A Study To Evaluate The Safety Of Voriconazole As Treatment Of Invasive Aspergillosis (Fungal Infection) And Other Rare Molds In Children

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00836875
• Collaborator: (none)
• Enrollment: 31
• Locations: 25
• Arm: 1
• Actual Duration (Months): 48
• Patients Per Site: 1.2
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety profile of voriconazole (an antifungal drug) when used in children who have invasive aspergillosis (IA) and other rare systemic fungal infections.

Condition or Disease	Intervention/Treatment	Phase
Invasive Aspergillosis	Drug: Voriconazole	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Non-Randomized
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Open-label, Non-randomized, Multi-center Study To Investigate The Safety And Tolerability Of Voriconazole As Primary Therapy For Treatment Of Invasive Aspergillosis And Molds Such As Scedosporium Or Fusarium Species In Pediatric Patients.
• Actual Study Start Date: May 1, 2009
• Actual Primary Completion Date: May 1, 2013
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 1 Children from 2 to 17 years who have possible, probable or proven invasive aspergillosis, or other rare mold infection (eg, Scedosporium and Fusarium).

Drug: Voriconazole; All subjects will receive voriconazole for a minimum of 6 weeks and a maximum of 12 weeks. All subjects must receive intravenous (IV) voriconazole for the first week of therapy. Group 1: Subjects 2 to 11 years old and subjects 12 to 14 years old with low body weight (<50 kg) will receive 9 mg/kg IV every 12 hours (q12h) on day 1, then 8 mg/kg IV q12h starting day 2. If there is a significant clinical improvement after the first week of IV therapy, subjects may be switched to the step-down oral regimen (9 mg/kg PO q12h with a maximum dose of 350 mg PO q12h) at the discretion of the investigator. Group 2: Subjects 12 to 17 years old (excluding 12-14-year-olds weighing <50 kg) will receive 6 mg/kg IV q12h on day 1, then 4 mg/kg IV q12h starting day 2. Similar to Group 1, subjects may be switched to the step-down oral regimen (200 mg PO q12h) at the discretion of the investigator. Oral voriconazole can be administered as tablet or oral suspension.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Adverse Events (AEs) [Baseline, daily while hospitalized, Days 7, 14, 28, 42, 84, and 114, at end of treatment, and up to 1 month post treatment]

Secondary Outcome Measures

1. Percentage of Participants With a Global Response of Success [Weeks 6 and End of Treatment (EOT; up to Week 12)]

   Percentage of participants with global response of success at Weeks 6 and at EOT (up to Week 12). Global response of success was defined as a participant who achieved a complete or partial global response per the investigator. Complete response was defined as resolution of all clinical signs and symptoms PLUS resolution of 90 percent (%) or more of the lesions visible on radiological studies and attributed to invasive aspergillosis (IA) at Baseline. Partial response was defined as clinical improvement PLUS 50% to <90% resolution of the radiological lesions attributed to IA at Baseline.

2. All-Cause Mortality - Number of Participant Deaths [Week 6 and EOT (up to Week 12)]

   Number of participant deaths reported at Week 6 and at EOT (up to Week 12).

3. Attributable Mortality - Number of Participant Deaths [Weeks 6 and EOT (up to Week 12)]

   Number of participant deaths attributable to study drug reported at Week 6 and at EOT (up to Week 12).

4. Time to Death [Baseline up to 1 month post treatment]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Immunocompromised with clinically compatible illness.

• Diagnosis of proven or probable or possible Invasive Aspergillosis (based on a modified version of the revised EORTC/MSG consensus definitions).

• Diagnosis of infection due to Scedosporium or Fusarium species.

• Male and female from 2 to 17 years of age.

• Females with childbearing potential must have negative pregnancy test and be using appropriate contraception.

Exclusion Criteria:

• Allergy or hypersensitivity to the azole drugs.

• Female subjects who are pregnant or lactating.

• Patients who received more than four days of antifungal drugs to treat the current episode of invasive aspergillosis or rare mold infection.

• Received within 24 hours prior to enrollment drugs that may cause QT interval prolongation.

• Significant liver, kidney or heart dysfunction.

• Not expected to survive for at least 5 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital Los Angeles	Los Angeles	California	United States	90027
2	Children's Hospital & Research Center Oakland (CHRCO)	Oakland	California	United States	94609
3	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15224
4	The University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
5	Children's Pavilion, Virginia Commonwealth University Health System	Richmond	Virginia	United States	23219
6	Virginia Commonwealth University Health System, Hospital Pharmacy	Richmond	Virginia	United States	23298-0042
7	Pediatric Hematology and Oncology, Virginia Commonwealth University Health System	Richmond	Virginia	United States	23298
8	Virginia Commonwealth University/MCV Clinical Pathology	Richmond	Virginia	United States	23298
9	Virginia Commonwealth University	Richmond	Virginia	United States	23298
10	Alberta Children's Hospital, Pediatric Oncology Office	Calgary	Alberta	Canada	T3B 6A8
11	Alberta Children's Hospital	Calgary	Alberta	Canada	T3B 6A8
12	Fakultni nemocnice Brno	Brno		Czechia	625 00
13	Fakultni nemocnice Brno	Brno		Czechia	62500
14	UMC St. Radboud	Nijmegen		Netherlands	6500 HB
15	Klinika Transplantacji Szpiku, Onkologii i Hematologii Dzieciecej	Wroclaw		Poland	50-345
16	National University Hospital	Singapore		Singapore	119074
17	KK Women's and Children's Hospital	Singapore		Singapore	229899
18	Hospital General Universitari Vall D'Hebron	Barcelona		Spain	08035
19	Hospital Universitari Vall d'Hebron. Servicio de Farmacia	Barcelona		Spain	08035
20	Hospital Universitario Vall d'Hebron	Barcelona		Spain	08035
21	HOSPITAL UNIVERSITARIO 12 DE OCTUBRE Servicio de Farmacia	Madrid		Spain	28041
22	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
23	Department of Pediatrics, Faculty of Medicine, Siriraj Hospital, Mahidol University	Bangkok noi	Bangkok	Thailand	10700
24	Department of Pediatrics, Faculty of Medicine, Chulalongkorn University	Patumwan	Bangkok	Thailand	10330
25	Department of Pediatrics, Phramongkutklao hospital	Rajathevee	Bangkok	Thailand	10400

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00836875
• Other Study ID Numbers: A1501080; 2008-005275-10
• First Posted: Feb 4, 2009
• Last Update Posted: Jun 16, 2017
• Last Verified: May 1, 2017

• Keywords provided by Pfizer: Pediatrics voriconazole invasive fungal infection invasive aspergillosis immunocompromized
• Additional relevant MeSH terms: Aspergillosis; Voriconazole

Study Results

Participant Flow

Arm/Group Title	Voriconazole: 2 to <12 Years	Voriconazole: 12 to <18 Years
Arm/Group Description	Participants aged 2 to less than (<)12 years (and young adolescents aged 12 to 14 years weighing <50 kilograms [kg]) received a loading dose of voriconazole of 9 milligrams per kg (mg/kg), intravenously (IV), every 12 hours (q12h) for the first 24 hours, followed by maintenance dosing of 8 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral (PO) therapy and received 9 mg/kg PO voriconazole q12h for a maximum dose of 350 mg.	Participants aged 12 to <18 years (excluding those aged 12-14 years weighing <50 kg) received a loading dose of 6 mg/kg IV q12h for the first 24 hours followed by maintenance dosing of 4 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral therapy and received 200-300 mg PO q12h.
Period Title: Overall Study
STARTED	11	20
COMPLETED	8	17
NOT COMPLETED	3	3

Baseline Characteristics

Arm/Group Title	Voriconazole: 2 to <12 Years	Voriconazole: 12 to <18 Years	Total
Arm/Group Description	Participants aged 2 to less than (<)12 years (and young adolescents aged 12 to 14 years weighing <50 kilograms [kg]) received a loading dose of voriconazole of 9 milligrams per kg (mg/kg), intravenously (IV), every 12 hours (q12h) for the first 24 hours, followed by maintenance dosing of 8 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral (PO) therapy and received 9 mg/kg PO voriconazole q12h for a maximum dose of 350 mg.	Participants aged 12 to <18 years (excluding those aged 12-14 years weighing <50 kg) received a loading dose of 6 mg/kg IV q12h for the first 24 hours followed by maintenance dosing of 4 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral therapy and received 200-300 mg PO q12h.	Total of all reporting groups
Overall Participants	11	20	31
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.9 (2.3)	14.1 (1.7)	11.9 (3.5)
Sex: Female, Male (Count of Participants)
Female	4 36.4%	11 55%	15 48.4%
Male	7 63.6%	9 45%	16 51.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs)
Time Frame	Baseline, daily while hospitalized, Days 7, 14, 28, 42, 84, and 114, at end of treatment, and up to 1 month post treatment

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Voriconazole: 2 to <12 Years	Voriconazole: 12 to <18 Years
Arm/Group Description	Participants aged 2 to less than (<)12 years (and young adolescents aged 12 to 14 years weighing <50 kilograms [kg]) received a loading dose of voriconazole of 9 milligrams per kg (mg/kg), intravenously (IV), every 12 hours (q12h) for the first 24 hours, followed by maintenance dosing of 8 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral (PO) therapy and received 9 mg/kg PO voriconazole q12h for a maximum dose of 350 mg.	Participants aged 12 to <18 years (excluding those aged 12-14 years weighing <50 kg) received a loading dose of 6 mg/kg IV q12h for the first 24 hours followed by maintenance dosing of 4 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral therapy and received 200-300 mg PO q12h.
Measure Participants	11	20
With AEs	11 100%	19 95%
With serious AEs	6 54.5%	9 45%
With severe AEs	5 45.5%	8 40%
Discontinued treatment due to AEs	1 9.1%	0 0%
Dose reduced or temporarily discontinued due to AE	0 0%	4 20%

2. Secondary Outcome

Title	Percentage of Participants With a Global Response of Success
Description	Percentage of participants with global response of success at Weeks 6 and at EOT (up to Week 12). Global response of success was defined as a participant who achieved a complete or partial global response per the investigator. Complete response was defined as resolution of all clinical signs and symptoms PLUS resolution of 90 percent (%) or more of the lesions visible on radiological studies and attributed to invasive aspergillosis (IA) at Baseline. Partial response was defined as clinical improvement PLUS 50% to <90% resolution of the radiological lesions attributed to IA at Baseline.
Time Frame	Weeks 6 and End of Treatment (EOT; up to Week 12)

Outcome Measure Data

Analysis Population Description

Modified intent to treat (MITT) population: all participants receiving at least 1 dose of study drug and diagnosed with proven or probable aspergillosis (defined by modified European Organization for Research and Treatment of Cancer Mycoses Study Group [EORTC/MSC] criteria) or microbiologically confirmed scedosporium or fusarium infection.

Arm/Group Title	Voriconazole: 2 to <12 Years	Voriconazole: 12 to <18 Years
Arm/Group Description	Participants aged 2 to less than (<)12 years (and young adolescents aged 12 to 14 years weighing <50 kilograms [kg]) received a loading dose of voriconazole of 9 milligrams per kg (mg/kg), intravenously (IV), every 12 hours (q12h) for the first 24 hours, followed by maintenance dosing of 8 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral (PO) therapy and received 9 mg/kg PO voriconazole q12h for a maximum dose of 350 mg.	Participants aged 12 to <18 years (excluding those aged 12-14 years weighing <50 kg) received a loading dose of 6 mg/kg IV q12h for the first 24 hours followed by maintenance dosing of 4 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral therapy and received 200-300 mg PO q12h.
Measure Participants	5	9
Week 6	40.0 363.6%	77.8 389%
EOT	40.0 363.6%	77.8 389%

3. Secondary Outcome

Title	All-Cause Mortality - Number of Participant Deaths
Description	Number of participant deaths reported at Week 6 and at EOT (up to Week 12).
Time Frame	Week 6 and EOT (up to Week 12)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Voriconazole: 2 to <12 Years	Voriconazole: 12 to <18 Years
Arm/Group Description	Participants aged 2 to less than (<)12 years (and young adolescents aged 12 to 14 years weighing <50 kilograms [kg]) received a loading dose of voriconazole of 9 milligrams per kg (mg/kg), intravenously (IV), every 12 hours (q12h) for the first 24 hours, followed by maintenance dosing of 8 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral (PO) therapy and received 9 mg/kg PO voriconazole q12h for a maximum dose of 350 mg.	Participants aged 12 to <18 years (excluding those aged 12-14 years weighing <50 kg) received a loading dose of 6 mg/kg IV q12h for the first 24 hours followed by maintenance dosing of 4 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral therapy and received 200-300 mg PO q12h.
Measure Participants	11	20
Week 6	3 27.3%	1 5%
EOT	0 0%	1 5%

