Study of CMX001 to Prevent/Control Cytomegalovirus Infection in R+ Hematopoietic Stem Cell Transplant Recipients

• Sponsor: Chimerix (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00942305
• Collaborator: (none)
• Enrollment: 239
• Locations: 26
• Arms: 2
• Actual Duration (Months): 27
• Patients Per Site: 9.2
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This was a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study of brincidofovir (BCV) administered orally once or twice weekly for up to 11 weeks. Dosing was initiated immediately following engraftment (between Days 14-30 post-transplant) to prevent/control cytomegalovirus (CMV) infection or prevent disease in R+ hematopoietic stem cell transplant (HCT) recipients.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infection	Drug: Brincidofovir; Drug: Placebo	Phase 2

Detailed Description

This was to be a 2-part study. Part 1 was a randomized, double-blind, placebo-controlled, dose-escalation study of multiple doses of oral brincidofovir (BCV) in R+ hematopoietic stem cell transplant (HCT) recipients. In Part 2, one of the dose levels administered in Part 1 was to be tested against placebo to evaluate the statistical significance of BCV as a therapy for preventing progression of cytomegalovirus (CMV) infection or preventing CMV disease. The first 3 dose-escalating cohorts in Part 1 were to include 32 subjects within each cohort (24 randomized to receive oral BCV and 8 randomized to receive placebo in a 3:1 ratio) for a total of 96 planned subjects. Following completion of the first 3 cohorts and subsequent safety review of the data, up to an additional 3 cohorts of 32 subjects each could have been enrolled. Two additional cohorts (labeled Cohort 4 and Cohort 4A) beyond the initial 3 cohorts were actually enrolled in Part 1 of the study. Following the safety and antiviral activity analyses of the 5 cohorts in Part 1 and the number of subjects enrolled in each of those cohorts, Part 2 of the study was not conducted.

Study Design

• Study Type: Interventional
• Actual Enrollment: 239 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Dose-escalation Study of the Safety, Tolerability and Ability of CMX001 to Prevent or Control CMV Infection in R+ Hematopoietic Stem Cell Transplant Recipients
• Actual Study Start Date: Oct 1, 2009
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Cohort 1 = 40 mg of matching placebo administered once weekly (QW) Cohort 2 = 100 mg of matching placebo administered QW Cohort 3 = 200 mg of matching placebo administered QW Cohort 4 = 200 mg of matching placebo administered twice weekly (BIW) Cohort 4A = 100 mg of matching placebo administered BIW	Drug: Placebo; Subjects received their first dose of study drug within 30 (+5) days post-transplant and were treated through Week 13 post-transplant. Matching placebo administered for each cohort.
Experimental: Brincidofovir Cohort 1 = 40 mg brincidofovir (BCV) administered once weekly (QW) Cohort 2 = 100 mg BCV administered QW Cohort 3 = 200 mg BCV administered QW Cohort 4 = 200 mg BCV administered twice weekly (BIW) Cohort 4A = 100 mg BCV administered BIW	Drug: Brincidofovir; Subjects received their first dose of study drug of brincidofovir (BCV) within 30 (+5) days post-transplant and were treated through Week 13 post-transplant.; Other Names: BCV CMX001

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinically Significant CMV Infection [Randomization to Week 8 post-treatment (~19 weeks)]

   The primary efficacy endpoint was a binomial outcome of failure to prevent cytomegalovirus (CMV) infection defined as CMV DNAemia >200 copies/mL obtained at the time of the last treatment with study drug or diagnosis of CMV disease at some point during the treatment phase.

Eligibility Criteria

Criteria

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

Inclusion Criteria

For inclusion into the study, all prospective subjects were required to fulfill all of the following criteria (as applicable):

1. Were aged ≥18 years. Males must have been able and willing to use adequate contraceptive methods throughout the treatment and follow-up phases of the study.

2. Were cytomegalovirus (CMV) seropositive before allogeneic hematopoietic stem cell transplantation (HCT) (i.e., R+ subjects).

3. Were less than 30 days post qualifying transplant.

4. Had evidence of engraftment before randomization and receiving their first dose of study drug.

5. Were able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant gastrointestinal [GI] events).

6. Were willing and able to understand and provide written informed consent.

7. To the best of his or her knowledge, were willing and able to participate in all required study activities for the duration of the study.

Exclusion Criteria

Subjects meeting any of the following exclusion criteria were to be excluded from participation in the study:

1. Females who were pregnant or currently nursing.

2. Had a body mass index >35 kg/m2. [Note: This criterion was removed per Protocol Amendment 2 dated 27 August 2010.]

3. Had hypersensitivity to cidofovir (CDV) or brincidofovir.

4. Recipients for whom the current, predose clinical course of CMV infection suggested that the investigator would not be able to withhold treatment for CMV for a minimum of 5, but preferably 7 days following the subject's first dose of study drug.

