A Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of N-Rephasin® SAL200 in Healthy Male Volunteers

• Sponsor: Intron Biotechnology, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01855048
• Collaborator: (none)
• Enrollment: 36
• Location: 1
• Arms: 2
• Actual Duration (Months): 6.1
• Patients Per Site Per Month: 5.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers; Anti-Bacterial Agents; Methicillin-Resistant Staphylococcus Aureus	Biological: N-Rephasin® SAL200; Other: INT200-Placebo	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Aug 6, 2013
• Actual Primary Completion Date: Feb 7, 2014
• Actual Study Completion Date: Feb 7, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: N-Rephasin® SAL200 N-Rephasin® SAL200, 0.1 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg	Biological: N-Rephasin® SAL200; continuous intravenous infusion over 60 minutes
Placebo Comparator: INT200-Placebo Placebo	Other: INT200-Placebo; Formulation buffer for continuous intravenous infusion over 60 minutes

Outcome Measures

Primary Outcome Measures

1. Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers [Up to 50 days after administration]

Other Outcome Measures

1. Pharmacokinetic Parameters After Single IV Administration of N-Rephasin® SAL200 [Effective t1/2 (h)] [0, 4, 8, 12, 16, 20, 24 hours post-dose]

2. Pharmacodynamics Evaluation of N-Rephasin® SAL200 : Mean Concentration of Bactericidal Activity After Single Dose of N-Rephsin® SAL200 IV Administration [up to 2hours]

3. 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]

4. 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]

5. 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]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 45 Years
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Hospital	Seoul		Korea, Republic of	110-744

Sponsors and Collaborators

• Intron Biotechnology, Inc.

Investigators

• Principal Investigator: In Jin Jang, M.D., Ph. D., Seoul National University Hospital

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• FDA, Guidance for Industry, Estimating the Maximum Safe Starting Dose inInitial Clinical Trials for Therapeutics in Adult Healthy Volunteers, 2005.

Publications

None provided.

• Responsible Party: Intron Biotechnology, Inc.
• ClinicalTrials.gov Identifier: NCT01855048
• Other Study ID Numbers: SAL200-1A
• First Posted: May 16, 2013
• Last Update Posted: Nov 3, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Intron Biotechnology, Inc.: N-Rephasin® SAL200; endolysin; Placebo
• Additional relevant MeSH terms: Staphylococcal Infections

Study Results

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 Detail	57 subjects were screened and 36 subjects met the eligibility criteria.

Arm/Group Title	INT200-Placebo	N-Rephasin® SAL200, 0.1mg/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
Arm/Group Description	Placebo INT200-Placebo: Formulation buffer for continuous intravenous infusion over 60 minutes	N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes	N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes	N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes	N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes	N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes
Period Title: Overall Study
STARTED	9	3	6	6	6	6
COMPLETED	9	2	6	6	5	6
NOT COMPLETED	0	1	0	0	1	0

Baseline Characteristics

Arm/Group Title	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
Arm/Group Description	N-Rephasin® SAL200, 0.1 mg/kg N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes	N-Rephasin® SAL200, 0.3 mg/kg N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes	N-Rephasin® SAL200, 1 mg/kg N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes	N-Rephasin® SAL200, 3 mg/kg N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes	N-Rephasin® SAL200, 10 mg/kg N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes	Placebo INT200-Placebo: Formulation buffer for continuous intravenous infusion over 60 minutes	Total of all reporting groups
Overall Participants	3	6	6	6	6	9	36
Age, Customized (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	25.3	27.8	29.8	23.7	30.5	26.2	27.4
Sex/Gender, Customized (Count of Participants)
Male	3 100%	6 100%	6 100%	6 100%	6 100%	9 100%	36 100%
Race/Ethnicity, Customized (Count of Participants)
Asian	3 100%	6 100%	6 100%	6 100%	6 100%	9 100%	36 100%
Region of Enrollment (participants) [Number]
South Korea	3 100%	6 100%	6 100%	6 100%	6 100%	9 100%	36 100%
Body weight (kg) [Mean (Full Range) ]
Mean (Full Range) [kg]	67.1	65.5	74.0	69.1	68.7	68.1	68.9
Height (cm) [Mean (Full Range) ]
Mean (Full Range) [cm]	176.8	171.3	175.1	174.8	170.5	174.5	173.6

Outcome Measures

1. Primary Outcome

Title	Evaluation of the Safety of N-Rephasin® SAL200 in Healthy Human Volunteers
Time Frame	Up to 50 days after administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	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)
Arm/Group Description	INT200-Placebo, IV administration	Study drug 0.0056 mL/kg, IV administration	Study drug 0.017 mL/kg, IV administration	Study drug 0.056 mL/kg, IV administration	Study drug 0.167 mL/kg, IV administration	Study drug 0.556 mL/kg, IV administration
Measure Participants	9	3	6	6	6	6
Number of Subjects with at least one AE	1 33.3%	0 0%	2 33.3%	1 16.7%	2 33.3%	6 66.7%
Number of Subjects with at least one drug-related AE	1 33.3%	0 0%	2 33.3%	1 16.7%	0 0%	6 66.7%

2. Other Pre-specified Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Rephasin® SAL200 0.1mg/kg	N-Rephasin® SAL200 0.3mg/kg	N-Rephasin® SAL200 1mg/kg	N-Rephasin® SAL200 3mg/kg	N-Rephasin® SAL200 10mg/kg
Arm/Group Description	Study drug 0.0056 mL/kg, IV administration	Study drug 0.017 mL/kg, IV administration	Study drug 0.056 mL/kg, IV administration	Study drug 0.167 mL/kg, IV administration	Study drug 0.556 mL/kg, IV administration
Measure Participants	3	6	6	6	6
Mean (Standard Deviation) [h]	0.04 (0.02)	0.04 (0.01)	0.25 (0.05)	0.38 (0.06)	0.38 (0.05)

3. Other Pre-specified Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	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
Arm/Group Description	Study drug 0.0056 mL/kg, IV administration	Study drug 0.017 mL/kg, IV administration	Study drug 0.056 mL/kg, IV administration	Study drug 0.167 mL/kg, IV administration	Study drug 0.556 mL/kg, IV administration
Measure Participants	3	6	6	6	6
0h	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
1h	0 (0)	0 (0)	0.13 (0.05)	0.22 (0.10)	0.40 (0.13)
1.5h	0 (0)	0 (0)	0 (0)	0 (0)	0.15 (0.06)
2h	0 (0)	0 (0)	0 (0)	0 (0)	0.04 (0.05)

4. Other Pre-specified Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Rephasin® SAL200 0.1mg/kg	N-Rephasin® SAL200 0.3mg/kg	N-Rephasin® SAL200 1mg/kg	N-Rephasin® SAL200 3mg/kg	N-Rephasin® SAL200 10mg/kg
Arm/Group Description	Study drug 0.0056 mL/kg, IV administration	Study drug 0.017 mL/kg, IV administration	Study drug 0.056 mL/kg, IV administration	Study drug 0.167 mL/kg, IV administration	Study drug 0.556 mL/kg, IV administration
Measure Participants	3	6	6	6	6
Mean (Standard Deviation) [µg/ml]	0.04 (0.01)	0.09 (0.04)	0.82 (0.50)	7.10 (5.39)	55.99 (10.37)

5. Other Pre-specified Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Rephasin® SAL200 0.1mg/kg	N-Rephasin® SAL200 0.3mg/kg	N-Rephasin® SAL200 1mg/kg	N-Rephasin® SAL200 3mg/kg	N-Rephasin® SAL200 10mg/kg
Arm/Group Description	Study drug 0.0056 mL/kg, IV administration	Study drug 0.017 mL/kg, IV administration	Study drug 0.056 mL/kg, IV administration	Study drug 0.167 mL/kg, IV administration	Study drug 0.556 mL/kg, IV administration
Measure Participants	3	6	6	6	6
Mean (Standard Deviation) [µg/ml/mg]	0.01 (0.001)	0.005 (0.001)	0.01 (0.01)	0.03 (0.02)	0.08 (0.01)

6. Other Pre-specified Outcome

Title	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	N-Rephasin® SAL200 0.1mg/kg	N-Rephasin® SAL200 0.3mg/kg	N-Rephasin® SAL200 1mg/kg	N-Rephasin® SAL200 3mg/kg	N-Rephasin® SAL200 10mg/kg
Arm/Group Description	Study drug 0.0056 mL/kg, IV administration	Study drug 0.017 mL/kg, IV administration	Study drug 0.056 mL/kg, IV administration	Study drug 0.167 mL/kg, IV administration	Study drug 0.556 mL/kg, IV administration
Measure Participants	3	69	6	6	6
Mean (Standard Deviation) [µg*h/ml]	0.03 (0.005)	0.05 (0.02)	0.57 (0.31)	7.26 (3.42)	59.79 (9.03)

Adverse Events

Time Frame	Up to 50 Days ± 7 Days
Arm/Group Title	INT200-Placebo		N-Rephasin® SAL200, 0.1mg/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
Arm/Group Description	Placebo INT200-Placebo: Formulation buffer for continuous intravenous infusion over 60 minutes		N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes		N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes		N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes		N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes		N-Rephasin® SAL200: continuous intravenous infusion over 60 minutes
All Cause Mortality
	INT200-Placebo		N-Rephasin® SAL200, 0.1mg/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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Serious Adverse Events
	INT200-Placebo		N-Rephasin® SAL200, 0.1mg/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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/3 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	INT200-Placebo		N-Rephasin® SAL200, 0.1mg/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
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/9 (11.1%)		0/3 (0%)		2/6 (33.3%)		1/6 (16.7%)		2/6 (33.3%)		6/6 (100%)
Gastrointestinal disorders
Abdominal pain	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1
Diarrhoea	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Nausea	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2
Dyspepsia	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
General disorders
Fatigue	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	3/6 (50%)	3
Fever	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Rigors	0/9 (0%)	0	0/3 (0%)	0	2/6 (33.3%)	2	0/6 (0%)	0	0/6 (0%)	0	4/6 (66.7%)	4
Hepatobiliary disorders
Bilirubinaemia	0/9 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Myalgia	0/9 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	3
Nervous system disorders
Headache	1/9 (11.1%)	3	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	3/6 (50%)	3
Dizziness	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	2
Syncope	0/9 (0%)	0	0/3 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Coughing	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1
Pharyngitis	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1
Rhinitis	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	4/6 (66.7%)	4
Vascular disorders
Hypotension	0/9 (0%)	0	0/3 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.