Clinical trial NCT02753504: Study to Investigate the Safety/Tolerability and Pharmacokinetics/Pharmacodynamics of CKD-519
Official title: A Dose-block Randomized, Double-blind, Placebo-controlled, Multiple Dosing, Dose-escalation Phase I Clinical Trial to Investigate the Safety/Tolerability and Pharmacokinetics/Pharmacodynamics of CKD-519 After Oral Administration in Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dyslipidemia
Keywords: Dyslipidemia
Lead sponsor: Chong Kun Dang Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2016-04-28
Enrollment: 24
Sex: ALL
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the safety/tolerability and pharmacokinetics/pharmacodynamics of CKD-519

Detailed description: A Dose-block Randomized, Double-blind, Placebo-controlled, Multiple Dosing, Dose-escalation Phase I Clinical Trial to Investigate the Safety/Tolerability and Pharmacokinetics/Pharmacodynamics of CKD-519 After Oral Administration in Healthy Adult Volunteers

Eligibility criteria: Inclusion Criteria:

1. Between 19 aged and 55 aged in healthy adult
2. Body weight more than 55kg in male, 50kg in female
3. Body Mass Index more than 18.5 and under 25(body mass index=kg/m2)
4. If female, must include more than one among the items

   * The menopause(there is no natural menses for at least 2 years)
   * Surgical Infertility(hysterectomy or bilateral oophorectomy, tubal ligation or other methods of infertility condition
5. If men has sexual life with women of childbearing age, Necessarily he agrees that use condoms and do not sperm donation until two months during clinical trials and after the final dosage of investigational products
6. Those who fully understand about this clinical trials after enough hearing, and then decided to join the clinical trials by themselves and to comply with the precautions written consent

Exclusion Criteria:

1. Have clinically significant disease that hepatobiliary system(severe hepatic impairment, etc), kidney(severe renal impairment, etc), nervous system, immune system, respiratory system, endocrine system, hemato-oncology disease, cardiovascular system(heart failure, etc) or mental illness, or a history of mental disease.
2. Have a history of Toresades de pointes(TdP) or additional risk factors for Toresades de pointes(TdP). (Family history of long QT syndrome or sudden death, heart failure, hypokalemia, etc)
3. Have a gastrointestinal disease history that can effect drug absorption(Crohn's disease, ulcers, etc.) or surgery(except simple appendectomy or hernia surgery)
4. Hypersensitivity reaction or clinically significant hypersensitivity reaction in the history of drugs or additives.
5. An impossible one who participates in clinical trial including screening tests(medical history taking, BP, 12-lead ECG, physical examination, blood\&urine laboratory test result) before 28 days the taking investigational Products.
6. Defined by the following laboratory parameters

   * AST, ALT\>1.25 upper limit of normal range
   * Total bilirubin\>1.5 upper limit of normal range
   * CPK\>1.5 upper limit of normal range
   * eGFR(using by MDRD method)\<60mL/min/1.73m2
7. Defined by the following 12-lead ECG

   * HR\<40 or \>110bpm
   * PR interval\>220ms or ≤110ms
   * QRS interval\>120ms
   * QTcF\<300ms or \>450ms
   * Pathologic Q-waves (defined as \>40ms or depth\>0.5mV)
   * Incomplete or complete bundle branch block
   * Pre-excitation (e.g., Wolfe-Parkinson-White Syndrome)
   * Atrial fibrillation/flutter
   * Second- or third-degree atrioventricular (AV)block
   * Investigator judges to be unfavorable for consistently accurate QT measurements(e.g., indistinct QRS onset, low amplitude T wave, inverted or terminally inverted T wave, merged T/U waves, indistinct T wave offset , or prominent U wave that affects QT measurement)
8. Sitting SBP\>150mmHg or \<90mmHg, sitting DBP\>100mmHg or \<50mmHg, after 5 minutes break.
9. Drug abuse or have a history of drug abuse showes a positive for urine drug test.
10. Pregnant or lactating women.
11. A heavy caffeine consumer(caffeine\>5 cups/day), alcohol consumer(alcohol\>210g/week), or smoker(cigarette\>10 cigarettes/day)
12. Subject takes ethical drug or herbal medicine within 14 days, OTC within 7 days before the beginning of study treatment but investigator determine that the taking drug affect this study or could affect the safety of subjects.
13. Subject who takes inhibitor and inducers of drug metabolizing enzyme(Barbiturates etc.) within 30 days.
14. Taking concomitant medications that prolong the QT/QTc interval within 14 days before the beginning of study treatment.
15. Taking foods containing grapefruit within 7 days before the beginning of study treatment(ex. Drinking containing grapefruit of 1L per a day or more within 7 days before the beginning of study treatment)
16. Subject who treated with any investigational drugs within 90 days before the beginning of study treatment
17. Previously donate whole blood within 60 days or component blood within 30 days.
18. An impossible one who participants in clinical trial by investigator's decision including laboratory test result or another reason.
19. Positive for Serology test(Hepatitis B, Hepatitis C, HIV)

Primary outcomes:
measure: Cmax,ss of CKD-519
timeFrame: Day1: 0(predose)~24 Day3~Day13: 0(predose) Day14: 0(predose)~168
measure: AUCt,ss of CKD-519
timeFrame: Day1: 0(predose)~24 Day3~Day13: 0(predose) Day14: 0(predose)~168
measure: AUCinf,ss of CKD-519
timeFrame: Day1: 0(predose)~24 Day3~Day13: 0(predose) Day14: 0(predose)~168
measure: Tmax,ss of CKD-519
timeFrame: Day1: 0(predose)~24 Day3~Day13: 0(predose) Day14: 0(predose)~168
measure: T1/2 of CKD-519
timeFrame: Day1: 0(predose)~24 Day3~Day13: 0(predose) Day14: 0(predose)~168
measure: Cmin,ss of CKD-519
timeFrame: Day1: 0(predose)~24 Day3~Day13: 0(predose) Day14: 0(predose)~168
measure: Cavg,ss of CKD-519
timeFrame: Day1: 0(predose)~24 Day3~Day13: 0(predose) Day14: 0(predose)~168
measure: CLss/F of CKD-519
timeFrame: Day1: 0(predose)~24 Day3~Day13: 0(predose) Day14: 0(predose)~168
measure: accumulation ratio(D14/D1: Cmax, AUC0-t) of CKD-519
timeFrame: Day1: 0(predose)~24 Day3~Day13: 0(predose) Day14: 0(predose)~168
Secondary outcomes:
measure: CETP activity of CKD-519
timeFrame: Day1: 0(predose)~24 Day3~Day13: 0(predose) Day14: 0(predose)~168
measure: CETP concentration of CKD-519
timeFrame: Day1, 2, 6, 10, 14: 0(predose) Day15, 16, 17: Day14(24, 48, 72)
measure: Lipid parameter(HDL-c, LDL-c, Total Cholesterol, Triglyceride) of CKD-519
timeFrame: Day1, 3, 7, 10, 12, 14: 0(predose) Day15, 16, 17, 21: Day14(24, 48, 72, 169)
measure: Lipid parameter(Apolipoprotein A-I, E, B) of CKD-519
timeFrame: Day1, 8: 0(predose) Day15: Day14(24)
measure: QT/QTc(QTcF, QTcB, QT, HR, RR, PR, QRS) of CKD-519
timeFrame: Baseline(Day-1): 0~12 Day1: 0~24 Day14: 0~24
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
state: Seodaemun-gu
Study officials:
affiliation: Severance Hospital
name: Min-Su Park, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: