A Single Ascending Doses (SAD) of a Novel Engineered Cationic Peptide PLG0206 in Healthy Subjects.

INTERVENTION: Dose: Proposed dose escalation scheme 0.05, 0.125, 0.25, 0.5, 1, 2, and 3 mg/kg. Route of Administration: Intravenous infusion over 1 hour. There will be a minimum of 7 days between dose escalation within which the safety data will be evaluated at each dose level before escalation to the next dose level. Subjects will be randomized to PLG0206 IV or Placebo IV group in a 3:1 ratio There will be a total of up to 56 subjects, divided into up to 7 sequential groups: Within each group (n=8 subjects), 2 subjects will receive placebo and 6 will receive PLG0206. At each dose level, there will be 2 sentinel subjects, (1 active, 1 placebo), who will be dosed at least 48 hours in advance of the other subjects in their respective group. There will be at least 7 day period after dosing each of the dose levels before dose escalation. CONDITION: Infection ‐ Other infectious diseases Microbial Infections; ; Microbial Infections PRIMARY OUTCOME: Safety and Tolerability[Safety and Tolerability will be evaluated as follows: Blood samples for pharmacodynamic parameters and immunogenicity test will be obtained during the study. Blood samples will be collected to assay for PLG0206 at pre‐dose, 0.5 ‐h after start of infusion, within 1 minute after the end‐of‐infusion and at 0.5, 1, 2, 4, 6, 8, 12, 20, 24, 36 and 48 hours after the end‐of‐infusion. Total urine will be collected between the intervals 0‐8, 8‐16, 16‐24 and 24‐48 hours post dose. Vital signs will be recorded within 90 minutes pre‐dose and at 0.5, 1, 2, 3, 4, 6, 9, 12, 24 (Day 2) and 48 hours (prior to discharge on Day 3) post‐ start of the infusion, after at least 3 minutes of rest in supine position. A 12‐lead ECG will be performed on Day 1 (dosing day), within 15 minutes of infusion start and 15 minutes after it stops. Continuous cardiac monitoring (Holter), will be performed on Day ‐1 for 12 hours starting at 24 hours prior to the start of infusion on Day 1. It will begin again from the start of infusion up to 24 hours after infusion. The PK parameters which will be analysed are as follows but not limited to the following: ; Primary PK parameters: Cmax, AUC0‐t, AUC0‐Inf; Secondary PK parameters: Time Corresponding to Cmax (Tmax), Tlast, Terminal half‐life ( T1/2), Terminal elimination rate ( ?z), Apparent clearance (CL) and Apparent volume of distribution (Vz/F).; ] SECONDARY OUTCOME: To characterize the pharmacokinetic (PK) profile of single doses of PLG0206.[Pharmacokinetic profile will be analysed as follows: Blood samples for PK assessment will be collected to assay for PLG0206 at pre‐dose, 0.5 ‐h after start of infusion, within 1 minute after the end‐of‐infusion and at 0.5, 1, 2, 4, 6, 8, 12, 20, 24, 36 and 48 hours after the end‐of‐infusion. Batch Urine PK analysis will be performed, and samples will be collected at the following time points: 90 min prior to drug administration apart from urine PK samples which should be obtained 15 min prior to drug administration and between the intervals 0‐8, 8‐16, 16‐24 and 24‐48 hours post dose. The PK parameters which will be analysed are as follows but not limited to the following: ; Primary PK parameters: Cmax, AUC0‐t, AUC0‐Inf ; Secondary PK parameters: Time Corresponding to Cmax (Tmax), Tlast, Terminal half‐life ( T1/2), Terminal elimination rate ( ?z), Apparent clearance (CL) and Apparent volume of distribution (Vz/F). ; ] 2. Healthy with no clinically significant medical problems. 3. BMI between 18 and 30 kg/m2 with weight between 45 and 100 kg (both inclusive) at Day ‐1. INCLUSION CRITERIA: 1. Male or female between 18 and 45 years of age (inclusive). Females of child bearing potential using oral contraceptives who agree to use two reliable methods of contraception (e.g., double‐barrier condom plus diaphragm, condom or diaphragm along with stable dose of oral contraception) throughout the study perilod and until 3 months after receiving study drug. Women of childbearing potential will require compulsory pregnancy testing. A negative serum pregnancy test is required at screening, and a negative urine pregnancy test is required at Day ‐1 if Day ‐1 > 7 days from screening. 4. No history of alcohol or drug abuse (Barbiturates, Benzodiazepines, Cocaine, Methadone, Amphetamines, Methamphetamines, Opiates, Phencyclidine, Tetrahydrocannabinol (cannabis), Tricyclic Antidepressants). Subjects should