Anti-Bacterial Agents, Healthy Volunteers, Methicillin-Resistant Staphylococcus Aureus, Methicillin-Sensitive Staphylococcus Aureus Infection
Conditions
Keywords
Methicillin-Resistant Staphylococcus Aureus, Methicillin-Sensitive Staphylococcus Aureus, N-Rephasin SAL200
Brief summary
To evaluate the safety, pharmacokinetics, pharmacodynamics and immunogenicity of N-Rephasin® SAL200 following single and multiple ascending doses in healthy male volunteers after continuous intravenous infusion over 60 minutes.
Detailed description
* Forty subjects will be randomly assigned to receive either N-Rephasin® SAL200 injection or a placebo administered by a 60-min intravenous infusion. Within each group, 8 subjects (6 active and 2 placebo) will receive a single dose of 6 mg/kg, followed by multiple ascending dose of 3, 6, 9, and 12 mg/kg/day. The clinical trial will be performed in sequence from the lowest level, and the progress of the next dose level will be determined based on the safety results in the previous dose level. * Examinations by interview, physical examinations, and screening tests such as clinical laboratory tests and allergenicity will be conducted in volunteers within 4 weeks (-28\ -2d) from the previous day ot this clinical trial (-1d) to select subjects who are judged eligible for the study. * Eligible subjects will be called in the afternoon (-1d) to examine the allergenicity in the clinical center of Seoul National Unviersity Hospital. * Allergen-free subjects will be hospitalized on -1d and assigned with each subject number. All subjects are advised to fast from 10:00 p.m. overnight to the next morning, except drinking water. In the morning (09:00 a.m.) on 1d, subjects in each group will be given N-Rephasin® SAL200 injection or a placebo administered by a 60-min intravenous infusion, After that, the clinical trial will be conducted according to the designated schedule. * All subjects receiving at least one dose will undergo a post-study visit test after a certain period of time. Immunogenicity testing will be performed until approximately 50 days after treatment.
Interventions
BIOLOGICALN-Rephasin® SAL200
continuous intravenous infusion over 60 minutes
OTHERINT200-Placebo
Formulation buffer except active ingredient 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 subjects aged between 20 and 45 years at screening * Those whose body weight is between 50kg and 90kg, and BMI is between 18.0 and 27.0 * Subjects who have fully understood this clinical trial via detailed explanation, are willing to voluntarily participate in this study, and agree to give written informed consent and to follow all of trial-related rules.
Exclusion criteria
* Those who have clinically significant liver, kidney, nervous system, endocrine system, respiratory system, hemato-oncology, cardiovascular system, mental diseases or past history. * Those who have been diagnosed or suspected infectious disease within 30 days prior to the first dose of study medication * Those who have history of hypersensitivity to drugs containing N-Rephasin® SAL200 or other drugs (aspirin and antibiotics) * Those who have taken other drugs containing N-Rephasin® SAL200. * Those who are antibody-positive to N-Rephasin® SAL200 * Those who have SBP \<90mmHg or DBP \<50mmHg (otherwise SBP \> 150mmHg or DBP \> 100mmHg) in vital signs, when measured after a 3-minute rest in sitting position. * Those who have medical history of drug abuse or positive to urine drug screening * Has taken any prescription drugs or herbal medicines within 14 days prior to first dose of study medication; otherwise, has taken over-the-counter drugs or vitamins within 7 days prior to the first dose of study medication (However, if other conditions are appropriate upon judgment of the investigator, the subject may participate in this study.) * Those who has taken other study medications within 3 months prior to the study medication * Those who have donated whole blood within 2 months prior to the first dose of study medication or apheresis within 1 month, or received blood transfusion within 1 months prior to the first dose of study medication * Those who smoke cigarettes or are found to be nicotine metabolite-positive in urinalysis * Those who cannot continuously abstain from drinking alcohol (exceeding 21 units/week, 1 unit = 10g of pure alcohol) or smoking cigarettes during hospitalization * Those who are judged ineligible for the clinical study by the investigator due to other reasons, including the results of clinical laboratory tests * Those who do not agree to use medically accepted contraceptive measures for 60 days after the first dose of study medication, or those who are unwilling to report the partner's pregnancy until 90 days after the first dose of study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability Evaluation | Up to 50D (±2D) | Monitoring of adverse events (AEs) for Safety and Tolerability Evaluation |
Other
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamic Evaluation | Up to 2hours | Ex vivo antibacterial activity was assessed by bactericidal effects of the serum specimens collected from the trials were compared with calibration samples range of 0.05 to 1.0 μg/mL N-Rephasin®SAL200. |
| Immunogenicity Evaluation | Up to 50D (±2D) | Anti-drug antibody titer was assessed. |
| Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)] | Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose | Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200. |
| Pharmacokinetic Evaluation [Cmax (µg/mL)] | Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose | Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200. |
| Pharmacokinetic Evaluation [Vd (L)] | Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose | Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200. |
| Pharmacokinetic Evaluation [CL (L/h)] | Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose | Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200. |
| Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose | Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200 |
Countries
South Korea
Participant flow
Recruitment details
The recruitment was conducted in a single center (SEOUL NATIONAL UNIVERSITY HOSPITAL) from Feb. 2018 to Dec. 2018.
Pre-assignment details
59 subjects were screened and 33 subjects met inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| INT200-Placebo (Single Dose Study + Multi Dose Study) Saline
INT200-Placebo: Formulation buffer except active ingredient for continuous intravenous infusion over 60 minutes | 8 |
| N-Rephasin® SAL200 6mg/kg (Single Dose) Sigle dose N-Rephasin® SAL200 6mg/kg (single dose)
Experimental: N-Rephasin® SAL200
Active ingredient : SAL200 1ml (SAL-1 18 mg/mL) Manufacturer: BINEX Co., Ltd. (whole process contracted) Transparent and colorless vial filled with colorless clear liquid injection
continuous intravenous infusion over 60 minutes
Healthy Volunteers who were met eligibility criteria. | 6 |
| N-Rephasin® SAL200 1.5 mg/kg (3mg/kg/d), Multi Dose Multi dose Experimental: N-Rephasin® SAL200
Active ingredient : SAL200 1ml (SAL-1 18 mg/mL) Manufacturer: BINEX Co., Ltd. (whole process contracted) Transparent and colorless vial filled with colorless clear liquid injection
continuous intravenous infusion over 60 minutes
Healthy Volunteers who were met eligibility criteria. | 6 |
| N-Rephasin® SAL200 3mg/kg (6mg/kg/d), Multi Dose Multi dose Experimental: N-Rephasin® SAL200
Active ingredient : SAL200 1ml (SAL-1 18 mg/mL) Manufacturer: BINEX Co., Ltd. (whole process contracted) Transparent and colorless vial filled with colorless clear liquid injection
continuous intravenous infusion over 60 minutes
Healthy Volunteers who were met eligibility criteria. | 6 |
| N-Rephasin® SAL200 4.5mg/kg (9mg/kg/d), Multi Dose Multi dose Experimental: N-Rephasin® SAL200
