Anti-Bacterial Agents, Healthy Volunteers, Methicillin-Resistant Staphylococcus Aureus
Conditions
Keywords
N-Rephasin® SAL200, endolysin, Placebo
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.
Interventions
BIOLOGICALN-Rephasin® SAL200
continuous intravenous infusion over 60 minutes
OTHERINT200-Placebo
Formulation buffer for continuous intravenous infusion over 60 minutes
Sponsors
Intron Biotechnology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Up to 50 days after administration |
Other
| Measure | Time frame |
|---|---|
| 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)] | Day 1 to 2 |
| Pharmacokinetic Parameters After Single IV Administration of N-Rephasin® SAL200 [Effective t1/2 (h)] | 0, 4, 8, 12, 16, 20, 24 hours post-dose |
| Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | up to 2hours |
| Pharmacokinetic Evaluation of N-Rephasin® SAL200 at the Administered Doses by Analysis of Concentration of N-Rephasin® SAL200 in Serum [Cmax (µg/ml)] | Day 1 to 2 |
| 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)] | Day 1 to 2 |
Countries
South Korea
Participant flow
Recruitment details
Enrollment have completed in a single center (Seoul National University Hospital) from Nov. 2013 and the completion date is Feb. 2014.
Pre-assignment details
57 subjects were screened and 36 subjects met the eligibility criteria.
Participants by arm
| Arm | Count |
|---|---|
| N-Rephasin® SAL200 0.1(mg/kg) N-Rephasin® SAL200, 0.1 mg/kg
N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes | 3 |
| N-Rephasin® SAL200 0.3(mg/kg) N-Rephasin® SAL200, 0.3 mg/kg
N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes | 6 |
| N-Rephasin® SAL200 1(mg/kg) N-Rephasin® SAL200,
1 mg/kg
N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes | 6 |
| N-Rephasin® SAL200 3(mg/kg) N-Rephasin® SAL200, 3 mg/kg
N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes | 6 |
| N-Rephasin® SAL200 10(mg/kg) N-Rephasin® SAL200, 10 mg/kg
N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes | 6 |
| INT200-Placebo Placebo
INT200-Placebo: Formulation buffer for continuous intravenous infusion over 60 minutes | 9 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | N-Rephasin® SAL200 0.1(mg/kg) | N-Rephasin® SAL200 0.3(mg/kg) | N-Rephasin® SAL200 1(mg/kg) | N-Rephasin® SAL200 3(mg/kg) | N-Rephasin® SAL200 10(mg/kg) | INT200-Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age, Customized | 25.3 Years | 27.8 Years | 29.8 Years | 23.7 Years | 30.5 Years | 26.2 Years | 27.4 Years |
| Body weight | 67.1 kg | 65.5 kg | 74.0 kg | 69.1 kg | 68.7 kg | 68.1 kg | 68.9 kg |
| Height | 176.8 cm | 171.3 cm | 175.1 cm | 174.8 cm | 170.5 cm | 174.5 cm | 173.6 cm |
| Race/Ethnicity, Customized Asian | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 36 Participants |
| Region of Enrollment South Korea | 3 participants | 6 participants | 6 participants | 6 participants | 6 participants | 9 participants | 36 participants |
| Sex/Gender, Customized Male | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 9 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 9 | 0 / 3 | 2 / 6 | 1 / 6 | 2 / 6 | 6 / 6 |
| serious Total, serious adverse events | 0 / 9 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers
Time frame: Up to 50 days after administration
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one drug-related AE | 1 Participants |
| Placebo | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one AE | 1 Participants |
| N-Rephasin® SAL200 (0.1 mg/kg) | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one AE | 0 Participants |
| N-Rephasin® SAL200 (0.1 mg/kg) | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one drug-related AE | 0 Participants |
| N-Rephasin® SAL200 (0.3 mg/kg) | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one AE | 2 Participants |
| N-Rephasin® SAL200 (0.3 mg/kg) | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one drug-related AE | 2 Participants |
| N-Rephasin® SAL200 (1 mg/kg) | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one AE | 1 Participants |
| N-Rephasin® SAL200 (1 mg/kg) | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one drug-related AE | 1 Participants |
| N-Rephasin® SAL200 (3 mg/kg) | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one AE | 2 Participants |
| N-Rephasin® SAL200 (3 mg/kg) | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one drug-related AE | 0 Participants |
| N-Rephasin® SAL200 (10 mg/kg) | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one AE | 6 Participants |
| N-Rephasin® SAL200 (10 mg/kg) | Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers | Number of Subjects with at least one drug-related AE | 6 Participants |
Other Pre-specified
Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration
Time frame: up to 2hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 0h | 0 μg/mL | Standard Deviation 0 |
| Placebo | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 1h | 0 μg/mL | Standard Deviation 0 |
| Placebo | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 1.5h | 0 μg/mL | Standard Deviation 0 |
| Placebo | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 2h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (0.1 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 0h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (0.1 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 2h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (0.1 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 1h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (0.1 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 1.5h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (0.3 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 2h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (0.3 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 1h | 0.13 μg/mL | Standard Deviation 0.05 |
| N-Rephasin® SAL200 (0.3 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 1.5h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (0.3 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 0h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (1 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 0h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (1 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 1h | 0.22 μg/mL | Standard Deviation 0.1 |
| N-Rephasin® SAL200 (1 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 2h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (1 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 1.5h | 0 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (3 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 2h | 0.04 μg/mL | Standard Deviation 0.05 |
| N-Rephasin® SAL200 (3 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 1.5h | 0.15 μg/mL | Standard Deviation 0.06 |
| N-Rephasin® SAL200 (3 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 1h | 0.40 μg/mL | Standard Deviation 0.13 |
| N-Rephasin® SAL200 (3 mg/kg) | Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration | 0h | 0 μg/mL | Standard Deviation 0 |
Other Pre-specified
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)]
Time frame: Day 1 to 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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)] | 0.03 µg*h/ml | Standard Deviation 0.005 |
| N-Rephasin® SAL200 (0.1 mg/kg) | 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)] | 0.05 µg*h/ml | Standard Deviation 0.02 |
| N-Rephasin® SAL200 (0.3 mg/kg) | 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)] | 0.57 µg*h/ml | Standard Deviation 0.31 |
| N-Rephasin® SAL200 (1 mg/kg) | 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)] | 7.26 µg*h/ml | Standard Deviation 3.42 |
| N-Rephasin® SAL200 (3 mg/kg) | 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)] | 59.79 µg*h/ml | Standard Deviation 9.03 |
Other Pre-specified
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)]
Time frame: Day 1 to 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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)] | 0.01 µg/ml/mg | Standard Deviation 0.001 |
| N-Rephasin® SAL200 (0.1 mg/kg) | 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)] | 0.005 µg/ml/mg | Standard Deviation 0.001 |
| N-Rephasin® SAL200 (0.3 mg/kg) | 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)] | 0.01 µg/ml/mg | Standard Deviation 0.01 |
| N-Rephasin® SAL200 (1 mg/kg) | 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)] | 0.03 µg/ml/mg | Standard Deviation 0.02 |
| N-Rephasin® SAL200 (3 mg/kg) | 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)] | 0.08 µg/ml/mg | Standard Deviation 0.01 |
Other Pre-specified
Pharmacokinetic Evaluation of N-Rephasin® SAL200 at the Administered Doses by Analysis of Concentration of N-Rephasin® SAL200 in Serum [Cmax (µg/ml)]
Time frame: Day 1 to 2
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetic Evaluation of N-Rephasin® SAL200 at the Administered Doses by Analysis of Concentration of N-Rephasin® SAL200 in Serum [Cmax (µg/ml)] | 0.04 µg/ml | Standard Deviation 0.01 |
| N-Rephasin® SAL200 (0.1 mg/kg) | Pharmacokinetic Evaluation of N-Rephasin® SAL200 at the Administered Doses by Analysis of Concentration of N-Rephasin® SAL200 in Serum [Cmax (µg/ml)] | 0.09 µg/ml | Standard Deviation 0.04 |
| N-Rephasin® SAL200 (0.3 mg/kg) | Pharmacokinetic Evaluation of N-Rephasin® SAL200 at the Administered Doses by Analysis of Concentration of N-Rephasin® SAL200 in Serum [Cmax (µg/ml)] | 0.82 µg/ml | Standard Deviation 0.5 |
| N-Rephasin® SAL200 (1 mg/kg) | Pharmacokinetic Evaluation of N-Rephasin® SAL200 at the Administered Doses by Analysis of Concentration of N-Rephasin® SAL200 in Serum [Cmax (µg/ml)] | 7.10 µg/ml | Standard Deviation 5.39 |
| N-Rephasin® SAL200 (3 mg/kg) | Pharmacokinetic Evaluation of N-Rephasin® SAL200 at the Administered Doses by Analysis of Concentration of N-Rephasin® SAL200 in Serum [Cmax (µg/ml)] | 55.99 µg/ml | Standard Deviation 10.37 |
Other Pre-specified
Pharmacokinetic Parameters After Single IV Administration of N-Rephasin® SAL200 [Effective t1/2 (h)]
Time frame: 0, 4, 8, 12, 16, 20, 24 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetic Parameters After Single IV Administration of N-Rephasin® SAL200 [Effective t1/2 (h)] | 0.04 h | Standard Deviation 0.02 |
| N-Rephasin® SAL200 (0.1 mg/kg) | Pharmacokinetic Parameters After Single IV Administration of N-Rephasin® SAL200 [Effective t1/2 (h)] | 0.04 h | Standard Deviation 0.01 |
| N-Rephasin® SAL200 (0.3 mg/kg) | Pharmacokinetic Parameters After Single IV Administration of N-Rephasin® SAL200 [Effective t1/2 (h)] | 0.25 h | Standard Deviation 0.05 |
| N-Rephasin® SAL200 (1 mg/kg) | Pharmacokinetic Parameters After Single IV Administration of N-Rephasin® SAL200 [Effective t1/2 (h)] | 0.38 h | Standard Deviation 0.06 |
| N-Rephasin® SAL200 (3 mg/kg) | Pharmacokinetic Parameters After Single IV Administration of N-Rephasin® SAL200 [Effective t1/2 (h)] | 0.38 h | Standard Deviation 0.05 |