5. Received any of the following:

• Ganciclovir, valganciclovir, foscarnet or CDV within 14 days prior to enrollment;

• Any anti-CMV therapy following transplantation (including Cytogam®1);

• Any CMV vaccine;

• Any investigational drug with antiviral activity against double-stranded DNA (dsDNA) viruses within 14 days prior to enrollment. [Note: An investigational drug was defined as a drug that was not approved for any indication by the Food and Drug Administration.]; or

• Any other investigational drug (i.e., those without any "anti-dsDNA virus" activity; e.g., anti-influenza compounds) within 14 days prior to enrollment without the prior written consent of the medical monitor. The use of investigational drugs in certain circumstances was added per Protocol Amendment 1 dated 15 January 2010.

1. Received high dose acyclovir (>2000 mg total oral daily dose or >5 mg/kg intravenously 3 times daily) or valacyclovir (Valtrex; >3000 mg total daily dose) at the time of dosing.

2. Were diagnosed with active CMV disease within 6 months prior to enrollment; patients with CMV DNAemia requiring intervention with antiviral therapy at the time of enrollment.

3. Were HIV positive; patients with active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection as evidenced by plasma levels of HCV RNA or HBV DNA, respectively.

4. Received another allogeneic HCT within the past 2 years, other than the qualifying HCT.

5. Had renal insufficiency as evidenced by glomerular filtration rate (GFR) <30 mL/min.

6. Had a current diagnosis of hypotony, uveitis, or retinitis or any intraocular pathology that would predispose the subject to any one of these conditions.

7. Had hepatic dysfunction as evidenced by alanine aminotransferase or aspartate aminotransferase >5 x the upper limit of normal (ULN) or direct bilirubin >2.5 x the ULN.

8. Had any of the following active autoimmune disorders: myasthenia gravis, Addison's disease, Wegener's granulomatosis, primary biliary cirrhosis, bullous pemphigoid, autoimmune hemolytic anemia, autoimmune hepatitis, multiple sclerosis, Goodpasture's syndrome, idiopathic thrombocytopenic purpura, lupus erythematosus, dermatomyositis, polymyositis, or vasculitis.

9. Had active solid tumor malignancies with the exception of basal cell carcinoma or the condition under treatment (e.g., lymphomas).

10. Had 1 or more episode of hyperglycemic coma or diabetic ketoacidosis within the 6 months prior to enrollment.

11. Had cardiovascular disease which, in the opinion of the investigator, would interfere with the conduct of the study.

12. Had Grade 3 or 4 graft versus host disease of the GI tract; subjects with any GI disease that would, in the judgment of the investigator, preclude the subject from taking or absorbing oral medication (e.g. clinically active Crohn's disease, ischemic colitis, moderate or severe ulcerative colitis, or any condition expected to require abdominal surgery during the course of study participation).

13. Any other condition including abnormal laboratory values that would have, in the judgment of the investigator, put the subject at increased risk for participating in the trial, or interferes with the conduct of the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	Moores UCSD Cancer Center	La Jolla	California	United States	92093
3	UCLA Medical Center	Los Angeles	California	United States	90095
4	University of Colorado Denver	Aurora	Colorado	United States	80045
5	Winship Cancer Institute at Emory University	Atlanta	Georgia	United States	30322
6	University of Chicago Medical Center	Chicago	Illinois	United States	60637
7	Brigham and Womens Hospital, Division of Infectious Disease	Boston	Massachusetts	United States	02115
8	University of Michigan Medical School	Ann Arbor	Michigan	United States	48109
9	Harper University Hospital	Detroit	Michigan	United States	48201
10	University of Minnesota Medical Center	Minneapolis	Minnesota	United States	55455
11	Nebraska Medical Center	Omaha	Nebraska	United States	68198-5130
12	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
13	Montefiore Medical Center Oncology	Bronx	New York	United States	10467
14	Mt. Sinai School of Medicine	New York	New York	United States	10029
15	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
16	University of Rochester Medical Center	Rochester	New York	United States	14642
17	UNC Health Care Center	Chapel Hill	North Carolina	United States	27599
18	Duke University Medical Center	Durham	North Carolina	United States	27710
19	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27517
20	The Cleveland Clinic	Cleveland	Ohio	United States	44195
21	Oregon Health and Science University	Portland	Oregon	United States	97239
22	Baylor University Medical Center	Dallas	Texas	United States	75246
23	UT Southwestern Medical Center at Dallas	Dallas	Texas	United States	75390-8565
24	University of Texas, MD Anderson Cancer Center	Houston	Texas	United States	77030
25	Utah Cancer Specialists - Intermountain Healthcare	Salt Lake City	Utah	United States	84088
26	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Chimerix

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• CMX001 to Prevent Cytomegalovirus Disease in Hematopoietic-Cell Transplantation
• Analysis of Mutations in Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis

Publications

• Lanier ER, Foster S, Brundage T, Chou S, Prichard MN, Kleiboeker S, Wilson C, Colville D, Mommeja-Marin H. Analysis of Mutations in the Gene Encoding Cytomegalovirus DNA Polymerase in a Phase 2 Clinical Trial of Brincidofovir Prophylaxis. J Infect Dis. 2016 Jul 1;214(1):32-5. doi: 10.1093/infdis/jiw073. Epub 2016 Mar 3.