Active ingredient : SAL200 1ml (SAL-1 18 mg/mL) Manufacturer: BINEX Co., Ltd. (whole process contracted) Transparent and colorless vial filled with colorless clear liquid injection
continuous intravenous infusion over 60 minutes
Healthy Volunteers who were met eligibility criteria. | 6 |
| Total | 32 |
Baseline characteristics
| Characteristic | INT200-Placebo (Single Dose Study + Multi Dose Study) | N-Rephasin® SAL200 6mg/kg (Single Dose) | N-Rephasin® SAL200 1.5 mg/kg (3mg/kg/d), Multi Dose | N-Rephasin® SAL200 3mg/kg (6mg/kg/d), Multi Dose | N-Rephasin® SAL200 4.5mg/kg (9mg/kg/d), Multi Dose | Total |
|---|---|---|---|---|---|---|
| Age, Customized Age | 29.0 years STANDARD_DEVIATION 5.6 | 28.5 years STANDARD_DEVIATION 6 | 33.5 years STANDARD_DEVIATION 6.2 | 31.3 years STANDARD_DEVIATION 5.8 | 29.2 years STANDARD_DEVIATION 4.9 | 30.2 years STANDARD_DEVIATION 5.6 |
| Height | 178.1 cm STANDARD_DEVIATION 6.2 | 175.0 cm STANDARD_DEVIATION 4.6 | 174.0 cm STANDARD_DEVIATION 3.6 | 174.5 cm STANDARD_DEVIATION 2.5 | 174.7 cm STANDARD_DEVIATION 4.9 | 175.4 cm STANDARD_DEVIATION 4.7 |
| Race/Ethnicity, Customized Asian | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 32 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 32 Participants |
| Weight | 77.2 kg STANDARD_DEVIATION 8.8 | 73.1 kg STANDARD_DEVIATION 5.5 | 70.3 kg STANDARD_DEVIATION 9.1 | 74.2 kg STANDARD_DEVIATION 5.9 | 69.1 kg STANDARD_DEVIATION 8.7 | 73.0 kg STANDARD_DEVIATION 7.9 |
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 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 1 / 2 | 6 / 6 | 1 / 6 | 3 / 6 | 1 / 6 | 3 / 6 |
| serious Total, serious adverse events | 0 / 2 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Safety and Tolerability Evaluation
Monitoring of adverse events (AEs) for Safety and Tolerability Evaluation
Time frame: Up to 50D (±2D)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo, Single Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Drug-Related TEAEs | 0 Participants |
| Placebo, Single Dose Study | Safety and Tolerability Evaluation | No. of Subjects with TEAEs | 1 Participants |
| Placebo, Single Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Serious TEAEs | 0 Participants |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Drug-Related TEAEs | 5 Participants |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Safety and Tolerability Evaluation | No. of Subjects with TEAEs | 6 Participants |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Serious TEAEs | 0 Participants |
| Placebo , Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Drug-Related TEAEs | 0 Participants |
| Placebo , Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with TEAEs | 1 Participants |
| Placebo , Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Serious TEAEs | 0 Participants |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Drug-Related TEAEs | 3 Participants |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with TEAEs | 3 Participants |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Serious TEAEs | 0 Participants |
| N-Rephasin® SAL200 (3 mg/kg), Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Drug-Related TEAEs | 1 Participants |
| N-Rephasin® SAL200 (3 mg/kg), Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with TEAEs | 1 Participants |
| N-Rephasin® SAL200 (3 mg/kg), Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Serious TEAEs | 0 Participants |
| N-Rephasin® SAL200 (4.5 mg/kg), Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with TEAEs | 3 Participants |
| N-Rephasin® SAL200 (4.5 mg/kg), Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Serious TEAEs | 0 Participants |
| N-Rephasin® SAL200 (4.5 mg/kg), Multiple Dose Study | Safety and Tolerability Evaluation | No. of Subjects with Drug-Related TEAEs | 2 Participants |
Other Pre-specified
Immunogenicity Evaluation
Anti-drug antibody titer was assessed.