4. Secondary Outcome

Title	Attributable Mortality - Number of Participant Deaths
Description	Number of participant deaths attributable to study drug reported at Week 6 and at EOT (up to Week 12).
Time Frame	Weeks 6 and EOT (up to Week 12)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Voriconazole: 2 to <12 Years	Voriconazole: 12 to <18 Years
Arm/Group Description	Participants aged 2 to less than (<)12 years (and young adolescents aged 12 to 14 years weighing <50 kilograms [kg]) received a loading dose of voriconazole of 9 milligrams per kg (mg/kg), intravenously (IV), every 12 hours (q12h) for the first 24 hours, followed by maintenance dosing of 8 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral (PO) therapy and received 9 mg/kg PO voriconazole q12h for a maximum dose of 350 mg.	Participants aged 12 to <18 years (excluding those aged 12-14 years weighing <50 kg) received a loading dose of 6 mg/kg IV q12h for the first 24 hours followed by maintenance dosing of 4 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral therapy and received 200-300 mg PO q12h.
Measure Participants	11	20
Number [participants]	0 0%	0 0%

5. Secondary Outcome

Title	Time to Death
Time Frame	Baseline up to 1 month post treatment

Outcome Measure Data

Analysis Population Description

Safety population; only participants who died were included in the analysis.

Arm/Group Title	Voriconazole: 2 to <12 Years	Voriconazole: 12 to <18 Years
Arm/Group Description	Participants aged 2 to less than (<)12 years (and young adolescents aged 12 to 14 years weighing <50 kilograms [kg]) received a loading dose of voriconazole of 9 milligrams per kg (mg/kg), intravenously (IV), every 12 hours (q12h) for the first 24 hours, followed by maintenance dosing of 8 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral (PO) therapy and received 9 mg/kg PO voriconazole q12h for a maximum dose of 350 mg.	Participants aged 12 to <18 years (excluding those aged 12-14 years weighing <50 kg) received a loading dose of 6 mg/kg IV q12h for the first 24 hours followed by maintenance dosing of 4 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral therapy and received 200-300 mg PO q12h.
Measure Participants	3	2
Median (Full Range) [days]	30.0	47.5