• Responsible Party: Chimerix
• ClinicalTrials.gov Identifier: NCT00942305
• Other Study ID Numbers: CMX001-201
• First Posted: Jul 20, 2009
• Last Update Posted: Jul 16, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Chimerix: Allogeneic stem cell transplant; CMV seropositive (R+); transplant
• Additional relevant MeSH terms: Infections; Communicable Diseases; Cytomegalovirus Infections; Brincidofovir

Study Results

Participant Flow

Recruitment Details	Note: While a total of 239 subjects were enrolled, 1 center was excluded from analysis due to concerns about investigator/site compliance with the study protocol. This center had enrolled 9 subjects: 5 subjects who received brincidofovir (BCV) in Cohort 1, 2 subjects who received placebo in Cohort 1, and 2 subjects who received BCV in Cohort 2.

Arm/Group Title	Cohort 1 BCV	Cohort 1 Placebo	Cohort 2 BCV	Cohort 2 Placebo	Cohort 3 BCV	Cohort 3 Placebo	Cohort 4 BCV	Cohort 4 Placebo	Cohort 4a	Cohort 4a Placebo
Arm/Group Description	40 mg brincidofovir (BCV) administered once weekly	Placebo administered once weekly (QW)	100 mg brincidofovir (BCV) administered once weekly	Placebo administered once weekly (QW)	200 mg brincidofovir (BCV) administered once weekly	Placebo administered once weekly (QW)	200 mg brincidofovir (BCV) administered twice weekly (BIW) Note: This dose was reduced to 200 mg BCV once weekly for ongoing subjects in this cohort following the recommendation of the Data and Safety Monitoring Board. No new subjects were enrolled into this cohort following the decision to reduce the dose.	Placebo administered twice weekly (BIW)	100 mg brincidofovir (BCV) administered twice weekly (BIW)	Placebo administered twice weekly (BIW)
Period Title: Overall Study
STARTED	30	10	29	10	39	14	30	10	50	17
COMPLETED	7	5	14	4	14	9	6	5	25	7
NOT COMPLETED	23	5	15	6	25	5	24	5	25	10

Baseline Characteristics

Arm/Group Title	Cohort 1 BCV	Cohort 1 Placebo	Cohort 2 BCV	Cohort 2 Placebo	Cohort 3 BCV	Cohort 3 Placebo	Cohort 4 BCV	Cohort 4 Placebo	Cohort 4a BCV	Cohort 4a Placebo	Total
Arm/Group Description	40 mg brincidofovir (BCV) administered once weekly (QW)	Placebo administered once weekly (QW)	100 mg brincidofovir (BCV) administered once weekly (QW)	Placebo administered once weekly (QW)	200 mg brincidofovir (BCV) administered once weekly (QW)	Placebo administered once weekly (QW)	200 mg brincidofovir (BCV) administered twice weekly (BIW) Note: This dose was reduced to 200 mg BCV once weekly for ongoing subjects in this cohort following the recommendation of the Data and Safety Monitoring Board. No new subjects were enrolled into this cohort following the decision to reduce the dose.	Placebo administered twice weekly (BIW)	100 mg brincidofovir (BCV) administered twice weekly (BIW)	Placebo administered twice weekly (BIW)	Total of all reporting groups
Overall Participants	25	8	27	10	39	14	30	10	50	17	230
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.3 (10.02)	56.8 (10.12)	51.7 (10.13)	53.5 (11.08)	49.5 (12.75)	47.9 (14.05)	50.4 (11.47)	52.2 (14.76)	48.8 (12.74)	46.1 (12.14)	50.7 (12.12)
Sex: Female, Male (Count of Participants)
Female	10 40%	1 12.5%	10 37%	5 50%	17 43.6%	9 64.3%	12 40%	3 30%	24 48%	7 41.2%	98 42.6%
Male	15 60%	7 87.5%	17 63%	5 50%	22 56.4%	5 35.7%	18 60%	7 70%	26 52%	10 58.8%	132 57.4%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinically Significant CMV Infection
Description	The primary efficacy endpoint was a binomial outcome of failure to prevent cytomegalovirus (CMV) infection defined as CMV DNAemia >200 copies/mL obtained at the time of the last treatment with study drug or diagnosis of CMV disease at some point during the treatment phase.
Time Frame	Randomization to Week 8 post-treatment (~19 weeks)

Outcome Measure Data

Analysis Population Description

Modified Intent-to-Treat Population, which included all randomized subjects who took at least 1 dose of study treatment and who had at least 1 efficacy evaluation following baseline.

Arm/Group Title	Cohort 1 BCV	Cohort 1 Placebo	Cohort 2 BCV	Cohort 2 Placebo	Cohort 3 BCV	Cohort 3 Placebo	Cohort 4 BCV	Cohort 4 Placebo	Cohort 4a BCV	Cohort 4a Placebo
Arm/Group Description	40 mg brincidofovir (BCV) administered once weekly (QW)	Placebo administered once weekly (QW)	100 mg brincidofovir (BCV) administered once weekly (QW)	Placebo administered once weekly (QW)	200 mg brincidofovir (BCV) administered once weekly (QW)	Placebo administered once weekly (QW)	200 mg brincidofovir (BCV) administered twice weekly (BIW) Note: This dose was reduced to 200 mg BCV once weekly for ongoing subjects in this cohort following the recommendation of the Data and Safety Monitoring Board. No new subjects were enrolled into this cohort following the decision to reduce the dose.	Placebo administered twice weekly (BIW)	100 mg brincidofovir (BCV) administered twice weekly (BIW)	Placebo administered twice weekly (BIW)
Measure Participants	25	8	27	10	39	14	30	10	50	17
Count of Participants [Participants]	13 52%	4 50%	6 22.2%	4 40%	12 30.8%	4 28.6%	7 23.3%	3 30%	5 10%	7 41.2%

Adverse Events

Arm/Group Title	Cohort 1 BCV		Cohort 1 Placebo		Cohort 2 BCV		Cohort 2 Placebo		Cohort 3 BCV		Cohort 3 Placebo		Cohort 4 BCV		Cohort 4 Placebo		Cohort 4a BCV		Cohort 4a Placebo
Arm/Group Description	40 mg brincidofovir (BCV) administered once weekly (QW)		Placebo administered once weekly (QW)		100 mg brincidofovir (BCV) administered once weekly (QW)		Placebo administered once weekly (QW)		200 mg brincidofovir (BCV) administered once weekly (QW)		Placebo administered once weekly (QW)		200 mg brincidofovir (BCV) administered twice weekly (BIW) Note: This dose was reduced to 200 mg BCV once weekly for ongoing subjects in this cohort following the recommendation of the Data and Safety Monitoring Board. No new subjects were enrolled into this cohort following the decision to reduce the dose.		Placebo administered twice weekly (BIW)		100 mg brincidofovir (BCV) administered twice weekly (BIW)		Placebo administered twice weekly (BIW)
All Cause Mortality
	Cohort 1 BCV		Cohort 1 Placebo		Cohort 2 BCV		Cohort 2 Placebo		Cohort 3 BCV		Cohort 3 Placebo		Cohort 4 BCV		Cohort 4 Placebo		Cohort 4a BCV		Cohort 4a Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Cohort 1 BCV		Cohort 1 Placebo		Cohort 2 BCV		Cohort 2 Placebo		Cohort 3 BCV		Cohort 3 Placebo		Cohort 4 BCV		Cohort 4 Placebo		Cohort 4a BCV		Cohort 4a Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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	12/25 (48%)		4/8 (50%)		10/27 (37%)		6/10 (60%)		19/39 (48.7%)		6/14 (42.9%)		21/30 (70%)		3/10 (30%)		30/50 (60%)		8/17 (47.1%)
Blood and lymphatic system disorders
Anaemia	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Febrile neutropenia	2/25 (8%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Leukopenia	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Lymphopenia	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Neutropenia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Pancytopenia	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Thrombocytopenia	1/25 (4%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Cardiac disorders
Atrial fibrillation	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Atrial flutter	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Cardiac tamponade	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Gastrointestinal disorders
Abdominal pain	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
Colitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Constipation	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Diarrhoea	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		10/30 (33.3%)		0/10 (0%)		5/50 (10%)		1/17 (5.9%)
Diverticulum intestinal haemorrhagic	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Erosive duodenitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Gastrointestinal haemorrhage	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Nausea	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		2/30 (6.7%)		1/10 (10%)		2/50 (4%)		0/17 (0%)
Odynophagia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Vomiting	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
General disorders
Chills	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Fatigue	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Multi-organ failure	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Non-cardiac chest pain	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Pyrexia	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		2/10 (20%)		3/39 (7.7%)		0/14 (0%)		1/30 (3.3%)		2/10 (20%)		2/50 (4%)		2/17 (11.8%)
Hepatobiliary disorders
Cholecytitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Cholelithiasis	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Liver injury	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Immune system disorders
Acute graft versus host disease	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		3/39 (7.7%)		0/14 (0%)		12/30 (40%)		0/10 (0%)		15/50 (30%)		2/17 (11.8%)
Acute graft versus host disease in liver	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Acute graft versus host disease in skin	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Graft versus host disease	1/25 (4%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Hypersensitivity	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Infections and infestations
Acute graft versus host disease in intestine	1/25 (4%)		0/8 (0%)		2/27 (7.4%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Appendicitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Bacteraemia	0/25 (0%)		1/8 (12.5%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
BK virus infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Bronchiolitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Bronchopneumonia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Catheter related infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Cellulitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Citrobacter infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Clostridium difficile colitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Cytomegalovirus colitis	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Cytomegalovirus gastroenteritis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Cytomegalovirus infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Cytomegalovirus viraemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
Epstein-Barr virus infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Escherichia sepsis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Klebsiella bacteraemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Metapneumovirus infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Oral herpes	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Pneumonia	0/25 (0%)		0/8 (0%)		2/27 (7.4%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		4/50 (8%)		0/17 (0%)
Pneumonia cytomegaloviral	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Pneumonia legionella	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Pseudomonal bacteraemia	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Respiratory tract infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Sepsis	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Septic shock	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Serratia bacteraemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Staphylococcal bacteraemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		1/30 (3.3%)		0/10 (0%)		4/50 (8%)		0/17 (0%)
Staphylococcal infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Staphylococcal sepsis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Stenotrophomonas infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Streptococcal bacteraemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Viral haemorrhagic cystitis	1/25 (4%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Viral sinusitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Viral tonsillitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Injury, poisoning and procedural complications
