A Safety and Efficacy Study of Doripenem in Participants With Nosocomial Pneumonia, Complicated Intra-Abdominal Infections and Urinary Tract Infections

• Sponsor: Janssen-Cilag Ltd.,Thailand (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00965848
• Collaborator: (none)
• Enrollment: 270
• Locations: 9
• Arms: 3
• Duration (Months): 13
• Patients Per Site: 30
• Patients Per Site Per Month: 2.3

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and efficacy of doripenem in participants with nosocomial pneumonia (inflammation of the lungs in which the lungs become heavy; pneumonia occurring at least 48 hours after hospital admission), complicated intra-abdominal (in belly) infections and complicated urinary tract infections (bladder infections).

Condition or Disease	Intervention/Treatment	Phase
Infection; Cross Infection; Bacterial Infections; Pneumonia, Ventilator-Associated; Intra-abdominal Infections; Urinary Tract Infections	Drug: Doripenem	Phase 4

Detailed Description

This is an open-label (all people involved know the identity of the intervention), multi-center (conducted in more than 1 center) study, to evaluate the safety and effectiveness of doripenem in treating Thai participants with nosocomial pneumonia, complicated intra-abdominal and urinary tract infections. The study consists of 4 visits: Visit 1 (Baseline), Visit 2 (End-of-Treatment [EOT], up to Day 14), Visit 3 (Phone visit, Test-of-Cure [TOC], up to Day 14 after EOT) and Visit 4 (Phone visit, Day 90). Participants will receive 500 milligram (mg) of doripenem as intravenous infusion (directly into the vein) every 8 hours for at least 3 days after clinical response and extended up to 14 days. Efficacy will primarily be evaluated by determination of clinical response. Participants' safety will be monitored throughout the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 270 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Post Marketing Surveillance Study on the Safety and Effectiveness of Doripenem in the Therapy of Thai Patients With Nosocomial Pneumonia, Complicated Intra-Abdominal Infections and Complicated Urinary Tract Infections
• Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nosocomial Pneumonia Doripenem will be administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with nosocomial pneumonia up to maximum of 14 days.	Drug: Doripenem; Doripenem 500 mg will be administered as 1 or 4 hours intravenous infusion, after every 8 hours up to maximum of 14 days.; Other Names: Doribax
Experimental: Complicated Intra-Abdominal Infections Doripenem will be administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated intra-abdominal infections up to maximum of 14 days.	Drug: Doripenem; Doripenem 500 mg will be administered as 1 or 4 hours intravenous infusion, after every 8 hours up to maximum of 14 days.; Other Names: Doribax
Experimental: Complicated Urinary Tract Infections Doripenem will be administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated urinary tract infections up to maximum of 10 days.	Drug: Doripenem; Doripenem 500 mg will be administered as 1 or 4 hours intravenous infusion, after every 8 hours up to maximum of 14 days.; Other Names: Doribax

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) and Number of Participants Discontinued Because of AEs [Up to 30 days after last dose of study drug]

   An adverse event is any untoward medical occurrence in a participant administered with a pharmaceutical product. An adverse event does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The number of participants discontinued because of AEs were also reported.

Secondary Outcome Measures

1. Percentage of Participants With Clinical Response at End-of-Treatment (EOT) [Up to Day 14 (EOT)]

   Clinical response was defined as cure, improvement, failure and indeterminate. Cure=All signs/symptoms resolved/improved/lack of progression of all abnormalities; Improvement=Signs/symptoms of disease improved/resolved/ no modification in antibiotic therapy required & no worsening/appearance of new signs & symptoms of disease; Failure=Persistence or worsening of signs/symptoms of disease or emergence of new signs/symptoms and require any other antimicrobial therapy; and Indeterminate=Insufficient data for treatment evaluation. 2 subjects were lost to follow-up.

2. Percentage of Participants With Clinical Response at Test-of-Cure (TOC) [Up to Day 14 after End-of-Treatment (EOT)]

   Clinical response was defined as cure, improvement, failure and indeterminate. Cure=All signs/symptoms resolved/improved/lack of progression of all abnormalities; Improvement=Signs/symptoms of disease improved/resolved/ no modification in antibiotic therapy required and no worsening/appearance of new signs & symptoms of disease; Failure=Persistence or worsening of signs/symptoms of disease or emergence of new signs/symptoms & require any other antimicrobial therapy; & Indeterminate=Insufficient data for treatment evaluation. The TOC visit (up to Day 14 after EOT) was conducted by phone. Participants who were assessed as cure or improvement at EOT will be evaluated for clinical response at TOC (up to Day 14 after EOT).

3. Number of Participants With 90-day Mortality [up to Day 90]

   Number of Participants with 90-day mortality was defined as the number of participants who died by Day 90.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Eligibility Criteria:

Inclusion Criteria:

• Male or female participants with 18 years old age and above

• Diagnosed nosocomial pneumonia, complicated intra-abdominal infections and complicated urinary tract infections

• Must have evidence of a systemic inflammatory response syndrome with at least one of the these: fever (body temperature greater than 38 degree celcius) or hypothermia (body temperature less than 36 degree celcius) or elevated total peripheral white blood cell count greater than or equal to 12,000 cells per cubic millimeter or leukopenia with less than 4,000 cells per cubic millimeter or decrease in blood pressure relative to Baseline of greater than 15 millimeter of mercury systolic or increased pulse greater than 100 beats per minute (bpm) and respiratory rates greater than 20 bpm

• Candidate for treatment with carbapenems, with at least one of these conditions: Empirical therapy; suspected infection caused by carbapenem susceptible P. aeruginosa or carbapenem-susceptible A. baumannii or MDR gram negative bacteria or nosocomial infection with failure of previous treatment or modified therapy; known pathogens with resistance to cephalosporins,aminoglycosides, fluoroquinolones or beta-lactam/ batalactamase intibitor and susceptible to carbapenem or known infection caused by gram negative bacteria

• Signed informed consent

Exclusion Criteria:

• Pregnant or lactating female participants

• History of severe allergies to antibiotics such as penicillins, cephalosporins and carbapenems

• Hypersensitivity to doripenem and/or excipients

• Previous use of carbapenems within 7 days of study entry

• Participants in terminal stage of malignancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Bangkok		Thailand
2		Chiang Mai		Thailand
3		Chiang Rai		Thailand
4		Chonburi		Thailand
5		Khon Kaen		Thailand
6		Khon Khen		Thailand
7		Nakhonratsima		Thailand
8		Nakornnayok		Thailand
9		Pathumthani		Thailand

Sponsors and Collaborators

• Janssen-Cilag Ltd.,Thailand

Investigators

• Study Director: Janssen-Cilag Ltd.,Thailand Clinical Trial, Janssen-Cilag Ltd.,Thailand

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen-Cilag Ltd.,Thailand
• ClinicalTrials.gov Identifier: NCT00965848
• Other Study ID Numbers: CR015766; DORIBAC4003
• First Posted: Aug 26, 2009
• Last Update Posted: Oct 30, 2013
• Last Verified: Sep 1, 2013

• Keywords provided by Janssen-Cilag Ltd.,Thailand: Pneumonia, Ventilator-Associated; Intra-abdominal Infections; Urinary tract Infections; Doripenem; Doribax
• Additional relevant MeSH terms: Infections; Communicable Diseases; Pneumonia; Urinary Tract Infections; Bacterial Infections; Intraabdominal Infections; Healthcare-Associated Pneumonia; Pneumonia, Ventilator-Associated; Cross Infection; Doripenem

Study Results

Participant Flow

Pre-assignment Detail	The total number of participants enrolled were 270, out of which 268 participants had adequate information for analysis.

Arm/Group Title	Nosocomial Pneumonia	Complicated Intra-Abdominal Infections	Complicated Urinary Tract Infections
Arm/Group Description	Doripenem was administered as 1 or 4 hours intravenous infusion (directly into the vein) at a dose of 500 milligram (mg) every 8 hours in participants with nosocomial pneumonia up to maximum of 14 days.	Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated intra-abdominal infections up to maximum of 14 days.	Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated urinary tract infections up to maximum of 10 days.
Period Title: Overall Study
STARTED	107	34	127
COMPLETED	78	32	117
NOT COMPLETED	29	2	10

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description
Overall Participants	264
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.6 (16.5)
Sex: Female, Male (Count of Participants)
Female	118 44.7%
Male	146 55.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Number of Participants Discontinued Because of AEs
Description	An adverse event is any untoward medical occurrence in a participant administered with a pharmaceutical product. An adverse event does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. The number of participants discontinued because of AEs were also reported.
Time Frame	Up to 30 days after last dose of study drug

Outcome Measure Data

Analysis Population Description

Intent-to-treat population (ITT) included all participants who received at least one dose of study medication.

Arm/Group Title	Nosocomial Pneumonia	Complicated Intra-Abdominal Infections	Complicated Urinary Tract Infections
Arm/Group Description	Doripenem was administered as 1 or 4 hours intravenous infusion (directly into the vein) at a dose of 500 milligram (mg) every 8 hours in participants with nosocomial pneumonia up to maximum of 14 days.	Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated intra-abdominal infections up to maximum of 14 days.	Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated urinary tract infections up to maximum of 10 days.
Measure Participants	107	34	127
Participants with AEs	66 25%	22 NaN	56 NaN
Participants discontinued because of AEs	0 0%	0 NaN	2 NaN

2. Secondary Outcome

Title	Percentage of Participants With Clinical Response at End-of-Treatment (EOT)
Description	Clinical response was defined as cure, improvement, failure and indeterminate. Cure=All signs/symptoms resolved/improved/lack of progression of all abnormalities; Improvement=Signs/symptoms of disease improved/resolved/ no modification in antibiotic therapy required & no worsening/appearance of new signs & symptoms of disease; Failure=Persistence or worsening of signs/symptoms of disease or emergence of new signs/symptoms and require any other antimicrobial therapy; and Indeterminate=Insufficient data for treatment evaluation. 2 subjects were lost to follow-up.
Time Frame	Up to Day 14 (EOT)

Outcome Measure Data

Analysis Population Description

Clinical Modified-Intent-to-Treat (cMITT) included all participants who received any dose of study medication. "N" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.

Arm/Group Title	Nosocomial Pneumonia	Complicated Intra-Abdominal Infections	Complicated Urinary Tract Infections
Arm/Group Description	Doripenem was administered as 1 or 4 hours intravenous infusion (directly into the vein) at a dose of 500 milligram (mg) every 8 hours in participants with nosocomial pneumonia up to maximum of 14 days.	Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated intra-abdominal infections up to maximum of 14 days.	Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated urinary tract infections up to maximum of 10 days.
Measure Participants	97	33	125
Cure	38.1 14.4%	57.6 NaN	71.2 NaN
Improvement	30.9 11.7%	33.3 NaN	20.8 NaN
Failure	11.3 4.3%	6.1 NaN	1.6 NaN
Indeterminate	18.6 7%	3.0 NaN	5.6 NaN
Other: Lost to Follow-Up	1.0 0.4%	0.0 NaN	0.8 NaN

3. Secondary Outcome

Title	Percentage of Participants With Clinical Response at Test-of-Cure (TOC)
Description	Clinical response was defined as cure, improvement, failure and indeterminate. Cure=All signs/symptoms resolved/improved/lack of progression of all abnormalities; Improvement=Signs/symptoms of disease improved/resolved/ no modification in antibiotic therapy required and no worsening/appearance of new signs & symptoms of disease; Failure=Persistence or worsening of signs/symptoms of disease or emergence of new signs/symptoms & require any other antimicrobial therapy; & Indeterminate=Insufficient data for treatment evaluation. The TOC visit (up to Day 14 after EOT) was conducted by phone. Participants who were assessed as cure or improvement at EOT will be evaluated for clinical response at TOC (up to Day 14 after EOT).
Time Frame	Up to Day 14 after End-of-Treatment (EOT)

Outcome Measure Data

Analysis Population Description

The cMITT included all participants who received any dose of study medication. "N" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.

Arm/Group Title	Nosocomial Pneumonia	Complicated Intra-Abdominal Infections	Complicated Urinary Tract Infections
Arm/Group Description	Doripenem was administered as 1 or 4 hours intravenous infusion (directly into the vein) at a dose of 500 milligram (mg) every 8 hours in participants with nosocomial pneumonia up to maximum of 14 days.	Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated intra-abdominal infections up to maximum of 14 days.	Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated urinary tract infections up to maximum of 10 days.
Measure Participants	62	24	93
Cure	56.96 21.6%	66.67 NaN	85.42 NaN
Improvement	0.00 0%	0.00 NaN	0.00 NaN
Failure	5.06 1.9%	7.41 NaN	6.25 NaN
Indeterminate	15.19 5.8%	14.81 NaN	5.21 NaN
Other: Lost to Follow-Up	1.27 0.5%	0.00 NaN	0.00 NaN
Not evaluable	21.52 8.2%	11.11 NaN	3.13 NaN

4. Secondary Outcome

Title	Number of Participants With 90-day Mortality
Description	Number of Participants with 90-day mortality was defined as the number of participants who died by Day 90.
Time Frame	up to Day 90

Outcome Measure Data

Analysis Population Description

The cMITT included all participants who received any dose of study medication and met the clinical definition in the protocol. "N" signifies those participants who were evaluated for this measure.

Arm/Group Title	Nosocomial Pneumonia	Complicated Intra-Abdominal Infections	Complicated Urinary Tract Infections
Arm/Group Description	Doripenem was administered as 1 or 4 hours intravenous infusion (directly into the vein) at a dose of 500 milligram (mg) every 8 hours in participants with nosocomial pneumonia up to maximum of 14 days.	Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated intra-abdominal infections up to maximum of 14 days.	Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated urinary tract infections up to maximum of 10 days.
Measure Participants	89	34	116
Number [Participants]	42 15.9%	16 NaN	22 NaN

Adverse Events

Time Frame	Baseline up to 30 days after last dose of study drug
Adverse Event Reporting Description	An adverse event is any untoward medical occurrence in a clinical study participant administered with study treatment. It can be any unfavorable and unintended sign/abnormal finding, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.
Arm/Group Title	Nosocomial Pneumonia		Complicated Intra-Abdominal Infections		Complicated Urinary Tract Infections
Arm/Group Description	Doripenem was administered as 1 or 4 hours intravenous infusion (directly into the vein) at a dose of 500 milligram (mg) every 8 hours in participants with nosocomial pneumonia up to maximum of 14 days.		Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated intra-abdominal infections up to maximum of 14 days.		Doripenem was administered as 1 or 4 hours intravenous infusion at a dose of 500 mg every 8 hours in participants with complicated urinary tract infections up to maximum of 10 days.
All Cause Mortality
	Nosocomial Pneumonia		Complicated Intra-Abdominal Infections		Complicated Urinary Tract Infections
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Nosocomial Pneumonia		Complicated Intra-Abdominal Infections		Complicated Urinary Tract Infections
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/107 (42.1%)		14/34 (41.2%)		31/127 (24.4%)
Blood and lymphatic system disorders
Neutropenia	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Cardiac disorders
Bradycardia	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Myocardial infarction	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Right ventricular failure	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Sudden cardiac death	3/107 (2.8%)		1/34 (2.9%)		1/127 (0.8%)
Ventricular tachycardia	3/107 (2.8%)		0/34 (0%)		0/127 (0%)
Acute myocardial infarction	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Arrhythmia	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Cardiac arrest	0/107 (0%)		1/34 (2.9%)		2/127 (1.6%)
Gastrointestinal disorders
Colorectal cancer	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Gastrointestinal haemorrhage	2/107 (1.9%)		1/34 (2.9%)		0/127 (0%)
Pancreatic carcinoma	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Gingival bleeding	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Peritonitis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
General disorders
Death	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Multi-organ failure	0/107 (0%)		4/34 (11.8%)		0/127 (0%)
Hepatobiliary disorders
Acute hepatic failure	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Bile duct cancer	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Cholangitis	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Cholangitis acute	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Hepatic neoplasm malignant	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Immune system disorders
Anaphylactic reaction	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Infections and infestations
Acquired immunodeficiency syndrome	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Bacterial sepsis	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Bronchopulmonary aspergillosis	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Catheter related infection	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Clostridium difficile colitis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Fungal sepsis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
HIV infection	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Pneumonia	10/107 (9.3%)		2/34 (5.9%)		4/127 (3.1%)
Pyelonephritis acute	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Sepsis	7/107 (6.5%)		5/34 (14.7%)		3/127 (2.4%)
Septic shock	10/107 (9.3%)		4/34 (11.8%)		9/127 (7.1%)
Urinary tract infection	1/107 (0.9%)		0/34 (0%)		3/127 (2.4%)
Urosepsis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Wound infection	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Wound sepsis	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Injury, poisoning and procedural complications
Drug prescribing error	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Overdose	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Musculoskeletal and connective tissue disorders
Myasthenias	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hypopharyngeal cancer	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Nervous system disorders
Convulsion	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Subarachnoid haemorrhage	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Renal and urinary disorders
Bladder cancer	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Haematuria	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Renal failure	1/107 (0.9%)		1/34 (2.9%)		0/127 (0%)
Renal failure acute	2/107 (1.9%)		1/34 (2.9%)		2/127 (1.6%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Dyspnoea	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Lung cancer metastatic	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Lung neoplasm malignant	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Pleural effusion	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Pneumonia	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Pneumonia aspiration	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Pulmonary oedema	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Respiratory failure	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Vascular disorders
Hypotension	2/107 (1.9%)		0/34 (0%)		2/127 (1.6%)
Other (Not Including Serious) Adverse Events
	Nosocomial Pneumonia		Complicated Intra-Abdominal Infections		Complicated Urinary Tract Infections
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	66/107 (61.7%)		22/34 (64.7%)		56/127 (44.1%)
Blood and lymphatic system disorders
Agranulocytosis	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Anaemia	1/107 (0.9%)		0/34 (0%)		3/127 (2.4%)
Thrombocytopenia	1/107 (0.9%)		1/34 (2.9%)		1/127 (0.8%)
Gastrointestinal disorders
Abdominal distension	1/107 (0.9%)		0/34 (0%)		1/127 (0.8%)
Abdominal pain	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Constipation	3/107 (2.8%)		2/34 (5.9%)		1/127 (0.8%)
Diarrhoea	7/107 (6.5%)		1/34 (2.9%)		2/127 (1.6%)
Gastrointestinal haemorrhage	1/107 (0.9%)		0/34 (0%)		2/127 (1.6%)
Ileus	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Nausea	0/107 (0%)		0/34 (0%)		2/127 (1.6%)
Oral candidiasis	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
General disorders
Fatigue	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Pain	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Pyrexia	1/107 (0.9%)		0/34 (0%)		3/127 (2.4%)
Hepatobiliary disorders
Cholangitis	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Hepatic encephalopathy	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Jaundice cholestatic	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Immune system disorders
Drug eruption	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Drug hypersensitivity	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Infections and infestations
Abdominal infection	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Bacteraemia	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Candida sepsis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Catheter related infection	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Clostridium difficile colitis	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Fungal cystitis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Herpes simplex	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Nasopharyngitis	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Oral herpes	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Peritonitis bacterial	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Pneumonia	1/107 (0.9%)		2/34 (5.9%)		3/127 (2.4%)
Sepsis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Septic shock	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Skin candida	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Skin infection	2/107 (1.9%)		0/34 (0%)		1/127 (0.8%)
Stenotrophomonas infection	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Strongyloidiasis	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Systemic candida	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Tinea cruris	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Urinary tract infection	2/107 (1.9%)		1/34 (2.9%)		4/127 (3.1%)
Urinary tract infection enterococcal	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Vulvovaginal candidiasis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Injury, poisoning and procedural complications
Application site itching	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Investigations
Alanine aminotransferase increased	2/107 (1.9%)		0/34 (0%)		0/127 (0%)
Aspartate aminotransferase increased	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Blood creatinine increased	2/107 (1.9%)		0/34 (0%)		0/127 (0%)
Blood urea increased	1/107 (0.9%)		1/34 (2.9%)		1/127 (0.8%)
Hepatic enzyme increased	3/107 (2.8%)		1/34 (2.9%)		1/127 (0.8%)
Transaminase increased	1/107 (0.9%)		0/34 (0%)		2/127 (1.6%)
Metabolism and nutrition disorders
Hypercalcaemia	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Hyperglycaemia	2/107 (1.9%)		0/34 (0%)		0/127 (0%)
Hyperkalaemia	3/107 (2.8%)		0/34 (0%)		1/127 (0.8%)
Hypokalaemia	4/107 (3.7%)		2/34 (5.9%)		5/127 (3.9%)
Hypomagnesaemia	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Hyponatraemia	0/107 (0%)		1/34 (2.9%)		1/127 (0.8%)
Hypophosphataemia	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Hypothyroidism	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Gout	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Gouty arthritis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Musculoskeletal chest pain	2/107 (1.9%)		0/34 (0%)		0/127 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Nervous system disorders
Convulsion	2/107 (1.9%)		0/34 (0%)		1/127 (0.8%)
Dizziness	0/107 (0%)		0/34 (0%)		2/127 (1.6%)
Insomnia	1/107 (0.9%)		0/34 (0%)		1/127 (0.8%)
Psychiatric disorders
Anxiety	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Delirium	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Renal and urinary disorders
Haematuria	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Pyuria	0/107 (0%)		0/34 (0%)		2/127 (1.6%)
Renal failure acute	4/107 (3.7%)		0/34 (0%)		2/127 (1.6%)
Urinary tract infection	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchitis	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Nasal congestion	0/107 (0%)		1/34 (2.9%)		0/127 (0%)
Pneumonia	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Pneumonia aspiration	0/107 (0%)		0/34 (0%)		2/127 (1.6%)
Pneumothorax	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Tracheobronchitis	1/107 (0.9%)		0/34 (0%)		1/127 (0.8%)
Skin and subcutaneous tissue disorders
Cellulitis	2/107 (1.9%)		0/34 (0%)		0/127 (0%)
Dermatitis	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Dermatitis bullous	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Eczema	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Rash	5/107 (4.7%)		1/34 (2.9%)		2/127 (1.6%)
Rash maculo-papular	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Surgical and medical procedures
Tracheostomy	1/107 (0.9%)		0/34 (0%)		0/127 (0%)
Vascular disorders
Haematoma	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Hypertension	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Hypotension	0/107 (0%)		0/34 (0%)		1/127 (0.8%)
Phlebitis	2/107 (1.9%)		2/34 (5.9%)		1/127 (0.8%)
Thrombophlebitis	1/107 (0.9%)		0/34 (0%)		0/127 (0%)

Limitations/Caveats

[Not Specified]

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

If the Institution & Principal Investigator wish to publish information from Clinical Trial, a copy of manuscript must be provided to Sponsor at least 60 days prior to submission for publication/presentation & will arrange expedited reviews for the same. No paper with confidential Information will be submitted without Sponsor's prior consent. If requested, Institution & Principal Investigator will hold such publication for up to additional 60 days to allow filing of patent application.