Phase IIa Clinical Study of N-Rephasin® SAL200

• Sponsor: Intron Biotechnology, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03089697
• Collaborator: (none)
• Enrollment: 25
• Locations: 2
• Arms: 2
• Actual Duration (Months): 32
• Patients Per Site: 12.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study is performed to evaluate safety and to explore the efficacy of a single intravenous dose of N-Rephasin® SAL200 (3 mg/kg) in addition to the conventional standard treatment, for persistent Staphylococcus aureus bacteremia in patients, for more than 48 hours even after antibiotic treatment to which Staphylococcus aureus is susceptible.

Condition or Disease	Intervention/Treatment	Phase
Staphylococcus Aureus Bacteremia; Anti-Bacterial Agents	Biological: N-Rephasin® SAL200; Other: Placebo	Phase 2

Detailed Description

Subjects:

Patients with persistent Staphylococcus aureus bacteremia for more than 48 hours from the beginning of antibiotics treatment to which Staphylococcus aureus is susceptible.

Study Method:

1. Selection of patients with persistent S.aureus bacteremia for more than 48 hours even after application of the standard treatment for S. aureus bacteremia

2. Randomization according to the trial institutions

3. The control group receives a single intravenous dose of the placebo in addition to the standard treatment for persistent Staphylococcus aureus bacteremia

4. The study group receives a single intravenous dose of the N-Rephasin® SAL200 (3 mg/kg) in addition to the standard treatment for persistent Staphylococcus aureus bacteremia

5. A blood culture is performed 18 hours (±6 hours) after the administration of N-Rephasin® SAL200

6. Blood cultures continue to be performed every 24 hours (±6 hours) or 48 hours (±6 hours) after the previous blood culture, until two consecutive results of 'no growth (negative conversion)' are obtained

7. Adverse events are monitored at the time of the first blood culture following the administration of N-Rephasin® SAL200 or placebo, and at the subsequent intervals of 24 hours or 48 hours

Statistical Analysis:

1. Primary endpoints

• Safety analysis is conducted in the Safety group. A distribution table of patients who experience at least one adverse event (incidence), and distribution tables of the relationship of the reported adverse events with the investigational product (distribution tables for severity and the relationship with the drug) are presented with respect to the groups (study group, control group), to determine safety of the investigational product.

• The results of the laboratory tests, anaphylaxis test, inflammatory cytokine test and vital signs at baseline and the last visit are summarized as mean values and standard deviations, to determine the change before and after the treatment within each group.

• Categorical data are divided into normal and abnormal, and summarized as the frequency and percentage to determine the difference before and after treatment within each group.

1. Secondary endpoints

• Proportion of patients who are negative for bacterial growth in the first blood culture after administration of the investigational drug. The descriptive statistics for the proportion of patients who are negative for bacterial growth in the first blood culture (the rate of no growth) after the first treatment are presented by treatment group. Whether the rate of no growth is superior in the study group compared to the control group, is evaluated by a descriptive statistical method.

• Proportion of patients who die due to S. aureus bacteremia by Day14 after the incidence of bacteremia. The descriptive statistics for the proportion of patients who die due to S. aureus bacteremia by Day14 are presented by treatment group and evaluated.

• Proportion of treatment failure for S. aureus bacteremia by Day 14 (if two consecutive results of 'no growth' are not achieved in the blood cultures which are performed until Day 14. The descriptive statistics for the proportion of treatment failure for S. aureus bacteremia by Day 14 are presented and evaluated.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 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, Multicenter Phase IIa Clinical Study to Evaluate Safety and to Explore Efficacy of N-Rephasin® SAL200, in Patients With Persistent Staphylococcus Aureus Bacteremia
• Actual Study Start Date: Mar 7, 2017
• Actual Primary Completion Date: Nov 7, 2019
• Actual Study Completion Date: Nov 7, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: N-Rephasin® SAL200 To assign the study group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with N-Rephasin® SAL200 (3mg/kg); N-Rephasin® SAL 200 is given by intravenous only once at Day 1.	Biological: N-Rephasin® SAL200; A single dose of SAL200 (SAL-1, 3mg/kg) intravenous administration of the study drug, in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA
Placebo Comparator: Placebo To assign the control group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with Formulation buffer (placebo); Placebo (INT200) is given by intravenous only once at Day 1 (same way with Experimental group)	Other: Placebo; A single dose of the formulation buffer (placebo), excluding the main ingredient of the study drug in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA

Outcome Measures

Primary Outcome Measures

1. Safety Endpoints - Summary of Treatment-emergent Adverse Events (Safety Set) [up to 4 Week ± 5 Days]

   The safety analysis was conducted based on the data of all AEs, physical examinations, clinical laboratory tests, and vital signs (blood pressure, pulse rate, body temperature, and respiratory rate) collected from the subjects. All subjects who enrolled in this study (13 subjects in the placebo group and 12 subjects in the N RephasinⓇ SAL200 group) were defined as the Safety Set and included in the analysis.

Secondary Outcome Measures

1. Efficacy Endpoints 1 [by day 14]

   Number of Participants With Negative Result in the First Blood Culture

2. Efficacy Endpoint 2 [by day 14]

   The Proportion (Percentage) of Subjects who Died of Staphylococcus aureus Bacteremia Within 14 Days of Bacteremia Diagnosis

3. Efficacy Endpoint 3 [by day 14]

   Proportion (Percentage) of Treatment Failure Against Staphylococcus aureus Bacteremia by Day 14

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with MSSA/MRSA bacteremia who are confirmed to have more than a pair of Gram positive bacteria in a blood culture conducted at 48~96 hours after the start of antibiotic treatment to which S. aureus is susceptible.

2. Males or females aged 19 years or older

3. Those who understand the explanatory notes for subjects, and sign the informed consent.

Exclusion Criteria:

1. Those who do not receive appropriate antibiotics within 48 hours after the occurrence of bacteremia (the time point of reporting it to the department of laboratory medicine)

2. The Gram positive strain, identified in a blood culture conducted at 48~96 hours after the start of antibiotic treatment to which S. aureus is susceptible, is not the same strain of S. aureus which was cultured when the definite diagnosis of S. aureus bacteremia was made

3. Those who pass 48 hours after confirmation of persistent S. aureus bacteremia through a blood culture conducted at 48~96 hours after the start of antibiotic treatment to which S. aureus is susceptible

4. Those who have symptoms of septic shock at the time of acquisition of the consent form

• Systolic blood pressure lower than 90 mmHg, or blood pressure lower than usual by more than 40 mmHg, in spite of the application of appropriate fluid therapy

• Requirement of hypertensor to maintain the systolic blood pressure at 90 mmHg or higher

1. Those who were infected with mixed bacterial species

2. Those who are hypersensitive to N-Rephasin® SAL200, who have a clinically significant hypersensitivity to it, or a past history there of

3. Pregnant or lactating women and women of child-bearing potential (who do not agree to take appropriate contraceptive measures during the trial period)

4. Those who participated in other clinical trial within 30 days prior to enrollment

5. Patients with any conditions that may interfere with study participation or accurate evaluation on investigator's judgment

6. Those who may die within 72 hours due to other serious complications (e.g., cerebral infarction, etc.), as per the investigator's judgment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do	Korea, Republic of	13620
2	Seoul National University Hospital	Seoul		Korea, Republic of	03080

Sponsors and Collaborators

• Intron Biotechnology, Inc.

Investigators

• Principal Investigator: Hong-Bin Kim, M.D, PhD, Seoul National University Bundang Hospital
• Principal Investigator: Wan Beom Park, M.D, PhD, Seoul National University Hospital

Study Documents (Full-Text)

• Study Protocol - May 9, 2019
• Statistical Analysis Plan - Dec 6, 2019

More Information

Additional Information:

• Etiene J, Fleurette J, Ninet JF, Favet P, Gruer LD. Staphylococcus endocarditis after dental extraction. Lancet. 1986;2:511-512
• Frency J, Brun Y, Bes M, Meugnier H, Grimont F, Grimon PAD, Newi C, Fleurette J. Staphylococcus lugdunensis sp. and Staphylococcus schleiferi sp. novel two species from human clinical specimens. Int Syst Bacteriol. 1998;38:168-172
• Seung-Ho Han et al., Monitoring of Methicillin-Resistant Staphylococcus aureus in Nasal Swabs Obtained fron Dental Clinic Healthcare Providers and Medical Environments Nurses. Int J Oral Biology. 2010;35:7-12
• Hyuk Min Lee, Dong Eun Yong, Kyungwon Lee., Antimicrobial Resistance of Clinically Important Bacteria Isolated from 12 Hospitals in Korea in 2004 . Korean Journal of Clinical Microbiology 2005;8(1):66-73
• Siegel JD, Rhinehart E, Jackson M, Chiarello L. Management of multidrug-resistant organisms in health care settings, 2006. Am J Infect Control 2007;35(10 SUPPL. 2):S165-93.
• Woo J-H, Song J-H, Cheong H-S, Lee E-K, Chae S-M, Kim N-J. Analysis of Economic Outcomes of Methicillin-Resistant Staphylococcus Aureus(MRSA) Bacteremia Using Retrospective Case-Control Study. Korean J Clin Pharm 2007;17(2):59-64.
• Lee, H, Yong, D, Lee, K, Hong, S, Kim, E, Jung, S, Park, Y, Choi, T, Eo, Y, Shin, J et al. Antimicrobial Resistance of Clinically Important Bacteria Isolated from 12 Hospitals in Korea in 2004. Korean J Clinical Microbiology 2005;8(1):66-73

Publications

None provided.

• Responsible Party: Intron Biotechnology, Inc.
• ClinicalTrials.gov Identifier: NCT03089697
• Other Study ID Numbers: ITB-101
• First Posted: Mar 24, 2017
• Last Update Posted: Oct 6, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Intron Biotechnology, Inc.: N-Rephasin SAL200; Methicillin-Sensitive Staphylococcus aureus; Methicillin Resistant Staphylococcus Aureus
• Additional relevant MeSH terms: Staphylococcal Infections; Bacteremia

Study Results

Participant Flow

Arm/Group Title	Placebo	N-Rephasin® SAL200
Arm/Group Description	To assign the control group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with Formulation buffer (placebo); Placebo (INT200) is given by intravenous only once at Day 1 (same way with Experimental group) Placebo: A single dose of the formulation buffer (placebo), excluding the main ingredient of the study drug in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA	To assign the study group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with N-Rephasin® SAL200 (3mg/kg); N-Rephasin® SAL 200 is given by intravenous only once at Day 1. N-Rephasin® SAL200: A single dose of SAL200 (SAL-1, 3mg/kg) intravenous administration of the study drug, in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA
Period Title: Overall Study
STARTED	13	12
COMPLETED	11	10
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Placebo	N-Rephasin® SAL200	Total
Arm/Group Description	To assign the control group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with Formulation buffer (placebo); Placebo (INT200) is given by intravenous only once at Day 1 (same way with Experimental group) Placebo: A single dose of the formulation buffer (placebo), excluding the main ingredient of the study drug in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA	To assign the study group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with N-Rephasin® SAL200 (3mg/kg); N-Rephasin® SAL 200 is given by intravenous only once at Day 1. N-Rephasin® SAL200: A single dose of SAL200 (SAL-1, 3mg/kg) intravenous administration of the study drug, in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA	Total of all reporting groups
Overall Participants	13	12	25
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	64.23	65.33	64.8
Sex: Female, Male (Count of Participants)
Female	5 38.5%	5 41.7%	10 40%
Male	8 61.5%	7 58.3%	15 60%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
South Korea	13 100%	12 100%	25 100%
Height (cm) (cm) [Mean (Full Range) ]
Mean (Full Range) [cm]	165.19	161.96	163.6
Weight (kg) (kg) [Mean (Full Range) ]
Mean (Full Range) [kg]	60.35	59.03	59.7

Outcome Measures

1. Primary Outcome

Title	Safety Endpoints - Summary of Treatment-emergent Adverse Events (Safety Set)
Description	The safety analysis was conducted based on the data of all AEs, physical examinations, clinical laboratory tests, and vital signs (blood pressure, pulse rate, body temperature, and respiratory rate) collected from the subjects. All subjects who enrolled in this study (13 subjects in the placebo group and 12 subjects in the N RephasinⓇ SAL200 group) were defined as the Safety Set and included in the analysis.
Time Frame	up to 4 Week ± 5 Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	N-Rephasin® SAL200
Arm/Group Description	To assign the control group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with Formulation buffer (placebo); Placebo (INT200) is given by intravenous only once at Day 1 (same way with Experimental group) Placebo: A single dose of the formulation buffer (placebo), excluding the main ingredient of the study drug in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA	To assign the study group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with N-Rephasin® SAL200 (3mg/kg); N-Rephasin® SAL 200 is given by intravenous only once at Day 1. N-Rephasin® SAL200: A single dose of SAL200 (SAL-1, 3mg/kg) intravenous administration of the study drug, in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA
Measure Participants	13	12
TEAE (Treatment-emergent AEs)	12 92.3%	10 83.3%
SAE	2 15.4%	2 16.7%
AEs leading to premature termination	1 7.7%	2 16.7%

2. Secondary Outcome

Title	Efficacy Endpoints 1
Description	Number of Participants With Negative Result in the First Blood Culture
Time Frame	by day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	N-Rephasin® SAL200
Arm/Group Description	To assign the control group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with Formulation buffer (placebo); Placebo (INT200) is given by intravenous only once at Day 1 (same way with Experimental group) Placebo: A single dose of the formulation buffer (placebo), excluding the main ingredient of the study drug in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA	To assign the study group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with N-Rephasin® SAL200 (3mg/kg); N-Rephasin® SAL 200 is given by intravenous only once at Day 1. N-Rephasin® SAL200: A single dose of SAL200 (SAL-1, 3mg/kg) intravenous administration of the study drug, in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA
Measure Participants	13	12
Count of Participants [Participants]	5 38.5%	6 50%

3. Secondary Outcome

Title	Efficacy Endpoint 2
Description	The Proportion (Percentage) of Subjects who Died of Staphylococcus aureus Bacteremia Within 14 Days of Bacteremia Diagnosis
Time Frame	by day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	N-Rephasin® SAL200
Arm/Group Description	To assign the control group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with Formulation buffer (placebo); Placebo (INT200) is given by intravenous only once at Day 1 (same way with Experimental group) Placebo: A single dose of the formulation buffer (placebo), excluding the main ingredient of the study drug in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA	To assign the study group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with N-Rephasin® SAL200 (3mg/kg); N-Rephasin® SAL 200 is given by intravenous only once at Day 1. N-Rephasin® SAL200: A single dose of SAL200 (SAL-1, 3mg/kg) intravenous administration of the study drug, in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA
Measure Participants	13	12
Count of Participants [Participants]	1 7.7%	1 8.3%

4. Secondary Outcome

Title	Efficacy Endpoint 3
Description	Proportion (Percentage) of Treatment Failure Against Staphylococcus aureus Bacteremia by Day 14
Time Frame	by day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	N-Rephasin® SAL200
Arm/Group Description	To assign the control group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with Formulation buffer (placebo); Placebo (INT200) is given by intravenous only once at Day 1 (same way with Experimental group) Placebo: A single dose of the formulation buffer (placebo), excluding the main ingredient of the study drug in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA	To assign the study group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with N-Rephasin® SAL200 (3mg/kg); N-Rephasin® SAL 200 is given by intravenous only once at Day 1. N-Rephasin® SAL200: A single dose of SAL200 (SAL-1, 3mg/kg) intravenous administration of the study drug, in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA
Measure Participants	13	12
Count of Participants [Participants]	3 23.1%	2 16.7%

Adverse Events

Time Frame	Up to 4 weeks +5 Days
Arm/Group Title	Placebo		N-Rephasin® SAL200
Arm/Group Description	To assign the control group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with Formulation buffer (placebo); Placebo (INT200) is given by intravenous only once at Day 1 (same way with Experimental group) Placebo: A single dose of the formulation buffer (placebo), excluding the main ingredient of the study drug in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA		To assign the study group, administer the conventional standard treatment (CST) (antibiotics) for MRSA/MSSA with N-Rephasin® SAL200 (3mg/kg); N-Rephasin® SAL 200 is given by intravenous only once at Day 1. N-Rephasin® SAL200: A single dose of SAL200 (SAL-1, 3mg/kg) intravenous administration of the study drug, in addition to the conventional standard treatment (antibiotics) for MRSA/MSSA
All Cause Mortality
	Placebo		N-Rephasin® SAL200
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/13 (15.4%)		2/12 (16.7%)
Serious Adverse Events
	Placebo		N-Rephasin® SAL200
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/13 (15.4%)		2/12 (16.7%)
Cardiac disorders
Acute infarction	1/13 (7.7%)	1	0/12 (0%)	0
Infections and infestations
Pneumonia	0/13 (0%)	0	1/12 (8.3%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/13 (0%)	0	1/12 (8.3%)	1
Respiratory failure, type 2	1/13 (7.7%)	1	0/12 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		N-Rephasin® SAL200
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)		10/12 (83.3%)
Blood and lymphatic system disorders
Anaemia	3/13 (23.1%)	3	3/12 (25%)	4
Thrombocytopenia	2/13 (15.4%)	2	0/12 (0%)	0
Iron deficiency anaemia	0/13 (0%)	0	1/12 (8.3%)	1
Cardiac disorders
Atrial fibrillation	2/13 (15.4%)	2	0/12 (0%)	0
Acute myocardial infarction	1/13 (7.7%)	1	0/12 (0%)	0
Tachycardia	1/13 (7.7%)	1	0/12 (0%)	0
Gastrointestinal disorders
Constipation	6/13 (46.2%)	6	4/12 (33.3%)	5
Diarrhoea	3/13 (23.1%)	3	2/12 (16.7%)	2
Nausea	2/13 (15.4%)	4	2/12 (16.7%)	2
Abdominal pain	1/13 (7.7%)	1	3/12 (25%)	3
Gastrointestinal haemorrhage	0/13 (0%)	0	2/12 (16.7%)	2
Anal incontinence	0/13 (0%)	0	1/12 (8.3%)	1
Ascites	0/13 (0%)	0	1/12 (8.3%)	1
Ileus paralytic	1/13 (7.7%)	1	0/12 (0%)	0
Lip ulceration	0/13 (0%)	0	1/12 (8.3%)	1
Mouth ulceration	0/13 (0%)	0	1/12 (8.3%)	1
Vomiting	0/13 (0%)	0	1/12 (8.3%)	1
Dyspepsia	1/13 (7.7%)	1	2/12 (16.7%)	2
General disorders
Pyrexia	3/13 (23.1%)	4	1/12 (8.3%)	1
Chills	0/13 (0%)	0	2/12 (16.7%)	3
Asthenia	0/13 (0%)	0	1/12 (8.3%)	1
Chest discomfort	1/13 (7.7%)	1	0/12 (0%)	0
Disease progression	1/13 (7.7%)	1	0/12 (0%)	0
Facial pain	1/13 (7.7%)	1	0/12 (0%)	0
Oedema peripheral	0/13 (0%)	0	1/12 (8.3%)	1
Pain	0/13 (0%)	0	1/12 (8.3%)	1
Infections and infestations
Cellulitis	1/13 (7.7%)	1	1/12 (8.3%)	1
Abscess	0/13 (0%)	0	1/12 (8.3%)	1
Clostridium difficile infection	1/13 (7.7%)	1	0/12 (0%)	0
Extradural abscess	1/13 (7.7%)	1	0/12 (0%)	0
Infection	1/13 (7.7%)	1	0/12 (0%)	0
Infective aneurysm	0/13 (0%)	0	1/12 (8.3%)	1
Infective spondylitis	1/13 (7.7%)	1	0/12 (0%)	0
Pneumonia	0/13 (0%)	0	1/12 (8.3%)	1
Psoas abscess	0/13 (0%)	0	1/12 (8.3%)	1
Investigations
Blood creatinine increased	0/13 (0%)	0	2/12 (16.7%)	2
Haemoglobin decreased	0/13 (0%)	0	2/12 (16.7%)	2
Blood urea increased	0/13 (0%)	0	1/12 (8.3%)	1
Urine output decreased	0/13 (0%)	0	1/12 (8.3%)	1
Metabolism and nutrition disorders
Decreased appetite	1/13 (7.7%)	1	1/12 (8.3%)	1
Hypoalbuminaemia	1/13 (7.7%)	1	1/12 (8.3%)	1
Hypokalaemia	0/13 (0%)	0	2/12 (16.7%)	2
Hypophosphataemia	2/13 (15.4%)	2	0/12 (0%)	0
Fluid imbalance	0/13 (0%)	0	1/12 (8.3%)	1
Hyperkalaemia	0/13 (0%)	0	1/12 (8.3%)	1
Hypermagnesaemia	0/13 (0%)	0	1/12 (8.3%)	1
Hypocalcaemia	1/13 (7.7%)	1	0/12 (0%)	0
Hyponatraemia	0/13 (0%)	0	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
Back pain	2/13 (15.4%)	2	1/12 (8.3%)	1
Pain in extremity	1/13 (7.7%)	1	2/12 (16.7%)	2
Joint swelling	0/13 (0%)	0	2/12 (16.7%)	2
Arthralgia	1/13 (7.7%)	1	0/12 (0%)	0
Musculoskeletal pain	0/13 (0%)	0	1/12 (8.3%)	1
Myositis	1/13 (7.7%)	1	0/12 (0%)	0
Nervous system disorders
Headache	1/13 (7.7%)	1	1/12 (8.3%)	1
Asterixis	0/13 (0%)	0	1/12 (8.3%)	1
Neuralgia	1/13 (7.7%)	1	0/12 (0%)	0
Neuropathy peripheral	1/13 (7.7%)	1	0/12 (0%)	0
Seizure	0/13 (0%)	0	1/12 (8.3%)	1
Tremor	0/13 (0%)	0	1/12 (8.3%)	1
Psychiatric disorders
Delirium	1/13 (7.7%)	1	2/12 (16.7%)	2
Insomnia	1/13 (7.7%)	1	0/12 (0%)	0
Mood altered	0/13 (0%)	0	1/12 (8.3%)	1
Renal and urinary disorders
Dysuria	1/13 (7.7%)	1	2/12 (16.7%)	2
Azotaemia	0/13 (0%)	0	1/12 (8.3%)	1
Oliguria	0/13 (0%)	0	1/12 (8.3%)	1
Urinary retention	0/13 (0%)	0	1/12 (8.3%)	1
Reproductive system and breast disorders
Pelvic fluid collection	0/13 (0%)	0	1/12 (8.3%)	1
Penis disorder	1/13 (7.7%)	1	0/12 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/13 (7.7%)	1	2/12 (16.7%)	2
Productive cough	0/13 (0%)	0	3/12 (25%)	3
Respiratory failure	1/13 (7.7%)	1	1/12 (8.3%)	1
Cough	0/13 (0%)	0	1/12 (8.3%)	1
Pleural effusion	0/13 (0%)	0	1/12 (8.3%)	1
Sputum retention	1/13 (7.7%)	1	0/12 (0%)	0
Wheezing	0/13 (0%)	0	1/12 (8.3%)	1
Pneumonia aspiration	0/13 (0%)	0	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/13 (7.7%)	1	2/12 (16.7%)	2
Pruritus	1/13 (7.7%)	1	1/12 (8.3%)	1
Blister	1/13 (7.7%)	1	0/12 (0%)	0
Petechiae	1/13 (7.7%)	1	0/12 (0%)	0
Surgical and medical procedures
Leg amputation	0/13 (0%)	0	1/12 (8.3%)	1
Vascular disorders
Hypotension	3/13 (23.1%)	4	1/12 (8.3%)	1
Hypertension	0/13 (0%)	0	1/12 (8.3%)	1

Limitations/Caveats

Enrollment into this study was terminated by the Sponsor prior to completion for strategic reasons (to initiate clinical development abroad).

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.