Fall	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Hip fracture	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Skin laceration	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Transplant failure	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Investigations
Bacteria stool identified	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Liver function test abnormal	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Weight decreased	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Dehydration	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		1/50 (2%)		1/17 (5.9%)
Failure to thrive	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Hyperkalaemia	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Hyponatraemia	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Hypovolaemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Back pain	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Bone pain	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Chondrocalcinosis pyrophosphate	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Myopathy	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia recurrent	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Acute myeloid leukaemia	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Acute myeloid leukaemia recurrent	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		2/14 (14.3%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Chronic lymphocytic leukaemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Espstein-Barr virus associated lymphoproliferative disorder	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Myeloid leukaemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Non-Hodgkin's lymphoma	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
T-cell lymphoma recurrent	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Teratoma	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Nervous system disorders
Central nervous system lesion	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Cerebrovascular accident	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Cognitive disorder	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Convulsion	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Depressed level of consciousness	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Encephalopathy	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1 BCV		Cohort 1 Placebo		Cohort 2 BCV		Cohort 2 Placebo		Cohort 3 BCV		Cohort 3 Placebo		Cohort 4 BCV		Cohort 4 Placebo		Cohort 4a BCV		Cohort 4a Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	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	25/25 (100%)		8/8 (100%)		27/27 (100%)		9/10 (90%)		39/39 (100%)		14/14 (100%)		30/30 (100%)		10/10 (100%)		50/50 (100%)		17/17 (100%)
Blood and lymphatic system disorders
Anaemia	1/25 (4%)		0/8 (0%)		2/27 (7.4%)		0/10 (0%)		2/39 (5.1%)		2/14 (14.3%)		2/30 (6.7%)		1/10 (10%)		2/50 (4%)		3/17 (17.6%)
Febrile neutropenia	2/25 (8%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		1/39 (2.6%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Leukocytosis	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		3/30 (10%)		0/10 (0%)		2/50 (4%)		1/17 (5.9%)
Leukopenia	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Neutropenia	2/25 (8%)		0/8 (0%)		4/27 (14.8%)		1/10 (10%)		4/39 (10.3%)		0/14 (0%)		4/30 (13.3%)		2/10 (20%)		10/50 (20%)		4/17 (23.5%)
Pancytopenia	1/25 (4%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		1/39 (2.6%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
Thrombocytopenia	3/25 (12%)		0/8 (0%)		3/27 (11.1%)		1/10 (10%)		0/39 (0%)		1/14 (7.1%)		5/30 (16.7%)		0/10 (0%)		7/50 (14%)		2/17 (11.8%)
Haemolytic anaemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
Lymphadenopathy	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Cardiac disorders
Aortic valve incompetence	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Atrial fibrillation	1/25 (4%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Bradycardia	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Cardiomegaly	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Left ventricular hypertrophy	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Mitral valve incompetence	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Palpitations	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Tachycardia	0/25 (0%)		0/8 (0%)		0/27 (0%)		2/10 (20%)		2/39 (5.1%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		2/50 (4%)		1/17 (5.9%)
Tricuspid valve incompetence	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Ear and labyrinth disorders
Ear pain	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		2/14 (14.3%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Tinnitus	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Endocrine disorders
Adrenal insufficiency	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		2/17 (11.8%)
Eye disorders
Conjunctivitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
Dry eye	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		2/30 (6.7%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Eye pain	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Eyelid margin crusting	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Myodesopsia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Vision blurred	1/25 (4%)		0/8 (0%)		2/27 (7.4%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Vitreous detachment	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Gastrointestinal disorders
Abdominal discomfort	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		4/50 (8%)		1/17 (5.9%)
Abdominal distension	2/25 (8%)		0/8 (0%)		2/27 (7.4%)		2/10 (20%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Abdominal pain	4/25 (16%)		1/8 (12.5%)		2/27 (7.4%)		0/10 (0%)		5/39 (12.8%)		1/14 (7.1%)		11/30 (36.7%)		0/10 (0%)		13/50 (26%)		2/17 (11.8%)
Abdominal pain upper	1/25 (4%)		1/8 (12.5%)		2/27 (7.4%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		3/30 (10%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Cheilitis	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Constipation	1/25 (4%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		2/39 (5.1%)		0/14 (0%)		3/30 (10%)		0/10 (0%)		2/50 (4%)		2/17 (11.8%)
Diarrhoea	3/25 (12%)		2/8 (25%)		8/27 (29.6%)		4/10 (40%)		13/39 (33.3%)		4/14 (28.6%)		21/30 (70%)		2/10 (20%)		26/50 (52%)		4/17 (23.5%)
Dry mouth	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		2/10 (20%)		4/50 (8%)		0/17 (0%)
Dyspepsia	3/25 (12%)		1/8 (12.5%)		2/27 (7.4%)		0/10 (0%)		4/39 (10.3%)		2/14 (14.3%)		1/30 (3.3%)		0/10 (0%)		4/50 (8%)		1/17 (5.9%)
Dysphagia	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Flatulence	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		3/30 (10%)		0/10 (0%)		3/50 (6%)		1/17 (5.9%)
Gastrooesophageal reflux disease	2/25 (8%)		0/8 (0%)		4/27 (14.8%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Haemorrhoids	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Inguinal hernia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Mouth ulceration	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Nausea	6/25 (24%)		1/8 (12.5%)		5/27 (18.5%)		1/10 (10%)		11/39 (28.2%)		4/14 (28.6%)		11/30 (36.7%)		3/10 (30%)		17/50 (34%)		3/17 (17.6%)
Odynophagia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Oral disorder	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Oral pain	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Stomatitis	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Tongue coated	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Vomiting	2/25 (8%)		1/8 (12.5%)		6/27 (22.2%)		2/10 (20%)		6/39 (15.4%)		4/14 (28.6%)		8/30 (26.7%)		1/10 (10%)		22/50 (44%)		3/17 (17.6%)
Gastrointestinal haemorrhage	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Cholitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
General disorders
Adverse drug reaction	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Asthenia	3/25 (12%)		0/8 (0%)		1/27 (3.7%)		1/10 (10%)		3/39 (7.7%)		1/14 (7.1%)		2/30 (6.7%)		1/10 (10%)		1/50 (2%)		2/17 (11.8%)
Chills	1/25 (4%)		1/8 (12.5%)		0/27 (0%)		1/10 (10%)		3/39 (7.7%)		3/14 (21.4%)		0/30 (0%)		1/10 (10%)		2/50 (4%)		0/17 (0%)
Early satiety	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Face oedema	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Fatigue	1/25 (4%)		2/8 (25%)		3/27 (11.1%)		0/10 (0%)		5/39 (12.8%)		3/14 (21.4%)		0/30 (0%)		1/10 (10%)		9/50 (18%)		3/17 (17.6%)
Generalised oedema	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		3/30 (10%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Hypothermia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Non-cardiac chest pain	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		1/30 (3.3%)		1/10 (10%)		2/50 (4%)		0/17 (0%)
Oedema	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Oedema peripheral	3/25 (12%)		0/8 (0%)		5/27 (18.5%)		1/10 (10%)		3/39 (7.7%)		2/14 (14.3%)		3/30 (10%)		2/10 (20%)		8/50 (16%)		1/17 (5.9%)
Pain	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		2/50 (4%)		1/17 (5.9%)
Pyrexia	1/25 (4%)		1/8 (12.5%)		1/27 (3.7%)		3/10 (30%)		7/39 (17.9%)		1/14 (7.1%)		2/30 (6.7%)		2/10 (20%)		10/50 (20%)		4/17 (23.5%)
Multi-organ failure	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		3/39 (7.7%)		0/14 (0%)		5/30 (16.7%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Liver injury	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Immune system disorders
Acute graft versus host disease	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		4/39 (10.3%)		0/14 (0%)		24/30 (80%)		2/10 (20%)		32/50 (64%)		6/17 (35.3%)
Acute graft versus host disease in intestine	2/25 (8%)		0/8 (0%)		5/27 (18.5%)		1/10 (10%)		6/39 (15.4%)		2/14 (14.3%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Acute graft versus host disease in skin	4/25 (16%)		2/8 (25%)		3/27 (11.1%)		3/10 (30%)		7/39 (17.9%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Graft versus host disease	2/25 (8%)		1/8 (12.5%)		2/27 (7.4%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
Hypogammaglobulinaemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		1/14 (7.1%)		2/30 (6.7%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Acute graft versus host disease in liver	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Infections and infestations
Aspergillosis	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Bacteraemia	0/25 (0%)		1/8 (12.5%)		2/27 (7.4%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
BK virus infection	1/25 (4%)		0/8 (0%)		4/27 (14.8%)		1/10 (10%)		3/39 (7.7%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Candidiasis	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		1/50 (2%)		0/17 (0%)
Clostridium difficile colitis	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		1/10 (10%)		3/39 (7.7%)		0/14 (0%)		1/30 (3.3%)		1/10 (10%)		3/50 (6%)		0/17 (0%)
Cytomegalovirus colitis	0/25 (0%)		1/8 (12.5%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Cytomegalovirus infection	0/25 (0%)		0/8 (0%)		2/27 (7.4%)		2/10 (20%)		4/39 (10.3%)		2/14 (14.3%)		2/30 (6.7%)		3/10 (30%)		2/50 (4%)		1/17 (5.9%)
Cytomegalovirus viraemia	10/25 (40%)		2/8 (25%)		4/27 (14.8%)		2/10 (20%)		7/39 (17.9%)		3/14 (21.4%)		5/30 (16.7%)		0/10 (0%)		6/50 (12%)		4/17 (23.5%)
Epstein-Barr virus infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		0/50 (0%)		2/17 (11.8%)
Escherichia bacteraemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Folliculitis	0/25 (0%)		0/8 (0%)		2/27 (7.4%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		1/10 (10%)		1/50 (2%)		0/17 (0%)
Lower respiratory tract infection	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Oral candidiasis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		6/50 (12%)		1/17 (5.9%)
Otitis media	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Parainfluenzae virus infection	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Pneumonia	1/25 (4%)		0/8 (0%)		2/27 (7.4%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		5/50 (10%)		0/17 (0%)
Proctitis herpes	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Pseudomonal bacteraemia	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Staphylococcal bacteraemia	0/25 (0%)		1/8 (12.5%)		1/27 (3.7%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		1/30 (3.3%)		0/10 (0%)		6/50 (12%)		0/17 (0%)
Upper respiratory tract infection	0/25 (0%)		0/8 (0%)		2/27 (7.4%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Urinary tract infection	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		1/10 (10%)		1/39 (2.6%)		0/14 (0%)		2/30 (6.7%)		1/10 (10%)		1/50 (2%)		0/17 (0%)
Viral haemorrhagic cystitis	2/25 (8%)		1/8 (12.5%)		1/27 (3.7%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Cellulitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Escherichia sepsis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Klebsiella bacteraemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Septic shock	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Serratia bacteraemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Staphylococcal infection	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Viral tonsillitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Injury, poisoning and procedural complications
Ear abrasion	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Excoriation	0/25 (0%)		1/8 (12.5%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Fall	2/25 (8%)		0/8 (0%)		1/27 (3.7%)		1/10 (10%)		1/39 (2.6%)		1/14 (7.1%)		1/30 (3.3%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Spinal fracture	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Therapeutic agent toxicity	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Skin laceration	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Transplant failure	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Investigations
Alanine aminotransferase increased	2/25 (8%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		10/30 (33.3%)		0/10 (0%)		9/50 (18%)		1/17 (5.9%)