Time frame: Up to 50D (±2D)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo, Single Dose Study | Immunogenicity Evaluation | ADA positive post baseline (regardless of baseline) | 0 Participants |
| Placebo, Single Dose Study | Immunogenicity Evaluation | ADA present at baseline | 0 Participants |
| Placebo, Single Dose Study | Immunogenicity Evaluation | ADA negative at baseline | 8 Participants |
| Placebo, Single Dose Study | Immunogenicity Evaluation | ADA positive post baseline (baseline negative) | 0 Participants |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Immunogenicity Evaluation | ADA negative at baseline | 6 Participants |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Immunogenicity Evaluation | ADA present at baseline | 0 Participants |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Immunogenicity Evaluation | ADA positive post baseline (regardless of baseline) | 4 Participants |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Immunogenicity Evaluation | ADA positive post baseline (baseline negative) | 4 Participants |
| Placebo , Multiple Dose Study | Immunogenicity Evaluation | ADA present at baseline | 0 Participants |
| Placebo , Multiple Dose Study | Immunogenicity Evaluation | ADA positive post baseline (baseline negative) | 2 Participants |
| Placebo , Multiple Dose Study | Immunogenicity Evaluation | ADA negative at baseline | 6 Participants |
| Placebo , Multiple Dose Study | Immunogenicity Evaluation | ADA positive post baseline (regardless of baseline) | 2 Participants |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Immunogenicity Evaluation | ADA present at baseline | 0 Participants |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Immunogenicity Evaluation | ADA positive post baseline (baseline negative) | 1 Participants |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Immunogenicity Evaluation | ADA positive post baseline (regardless of baseline) | 1 Participants |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Immunogenicity Evaluation | ADA negative at baseline | 6 Participants |
| N-Rephasin® SAL200 (3 mg/kg), Multiple Dose Study | Immunogenicity Evaluation | ADA negative at baseline | 5 Participants |
| N-Rephasin® SAL200 (3 mg/kg), Multiple Dose Study | Immunogenicity Evaluation | ADA present at baseline | 0 Participants |
| N-Rephasin® SAL200 (3 mg/kg), Multiple Dose Study | Immunogenicity Evaluation | ADA positive post baseline (baseline negative) | 1 Participants |
| N-Rephasin® SAL200 (3 mg/kg), Multiple Dose Study | Immunogenicity Evaluation | ADA positive post baseline (regardless of baseline) | 1 Participants |
Other Pre-specified
Pharmacodynamic Evaluation
Ex vivo antibacterial activity was assessed by bactericidal effects of the serum specimens collected from the trials were compared with calibration samples range of 0.05 to 1.0 μg/mL N-Rephasin®SAL200.
Time frame: Up to 2hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Single Dose Study | Pharmacodynamic Evaluation | 1.5h Mean concentration of bactericidal activity (μg/mL) | 0.38 μg/mL | Standard Deviation 0.24 |
| Placebo, Single Dose Study | Pharmacodynamic Evaluation | 2h Mean concentration of bactericidal activity (μg/mL) | 0.12 μg/mL | Standard Deviation 0.07 |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Pharmacodynamic Evaluation | 2h Mean concentration of bactericidal activity (μg/mL) | 0.02 μg/mL | Standard Deviation 0.03 |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Pharmacodynamic Evaluation | 1.5h Mean concentration of bactericidal activity (μg/mL) | 0.14 μg/mL | Standard Deviation 0.2 |
| Placebo , Multiple Dose Study | Pharmacodynamic Evaluation | 1.5h Mean concentration of bactericidal activity (μg/mL) | 0.22 μg/mL | Standard Deviation 0.1 |
| Placebo , Multiple Dose Study | Pharmacodynamic Evaluation | 2h Mean concentration of bactericidal activity (μg/mL) | 0.07 μg/mL | Standard Deviation 0.07 |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Pharmacodynamic Evaluation | 1.5h Mean concentration of bactericidal activity (μg/mL) | 0.20 μg/mL | Standard Deviation 0 |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Pharmacodynamic Evaluation | 2h Mean concentration of bactericidal activity (μg/mL) | 0.08 μg/mL | Standard Deviation 0.07 |
Other Pre-specified
Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)]
Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.
Time frame: Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Single Dose Study | Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)] | AUC last | 24.6 µg*h/mL | Standard Deviation 7.04 |
| Placebo, Single Dose Study | Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)] | AUC inf | 24.8 µg*h/mL | Standard Deviation 7.05 |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)] | AUC inf | 1.14 µg*h/mL | Standard Deviation 0.519 |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)] | AUC last | 1.10 µg*h/mL | Standard Deviation 0.503 |
| Placebo , Multiple Dose Study | Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)] | AUC last | 5.65 µg*h/mL | Standard Deviation 1.33 |
| Placebo , Multiple Dose Study | Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)] | AUC inf | 5.70 µg*h/mL | Standard Deviation 1.35 |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)] | AUC last | 11.3 µg*h/mL | Standard Deviation 1.37 |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Pharmacokinetic Evaluation [AUClast, AUCinf (µg*h/mL)] | AUC inf | 11.8 µg*h/mL | Standard Deviation 1.15 |
Other Pre-specified
Pharmacokinetic Evaluation [CL (L/h)]
Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.
