role: PRINCIPAL_INVESTIGATOR
References: