Clinical trial NCT01855048: A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of N-Rephasin® SAL200 in Healthy Male Volunteers
Official title: A Randomized, Double-blind, Placebo-controlled, Clinical Study to Evaluate the Safety, Pharmacokinetics and Phyarmacodynamcs of a Single Intravenous Dose of N-Rephasin® SAL200, in Healthy Male Valunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Anti-Bacterial Agents
Methicillin-Resistant Staphylococcus Aureus
Keywords: N-Rephasin® SAL200
endolysin
Placebo
Lead sponsor: Intron Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-16
Enrollment: 36
Sex: MALE
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The Objectives of this study is to evaluate the safety, pharmacokinetics and pharmacodynamics of single dose of N-Rephasin® SAL200 in healthy male subjects.

Detailed description: The purposes of this study are to evaluate the pharmacokinetics, and pharmacodynamics and safety of an experimental intravenous medication, N-Rephasin® SAL200 in healthy male. Participants will include 36 male volunteers. Participants will be grouped according to dosage of N-Rephasin® SAL200 including placebo (0 mg/kg). Study procedures include: check of vital signs, reporting any experienced side effects, physical examination including assessment of the cardiovascular system, and blood sample collection for monitoring of pharmacokinetics, pharmacodynamics and antibody production etc. Participants will be involved in study related procedures for up to 50 days after injection.

Eligibility criteria: Inclusion Criteria:

* Healthy male subject whose age is 20 \~ 45 at the time of screening visit.
* Body weight of ≥50kg and \<90kg, while within ±20% of the ideal body weight. \[ideal body weight(kg) = {height(cm)-100}x 0.9\]
* Subject agreed to participate in the trial and to follow all of trial-related rules with a full understanding, after having a full account of the trial

Exclusion Criteria:

* Present disease(s) or medical history(ies) which is(are) clinically significant on liver, heart, nervous system, respiratory system, haemato-oncology, cardiovascular or psychopathy.
* Diagnosed or suspected infectious disease within 30 days in prior to the administration.
* Clinically significantly allergic to drug(s) containing AI of N-Rephasin® SAL200 or to other drugs including aspirin and antibiotics, or has medical history(ies) on such allergy.
* Already has taken other drug(s) containing AI of N-Rephasin® SAL200.
* Positive for Antibody of N-Rephasin® SAL200.
* SBP≤90mmHg or DBP≤50mmHg, otherwise, SBP≥150mmHg or DBP≥100mmHg in Vital sign which was measured after taking 3 minutes of resting in sitting position.
* Has medical history of drug abuse or positive to drug abuse in urine drug screening.
* Has taken any prescription drug(s) or herbal medicine(s) within 14 days prior to the administration, otherwise, any OTC(Over the counter) (s) or vitamin(s) within 7 days prior to the administration(However, can participate in the study if investigator makes a decision that the subject can participate regardless the drug taken).
* Has taken any other study drugs within 2 months prior to the administration.
* Has donated blood(whole blood donation or component transfusion) within (2 months or 1 month, respectively) in prior to the administration, otherwise, has received blood transfusion within 1 month in prior to the administration.
* Smoke at present or positive to metabolism of nicotine in urine test.
* Drink regularly(over 21 units/week, 1 unit= 10 g of pure alcohol), otherwise, is not able to interrupt drinking and smoking in study period.
* Investigator made a decision that the subject is not eligible based on results of laboratory test or other reason.
* Not agree with contraception for 60days after the administration, otherwise, notification of pregnancy in case of his partner is pregnant for 90 days after the administration.

Primary outcomes:
measure: Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers
timeFrame: Up to 50 days after administration
Secondary outcomes:
Other outcomes:
measure: Pharmacokinetic Parameters After Single IV Administration of N-Rephasin® SAL200 [Effective t1/2 (h)]
timeFrame: 0, 4, 8, 12, 16, 20, 24 hours post-dose
measure: Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration
timeFrame: up to 2hours
measure: Pharmacokinetic Evaluation of N-Rephasin® SAL200 at the Administered Doses by Analysis of Concentration of N-Rephasin® SAL200 in Serum [Cmax (µg/ml)]
timeFrame: Day 1 to 2
measure: Pharmacokinetic Evaluation of N-Rephasin® SAL200 at the Administered Doses by Analysis of Concentration of N-Rephasin® SAL200 in Serum [Cmax/D (µg/ml/mg)]
timeFrame: Day 1 to 2
measure: Pharmacokinetic Evaluation of N-Rephasin® SAL200 at the Administered Doses by Analysis of Concentration of N-Rephasin® SAL200 in Serum [AUC Last (µg*h/ml)]
timeFrame: Day 1 to 2
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Seoul National University Hospital
name: In Jin Jang, M.D., Ph. D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Loessner MJ. Bacteriophage endolysins--current state of research and applications. Curr Opin Microbiol. 2005 Aug;8(4):480-7. doi: 10.1016/j.mib.2005.06.002.
citation: Fischetti VA. Bacteriophage lysins as effective antibacterials. Curr Opin Microbiol. 2008 Oct;11(5):393-400. doi: 10.1016/j.mib.2008.09.012. Epub 2008 Oct 14.
citation: Loeffler JM, Nelson D, Fischetti VA. Rapid killing of Streptococcus pneumoniae with a bacteriophage cell wall hydrolase. Science. 2001 Dec 7;294(5549):2170-2. doi: 10.1126/science.1066869.
citation: Wu JA, Kusuma C, Mond JJ, Kokai-Kun JF. Lysostaphin disrupts Staphylococcus aureus and Staphylococcus epidermidis biofilms on artificial surfaces. Antimicrob Agents Chemother. 2003 Nov;47(11):3407-14. doi: 10.1128/AAC.47.11.3407-3414.2003.
citation: Schellekens H. Immunogenicity of therapeutic proteins. Nephrol Dial Transplant. 2003 Jul;18(7):1257-9. doi: 10.1093/ndt/gfg164. No abstract available.
citation: Jun SY, Jang IJ, Yoon S, Jang K, Yu KS, Cho JY, Seong MW, Jung GM, Yoon SJ, Kang SH. Pharmacokinetics and Tolerance of the Phage Endolysin-Based Candidate Drug SAL200 after a Single Intravenous Administration among Healthy Volunteers. Antimicrob Agents Chemother. 2017 May 24;61(6):e02629-16. doi: 10.1128/AAC.02629-16. Print 2017 Jun.