Time frame: Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Single Dose Study | Pharmacokinetic Evaluation [CL (L/h)] | 19.0 L/h | Standard Deviation 5.63 |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Pharmacokinetic Evaluation [CL (L/h)] | 107 L/h | Standard Deviation 47.1 |
| Placebo , Multiple Dose Study | Pharmacokinetic Evaluation [CL (L/h)] | 40.3 L/h | Standard Deviation 5.89 |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Pharmacokinetic Evaluation [CL (L/h)] | 27.4 L/h | Standard Deviation 2.96 |
Other Pre-specified
Pharmacokinetic Evaluation [Cmax (µg/mL)]
Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.
Time frame: Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Single Dose Study | Pharmacokinetic Evaluation [Cmax (µg/mL)] | 21.4 µg/mL | Standard Deviation 3.91 |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Pharmacokinetic Evaluation [Cmax (µg/mL)] | 1.24 µg/mL | Standard Deviation 0.509 |
| Placebo , Multiple Dose Study | Pharmacokinetic Evaluation [Cmax (µg/mL)] | 4.93 µg/mL | Standard Deviation 1.08 |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Pharmacokinetic Evaluation [Cmax (µg/mL)] | 10.8 µg/mL | Standard Deviation 1.53 |
Other Pre-specified
Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)]
Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200
Time frame: Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Single Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | Tmax (h) | 1.00 h | Standard Deviation 1 |
| Placebo, Single Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | T1/2 (h) | 3.38 h | Standard Deviation 3.4 |
| Placebo, Single Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | MRTinf (h) | 1.12 h | Standard Deviation 0.314 |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | MRTinf (h) | 0.656 h | Standard Deviation 0.076 |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | T1/2 (h) | 0.386 h | Standard Deviation 0.082 |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | Tmax (h) | 1.00 h | Standard Deviation 1 |
| Placebo , Multiple Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | Tmax (h) | 1.00 h | Standard Deviation 1 |
| Placebo , Multiple Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | T1/2 (h) | 0.726 h | Standard Deviation 0.214 |
| Placebo , Multiple Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | MRTinf (h) | 0.782 h | Standard Deviation 0.596 |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | MRTinf (h) | 0.760 h | Standard Deviation 0.0651 |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | T1/2 (h) | 1.16 h | Standard Deviation 0.294 |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Pharmacokinetic Evaluation [Tmax, T1/2, MRTinf (h)] | Tmax (h) | 1.00 h | Standard Deviation 1 |
Other Pre-specified
Pharmacokinetic Evaluation [Vd (L)]
Blood sampling for PK evaluation was performed at the following time points. Summary of PK parameters after single IV administration of N-Rephasin® SAL200.
Time frame: Single administration: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours post-dose Multiple administration: the above timepoints and 25, 36, 48, 49, 60, 72, 72.25, 72.5, 72.75, 73, 73.5, 74, 75, 76, 77, 78, 80, 82, 84, 96 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo, Single Dose Study | Pharmacokinetic Evaluation [Vd (L)] | 90.2 L | Standard Deviation 89.5 |
| N-Rephasin® SAL200 (6mg/kg), Single Dose Study | Pharmacokinetic Evaluation [Vd (L)] | 55.6 L | Standard Deviation 13 |
| Placebo , Multiple Dose Study | Pharmacokinetic Evaluation [Vd (L)] | 41.3 L | Standard Deviation 9.82 |
| N-Rephasin® SAL200 (1.5 mg/kg), Multiple Dose Study | Pharmacokinetic Evaluation [Vd (L)] | 46.4 L | Standard Deviation 15.3 |