title: Pharmacokinetics and Tolerance of the Phage Endolysin-Based Candidate Drug SAL200 after a Single Intravenous Administration among Healthy Volunteers.
abstract: This study was a phase 1, single-center, randomized, double-blind, placebo-controlled, single-dosing, and dose-escalating study of intravenous SAL200. It is a new candidate drug for the treatment of antibiotic-resistant staphylococcal infections based on a recombinant form of the phage endolysin SAL-1. The study evaluated the pharmacokinetics, pharmacodynamics, and tolerance among healthy male volunteers after the intravenous infusion of single ascending doses of SAL200 (0.1, 0.3, 1, 3, and 10 mg/kg of body weight). SAL200 was well tolerated, and no serious adverse events (AEs) were observed in this clinical study. Most AEs were mild, self-limiting, and transient. The AEs reported in more than three participants were fatigue, rigors, headache, and myalgia. No clinically significant values with respect to the findings of clinical chemistry, hematology, and coagulation analyses, urinalysis, vital signs, and physical examinations were observed, and no notable trends in our electrocardiogram (ECG) results for any tested dose were noticed. A greater-than-dose-proportional increase with regard to systemic exposure and the maximum serum concentration was observed when the SAL200 dose was increased from 0.1 mg/kg to 10 mg/kg. This investigation constitutes the first-in-human phase 1 study of an intravenously administered, phage endolysin-based drug. (This study has been registered at ClinicalTrials.gov under identifier NCT01855048 and at the Clinical Research Information Service [https://cris.nih.go.kr/cris/] under identifier KCT0000968.).
authors.affiliation: iNtRON Biotechnology, Inc., Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Jun
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: In Jin
authors.initials: IJ
authors.lastname: Jang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Seonghae
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Kyungho
authors.initials: K
authors.lastname: Jang
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Kyung-Sang
authors.initials: KS
authors.lastname: Yu
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Moon-Woo
authors.initials: MW
authors.lastname: Seong
authors.affiliation: iNtRON Biotechnology, Inc., Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Gi Mo
authors.initials: GM
authors.lastname: Jung
authors.affiliation: iNtRON Biotechnology, Inc., Seongnam-si, Gyeonggi-do, Republic of Korea.
authors.forename: Seong Jun
authors.initials: SJ
authors.lastname: Yoon
authors.affiliation: iNtRON Biotechnology, Inc., Seongnam-si, Gyeonggi-do, Republic of Korea kangsh0403@naver.com.
authors.forename: Sang Hyeon
authors.initials: SH
authors.lastname: Kang
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004361:Drug Tolerance; D004562:Electrocardiography; D010450:Endopeptidases / Q000737:chemistry*; D064368:Healthy Volunteers; D006801:Humans; D013203:Staphylococcal Infections / Q000188:drug therapy; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D010450:Endopeptidases; C001143:endolysin
keywords: SAL200; phage endolysin; phase 1 clinical study; staphylococcal infections