Adverse Events

Adverse Event Reporting Description	The same event may appear as both an adverse event (AE) and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	Voriconazole: 2 to <12 Years		Voriconazole: 12 to <18 Years
Arm/Group Description	Participants aged 2 to less than (<)12 years (and young adolescents aged 12 to 14 years weighing <50 kilograms [kg]) received a loading dose of voriconazole of 9 milligrams per kg (mg/kg), intravenously (IV), every 12 hours (q12h) for the first 24 hours, followed by maintenance dosing of 8 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral (PO) therapy and received 9 mg/kg PO voriconazole q12h for a maximum dose of 350 mg.		Participants aged 12 to <18 years (excluding those aged 12-14 years weighing <50 kg) received a loading dose of 6 mg/kg IV q12h for the first 24 hours followed by maintenance dosing of 4 mg/kg IV q12h for a minimum of 7 days of IV therapy. Once significant clinical improvement was observed, participants could have been switched or oral therapy and received 200-300 mg PO q12h.
All Cause Mortality
	Voriconazole: 2 to <12 Years		Voriconazole: 12 to <18 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Voriconazole: 2 to <12 Years		Voriconazole: 12 to <18 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/11 (54.5%)		9/20 (45%)
Blood and lymphatic system disorders
Coagulopathy	0/11 (0%)		1/20 (5%)
Febrile neutropenia	1/11 (9.1%)		2/20 (10%)
Neutropenia	1/11 (9.1%)		0/20 (0%)
Thrombocytopenia	0/11 (0%)		1/20 (5%)
Cardiac disorders
Cardiac arrest	1/11 (9.1%)		0/20 (0%)
Cardiac failure congestive	0/11 (0%)		1/20 (5%)
Eye disorders
Visual impairment	0/11 (0%)		1/20 (5%)
Gastrointestinal disorders
Gingival bleeding	0/11 (0%)		1/20 (5%)
Lower gastrointestinal haemorrhage	1/11 (9.1%)		0/20 (0%)
Small intestinal haemorrhage	0/11 (0%)		1/20 (5%)
Upper gastrointestinal haemorrhage	0/11 (0%)		1/20 (5%)
Hepatobiliary disorders
Drug-induced liver injury	0/11 (0%)		1/20 (5%)
Infections and infestations
Aspergillosis	1/11 (9.1%)		0/20 (0%)
Pneumonia	0/11 (0%)		1/20 (5%)
Sepsis	1/11 (9.1%)		1/20 (5%)
Septic shock	2/11 (18.2%)		2/20 (10%)
Metabolism and nutrition disorders
Hypoglycaemia	1/11 (9.1%)		0/20 (0%)
Hypokalaemia	1/11 (9.1%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Muscular weakness	0/11 (0%)		1/20 (5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia	0/11 (0%)		2/20 (10%)
Nervous system disorders
Loss of consciousness	0/11 (0%)		1/20 (5%)
Renal and urinary disorders
Renal failure acute	1/11 (9.1%)		1/20 (5%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/11 (0%)		1/20 (5%)
Pulmonary oedema	0/11 (0%)		1/20 (5%)
Respiratory failure	0/11 (0%)		1/20 (5%)
Surgical and medical procedures
Endotracheal intubation	0/11 (0%)		1/20 (5%)
Vascular disorders
Aneurysm ruptured	1/11 (9.1%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	Voriconazole: 2 to <12 Years		Voriconazole: 12 to <18 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/11 (90.9%)		19/20 (95%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	0/11 (0%)		1/20 (5%)
Febrile neutropenia	0/11 (0%)		2/20 (10%)
Lymphadenitis	1/11 (9.1%)		0/20 (0%)
Lymphopenia	0/11 (0%)		1/20 (5%)
Neutropenia	1/11 (9.1%)		0/20 (0%)
Neutrophilia	0/11 (0%)		1/20 (5%)
Pancytopenia	1/11 (9.1%)		0/20 (0%)
Thrombocytopenia	1/11 (9.1%)		2/20 (10%)
Cardiac disorders
Tachycardia	0/11 (0%)		1/20 (5%)
Ear and labyrinth disorders
Ear haemorrhage	1/11 (9.1%)		0/20 (0%)
Tinnitus	0/11 (0%)		1/20 (5%)
Eye disorders
Abnormal sensation in eye	0/11 (0%)		1/20 (5%)
Asthenopia	0/11 (0%)		1/20 (5%)
Cataract	0/11 (0%)		1/20 (5%)
Chromatopsia	0/11 (0%)		1/20 (5%)
Conjunctival haemorrhage	1/11 (9.1%)		0/20 (0%)
Conjunctivitis	0/11 (0%)		2/20 (10%)
Diplopia	0/11 (0%)		1/20 (5%)
Dry eye	1/11 (9.1%)		0/20 (0%)
Eye discharge	1/11 (9.1%)		0/20 (0%)
Eye irritation	0/11 (0%)		1/20 (5%)
Eye pain	0/11 (0%)		1/20 (5%)
Photophobia	1/11 (9.1%)		1/20 (5%)
Vision blurred	0/11 (0%)		3/20 (15%)
Visual impairment	0/11 (0%)		1/20 (5%)
Gastrointestinal disorders
Abdominal distension	0/11 (0%)		1/20 (5%)
Abdominal pain	0/11 (0%)		3/20 (15%)
Abdominal pain upper	0/11 (0%)		1/20 (5%)
Anal fissure	0/11 (0%)		1/20 (5%)
Constipation	1/11 (9.1%)		1/20 (5%)
Diarrhoea	3/11 (27.3%)		1/20 (5%)
Dysphagia	0/11 (0%)		1/20 (5%)
Flatulence	0/11 (0%)		1/20 (5%)
Gastritis	0/11 (0%)		1/20 (5%)
Gastrooesophageal reflux disease	0/11 (0%)		1/20 (5%)
Haematemesis	0/11 (0%)		1/20 (5%)
Lip dry	1/11 (9.1%)		0/20 (0%)
Mouth haemorrhage	1/11 (9.1%)		1/20 (5%)
Mouth ulceration	1/11 (9.1%)		2/20 (10%)
Nausea	0/11 (0%)		2/20 (10%)
Painful defaecation	1/11 (9.1%)		0/20 (0%)
Proctalgia	1/11 (9.1%)		0/20 (0%)
Rectal haemorrhage	0/11 (0%)		1/20 (5%)
Upper gastrointestinal haemorrhage	1/11 (9.1%)		0/20 (0%)
Vomiting	1/11 (9.1%)		1/20 (5%)
General disorders
Catheter site discharge	0/11 (0%)		1/20 (5%)
Catheter site pain	1/11 (9.1%)		2/20 (10%)
Fatigue	0/11 (0%)		1/20 (5%)
Infusion site pain	0/11 (0%)		1/20 (5%)
Local swelling	0/11 (0%)		1/20 (5%)
Mucosal inflammation	0/11 (0%)		3/20 (15%)
Oedema peripheral	0/11 (0%)		2/20 (10%)
Pain	0/11 (0%)		2/20 (10%)
Pyrexia	0/11 (0%)		7/20 (35%)
Hepatobiliary disorders
Jaundice cholestatic	0/11 (0%)		1/20 (5%)
Infections and infestations
Anal abscess	0/11 (0%)		1/20 (5%)
Bacteraemia	0/11 (0%)		1/20 (5%)
Bronchitis	0/11 (0%)		1/20 (5%)
Cytomegalovirus infection	1/11 (9.1%)		0/20 (0%)
Device related infection	0/11 (0%)		1/20 (5%)
Implant site pustules	1/11 (9.1%)		0/20 (0%)
Paronychia	0/11 (0%)		1/20 (5%)
Postoperative wound infection	1/11 (9.1%)		0/20 (0%)
Sinusitis	0/11 (0%)		2/20 (10%)
Staphylococcal bacteraemia	0/11 (0%)		1/20 (5%)
Staphylococcal infection	0/11 (0%)		1/20 (5%)
Systemic candida	0/11 (0%)		1/20 (5%)
Upper respiratory tract infection	3/11 (27.3%)		1/20 (5%)
Viral upper respiratory tract infection	0/11 (0%)		1/20 (5%)
Injury, poisoning and procedural complications
Allergic transfusion reaction	1/11 (9.1%)		1/20 (5%)
Contusion	0/11 (0%)		2/20 (10%)
Excoriation	0/11 (0%)		2/20 (10%)
Incorrect drug administration rate	1/11 (9.1%)		0/20 (0%)
Procedural pain	2/11 (18.2%)		2/20 (10%)
Investigations
Activated partial thromboplastin time prolonged	1/11 (9.1%)		0/20 (0%)
Alanine aminotransferase increased	0/11 (0%)		2/20 (10%)
Aspartate aminotransferase increased	0/11 (0%)		1/20 (5%)
Blood bilirubin increased	0/11 (0%)		1/20 (5%)
Blood creatinine increased	1/11 (9.1%)		1/20 (5%)
Blood phosphorus decreased	1/11 (9.1%)		0/20 (0%)
Blood potassium increased	0/11 (0%)		1/20 (5%)
Blood pressure increased	0/11 (0%)		1/20 (5%)
Blood uric acid increased	0/11 (0%)		1/20 (5%)
Cardiac murmur	1/11 (9.1%)		0/20 (0%)
Liver function test abnormal	0/11 (0%)		2/20 (10%)
Oxygen saturation decreased	0/11 (0%)		1/20 (5%)
Prothrombin time prolonged	1/11 (9.1%)		0/20 (0%)
Respirovirus test positive	0/11 (0%)		1/20 (5%)
Transaminases increased	0/11 (0%)		2/20 (10%)
