Study To Evaluate the Safety, Tolerability, and Pharmacokinetics After Subcutaneous Administration of C1K in Healthy Subjects

Study Overview
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Brief Summary
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A dose-block randomized, double-blind, placebo-controlled, single and multiple ascending dose, first-in-human, phase 1 first in human clinical trial to evaluate the safety, tolerability, and pharmacokinetics after subcutaneous administration of C1K in healthy Korean subjects.

Official Title
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A Dose-block Randomized, Double-blind, Placebo-controlled, Single and Multiple Ascending Dose, First-in-human, Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics After Subcutaneous Administration of C1K in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: C1K 150mg
* Drug: C1K 300mg
* Drug: Placebo with the same volume of C1K 300mg
* Drug: C1K 600mg
* Drug: Placebo with the same volume of C1K 600mg
* Drug: C1K 900mg
* Drug: Placebo with the same volume of C1K 900mg
* Drug: C1K 1200mg
* Drug: Placebo with the same volume of C1K 1200mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subjects aged 19 - 45 years at the time of screening visit procedure. The subject weighs in the range of 50.0 - 90.0 kg and has a body mass index (BMI) in the range 18-27 kg/m2. Sufficient ability to understand the study after being informed about the study and provide written informed consent. Based on physical examination, vital sign, 12-lead ECG and laboratory test etc. and in the opinion of the investigator, the subject is suitable for the study. Exclusion Criteria: A subject with clinically significant hepatobiliary, renal, neurologic, respiratory, endocrine, blood•oncology, cardiovascular, urinary, or, psychical diseases or a history A subject who has difficulty with sub-cutaneous injection(ex: tattoo, allergy on skin etc.) A subject who has hypersensitivity to the drugs of the drugs containing the same class, or other drugs, or a history of clinically significant hypersensitivity A subject who has ventricular tachycardia, ventricular tachycardia, ventricular flutter or confirmed other ventricular flutter and QTc interval: > 450 ms or the other clinically significant medical findings A subject with the following results in the screening test: Blood AST (GOT), ALT (GPT): > Normal range upper × 1.5 Blood CPK > Normal range upper × 1.5 eGFR (CKD-EPI equation) < 60 mL/min/1.73 m2 Positive serological test (syphilis test, hepatitis B test, hepatitis C test, human immunodeficiency virus (HIV) test) A subject with the following results in the screening test: systolic blood pressure < 80 mmHg or > 140 mmHg diastolic blood pressure < 50 mmHg or > 90 mmHg A subject with a history of drug abuse or positive urine screening test for drug abuse A subject who administered any prescription drugs or herbal medicine within 2 weeks prior to the expected date of the first dose, or any over-the-counter drug (OTC drug) or vitamin within 1 week prior to the expected date of the first dose (However, can participate in the study if otherwise decided eligible by the investigator). A subject who participated in other clinical trial and administered investigational drug within 6 months prior to the expected date of the first dose A subject who donated whole blood within 2 months or the component blood within 1 month prior to the expected date of the first dose, or received blood transfusion within 1 month prior to the expected date of the first dose Smokers who smoke more than 10 cigarettes/day in the last 3 months as of screening day. A subject with persistent alcohol intake (> 21 units/week, 1 unit = 10 g of pure alcohol), or inability to abstain from drinking from 3 days before the expected date of the first dose until the last discharge A male subject who has plan to have a baby or to donate sperm. A female subject who is pregnant or lactating or has plan to lactate within 3 months after administration of IP A subject who is intending to become pregnant during this study or with inability to use a medically acceptable contraception method(ex. sterilization operation, intrauterine device etc. for Subject or subject's partner ※ medically acceptable contraception method Use of intrauterine device which is proven pregnancy failure rates in spouses (or partners). Use combined blocking contraceptives (for male or female) and antiseptic drugs Subject or partner's operation(vasectomized, bilateral tubal occlusion, hysterectomy) Subject who is considered inadequate to participation in the study due to other reason under investigator's discretion

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C1K 150mg<br>Subcutaneous Administration C1K 150mg single or multi dose | Drug: C1K 150mg<br>* Subcutaneously administrate C1K 150mg at Day 1, Day 8, Day 15<br>|
| Experimental: C1K 300mg or placebo<br>Subcutaneous Administration C1K 300mg or placebo single or multi dose | Drug: C1K 300mg<br>* Subcutaneously administrate C1K 300mg at Day 1, Day 8, Day 15<br>Drug: Placebo with the same volume of C1K 300mg<br>* Subcutaneously administrate placebo with the same volume of C1K 300mg at Day 1, Day 8, Day 15<br>|
| Experimental: C1K 600mg or placebo<br>Subcutaneous Administration C1K 600mg or placebo single or multi dose | Drug: C1K 600mg<br>* Subcutaneously administrate C1K 600mg at Day 1, Day 8, Day 15<br>Drug: Placebo with the same volume of C1K 600mg<br>* Subcutaneously administrate placebo with the same volume of C1K 600mg at Day 1, Day 8, Day 15<br>|
| Experimental: C1K 900mg or placebo<br>Subcutaneous Administration C1K 900mg or placebo single or multi dose | Drug: C1K 900mg<br>* Subcutaneously administrate C1K 900mg at Day 1, Day 8, Day 15<br>Drug: Placebo with the same volume of C1K 900mg<br>* Subcutaneously administrate placebo with the same volume of C1K 900mg at Day 1, Day 8, Day 15<br>|
| Experimental: C1K 1200mg or placebo<br>Subcutaneous Administration C1K 1200mg or placebo single or multi dose | Drug: C1K 1200mg<br>* Subcutaneously administrate C1K 1200mg at Day 1, Day 8, Day 15<br>Drug: Placebo with the same volume of C1K 1200mg<br>* Subcutaneously administrate placebo with the same volume of C1K 1200mg at Day 1, Day 8, Day 15<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability Assessment | Percentage of occurrences observed Adverse Event in each group. | Day -1 to Day 23 | 
| Safety and Tolerability Assessment by Value Changes in Vital Signs | Vital Signs including blood pressure and heart rate changes from baseline. | Day -1 to Day 23 | 
| Safety and Tolerability Assessment by Value Changes in Physical Examination | physical examination changes from baseline. | Day -1 to Day 23 | 
| Safety and Tolerability Assessment by Value Changes in Laboratory Test | laboratory test changes from baseline assessed through hematology, blood biochemistry, urinalysis and blood coagulation. | Day -1 to Day 23 | 
| Safety and Tolerability Assessment by Value Changes in 12-Lead Electrocardiogram | 12-Lead Electrocardiogram(ECG) changes from baseline. | Day -1 to Day 23 | 
| Safety and Tolerability Assessment by Response Change of Injection site. | Percentage of occurrences observed response change of injection site. | Day 1 to Day 23 | 
| Pharmacokinetic Assessment by Maximum concentration of C1K in plasma | Maximum concentration of C1K in plasma (Cmax) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 | 
| Pharmacokinetic Assessment by Area Under the Plasma Concentration-Time Curve of C1K from Time Zero to the Last Measurable Point | Area under the plasma C1K concentration-time curve from 0 to last(AUClast) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 | 
| Pharmacokinetic Assessment by Area under the plasma C1K concentration-time curve from 0 to infinity | Area under the plasma C1K concentration-time curve from 0 to last(AUCinf) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 | 
| Pharmacokinetic Assessment by The time of peak concentration of C1K | The time of peak concentration(Tmax) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 | 
| Pharmacokinetic Assessment by Elimination half-life of C1K | Elimination half-life(t1/2) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 | 
| Pharmacokinetic Assessment by Apparent Clearance of C1K | Apparent Clearance(CL/F) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 | 
| Pharmacokinetic Assessment by Apparent Volume of Distribution After extravascular administration of C1K | Apparent Volume of Distribution After extravascular administration(Vz/F) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 | 
| Pharmacokinetic Assessment by Accumulation Ratio of C1K | Accumulation Ratio(Rac) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 | 
| Pharmacokinetic Assessment by Minimum concentration of C1K in plasma | Minimum concentration of C1K in plasma(Cmin,ss) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 | 
| Pharmacokinetic Assessment by Average concentration of C1K in plasma | Average concentration of C1K in plasma(Cav) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 | 
| Pharmacokinetic Assessment by Peak to trough fluctuation ratio | Peak to trough fluctuation ratio(PTF) | Day 1/ Day 15 pre-dose(0 hour), 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hour at Day 1 and Day 15 |