Weight decreased	0/11 (0%)		1/20 (5%)
Metabolism and nutrition disorders
Fluid overload	0/11 (0%)		1/20 (5%)
Fluid retention	0/11 (0%)		1/20 (5%)
Hypercalcaemia	0/11 (0%)		1/20 (5%)
Hyperkalaemia	0/11 (0%)		2/20 (10%)
Hyperuricaemia	0/11 (0%)		1/20 (5%)
Hypoalbuminaemia	1/11 (9.1%)		1/20 (5%)
Hypocalcaemia	3/11 (27.3%)		0/20 (0%)
Hypokalaemia	1/11 (9.1%)		3/20 (15%)
Hypomagnesaemia	2/11 (18.2%)		1/20 (5%)
Hyponatraemia	2/11 (18.2%)		0/20 (0%)
Hypophosphataemia	3/11 (27.3%)		0/20 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/11 (9.1%)		0/20 (0%)
Back pain	0/11 (0%)		3/20 (15%)
Muscle spasms	0/11 (0%)		1/20 (5%)
Myalgia	1/11 (9.1%)		1/20 (5%)
Neck pain	0/11 (0%)		1/20 (5%)
Pain in extremity	1/11 (9.1%)		2/20 (10%)
Pain in jaw	1/11 (9.1%)		0/20 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Leukaemia	0/11 (0%)		1/20 (5%)
Nervous system disorders
Central nervous system lesion	0/11 (0%)		1/20 (5%)
Dizziness	0/11 (0%)		3/20 (15%)
Headache	1/11 (9.1%)		2/20 (10%)
Lethargy	0/11 (0%)		2/20 (10%)
Paraesthesia	0/11 (0%)		1/20 (5%)
Somnolence	0/11 (0%)		1/20 (5%)
Psychiatric disorders
Affect lability	0/11 (0%)		1/20 (5%)
Depression	1/11 (9.1%)		0/20 (0%)
Insomnia	0/11 (0%)		2/20 (10%)
Renal and urinary disorders
Dysuria	0/11 (0%)		1/20 (5%)
Pollakiuria	0/11 (0%)		1/20 (5%)
Renal failure	0/11 (0%)		1/20 (5%)
Urinary retention	0/11 (0%)		1/20 (5%)
Reproductive system and breast disorders
Genital swelling	1/11 (9.1%)		0/20 (0%)
Vulvar erosion	1/11 (9.1%)		0/20 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	0/11 (0%)		1/20 (5%)
Cough	2/11 (18.2%)		2/20 (10%)
Dyspnoea	0/11 (0%)		2/20 (10%)
Epistaxis	2/11 (18.2%)		4/20 (20%)
Haemoptysis	0/11 (0%)		1/20 (5%)
Hypoxia	0/11 (0%)		1/20 (5%)
Nasal congestion	1/11 (9.1%)		2/20 (10%)
Oropharyngeal pain	0/11 (0%)		2/20 (10%)
Pharyngeal inflammation	0/11 (0%)		1/20 (5%)
Rales	1/11 (9.1%)		0/20 (0%)
Tachypnoea	0/11 (0%)		2/20 (10%)
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/11 (9.1%)		0/20 (0%)
Dermatitis allergic	1/11 (9.1%)		0/20 (0%)
Dermatitis contact	1/11 (9.1%)		0/20 (0%)
Dermatitis exfoliative	0/11 (0%)		1/20 (5%)
Dry skin	0/11 (0%)		1/20 (5%)
Ecchymosis	1/11 (9.1%)		0/20 (0%)
Erythema	0/11 (0%)		1/20 (5%)
Heat rash	0/11 (0%)		1/20 (5%)
Hyperhidrosis	1/11 (9.1%)		0/20 (0%)
Ingrowing nail	0/11 (0%)		1/20 (5%)
Petechiae	0/11 (0%)		1/20 (5%)
Pigmentation disorder	0/11 (0%)		1/20 (5%)
Post inflammatory pigmentation change	1/11 (9.1%)		0/20 (0%)
Pruritus	0/11 (0%)		1/20 (5%)
Rash	0/11 (0%)		1/20 (5%)
Rash macular	1/11 (9.1%)		1/20 (5%)
Rash maculo-papular	2/11 (18.2%)		1/20 (5%)
Red man syndrome	1/11 (9.1%)		0/20 (0%)
Scab	0/11 (0%)		1/20 (5%)
Skin burning sensation	1/11 (9.1%)		0/20 (0%)
Skin lesion	1/11 (9.1%)		0/20 (0%)
Toxic skin eruption	1/11 (9.1%)		0/20 (0%)
Urticaria	0/11 (0%)		1/20 (5%)
Vascular disorders
Flushing	0/11 (0%)		1/20 (5%)
Haematoma	0/11 (0%)		1/20 (5%)
Haemorrhage	0/11 (0%)		1/20 (5%)
Hypertension	0/11 (0%)		1/20 (5%)
Hypotension	0/11 (0%)		1/20 (5%)
Phlebitis	0/11 (0%)		1/20 (5%)

Limitations/Caveats

The study was prematurely terminated due to slow enrollment. The study was not terminated due to any safety issues or concerns. Interpretation of the data are limited due to the small sample size and descriptive design.

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Certain Agreements

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

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.