Aspartate aminotransferase increased	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		7/30 (23.3%)		0/10 (0%)		5/50 (10%)		1/17 (5.9%)
Blood alkaline phosphatase increased	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		1/10 (10%)		1/50 (2%)		0/17 (0%)
Blood bilirubin increased	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Blood creatinine increased	0/25 (0%)		0/8 (0%)		5/27 (18.5%)		0/10 (0%)		3/39 (7.7%)		2/14 (14.3%)		2/30 (6.7%)		0/10 (0%)		7/50 (14%)		1/17 (5.9%)
Blood lactate dehydrogenase increased	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		3/30 (10%)		0/10 (0%)		4/50 (8%)		0/17 (0%)
Blood urea increased	1/25 (4%)		0/8 (0%)		2/27 (7.4%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Blood urine present	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Cytomegalovirus test positive	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Echocardiogram abnormal	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Gamma-glutamyltransferase increased	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		3/30 (10%)		1/10 (10%)		4/50 (8%)		0/17 (0%)
Hepatic enzyme increased	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		3/39 (7.7%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		1/17 (5.9%)
Immunosuppressant drug level increased	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Liver function test abnormal	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		2/39 (5.1%)		1/14 (7.1%)		3/30 (10%)		0/10 (0%)		2/50 (4%)		1/17 (5.9%)
Neutrophil count decreased	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Platelet count decreased	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		3/39 (7.7%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Protein total increased	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Protein urine present	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Transaminases increased	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		4/50 (8%)		0/17 (0%)
Weight decreased	3/25 (12%)		0/8 (0%)		4/27 (14.8%)		0/10 (0%)		0/39 (0%)		3/14 (21.4%)		1/30 (3.3%)		2/10 (20%)		6/50 (12%)		0/17 (0%)
Metabolism and nutrition disorders
Decreased appetite	4/25 (16%)		1/8 (12.5%)		5/27 (18.5%)		1/10 (10%)		3/39 (7.7%)		1/14 (7.1%)		5/30 (16.7%)		2/10 (20%)		9/50 (18%)		2/17 (11.8%)
Dehydration	0/25 (0%)		1/8 (12.5%)		2/27 (7.4%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		1/30 (3.3%)		1/10 (10%)		4/50 (8%)		2/17 (11.8%)
Diabetes mellitus	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		1/14 (7.1%)		2/30 (6.7%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Electrolyte imbalance	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Fluid overload	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Hyperglycaemia	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		8/30 (26.7%)		0/10 (0%)		9/50 (18%)		3/17 (17.6%)
Hyperkalaemia	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		3/30 (10%)		0/10 (0%)		3/50 (6%)		1/17 (5.9%)
Hyperlipidaemia	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Hypertriglyceridaemia	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Hypoalbuminaemia	2/25 (8%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Hypocalcaemia	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		3/30 (10%)		1/10 (10%)		2/50 (4%)		0/17 (0%)
Hypoglycaemia	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Hypokalaemia	4/25 (16%)		0/8 (0%)		2/27 (7.4%)		1/10 (10%)		5/39 (12.8%)		1/14 (7.1%)		5/30 (16.7%)		2/10 (20%)		8/50 (16%)		0/17 (0%)
Hypomagnesaemia	3/25 (12%)		0/8 (0%)		3/27 (11.1%)		1/10 (10%)		2/39 (5.1%)		2/14 (14.3%)		1/30 (3.3%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Hyponatraemia	3/25 (12%)		1/8 (12.5%)		1/27 (3.7%)		0/10 (0%)		7/39 (17.9%)		1/14 (7.1%)		2/30 (6.7%)		1/10 (10%)		1/50 (2%)		0/17 (0%)
Hypophosphataemia	1/25 (4%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		2/39 (5.1%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		4/50 (8%)		1/17 (5.9%)
Malnutrition	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		1/14 (7.1%)		3/30 (10%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Vitamin D deficiency	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Failure to thrive	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/25 (0%)		0/8 (0%)		3/27 (11.1%)		1/10 (10%)		1/39 (2.6%)		1/14 (7.1%)		1/30 (3.3%)		0/10 (0%)		3/50 (6%)		1/17 (5.9%)
Back pain	0/25 (0%)		0/8 (0%)		2/27 (7.4%)		1/10 (10%)		2/39 (5.1%)		0/14 (0%)		3/30 (10%)		0/10 (0%)		4/50 (8%)		1/17 (5.9%)
Bone pain	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		2/17 (11.8%)
Bursitis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Joint swelling	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Muscle spasms	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		1/17 (5.9%)
Muscular weakness	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		4/50 (8%)		0/17 (0%)
Musculoskeletal chest pain	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Musculoskeletal discomfort	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Musculoskeletal pain	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
Myalgia	1/25 (4%)		0/8 (0%)		2/27 (7.4%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Myopathy	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		1/14 (7.1%)		2/30 (6.7%)		0/10 (0%)		2/50 (4%)		1/17 (5.9%)
Osteopenia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Pain in extremity	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		3/39 (7.7%)		3/14 (21.4%)		1/30 (3.3%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Rotator cuff syndrome	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphocytic leukaemia recurrent	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Acute myeloid leukaemia recurrent	3/25 (12%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		2/14 (14.3%)		0/30 (0%)		0/10 (0%)		3/50 (6%)		1/17 (5.9%)
Myeloid leukaemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Skin papilloma	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Chronic lymphocytic leukaemia	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Epstein-Barr virus associated lymphoproliferative disorder	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Nervous system disorders
Convulsion	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		1/39 (2.6%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Dizziness	2/25 (8%)		1/8 (12.5%)		2/27 (7.4%)		0/10 (0%)		3/39 (7.7%)		2/14 (14.3%)		3/30 (10%)		0/10 (0%)		4/50 (8%)		0/17 (0%)
Dysgeusia	1/25 (4%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		2/39 (5.1%)		1/14 (7.1%)		3/30 (10%)		0/10 (0%)		4/50 (8%)		1/17 (5.9%)
Headache	0/25 (0%)		1/8 (12.5%)		3/27 (11.1%)		0/10 (0%)		3/39 (7.7%)		2/14 (14.3%)		4/30 (13.3%)		1/10 (10%)		3/50 (6%)		3/17 (17.6%)
Hemiparesis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Paraesthesia	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Peropheral sensory neuropathy	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Peroneal nerve palsy	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		1/50 (2%)		0/17 (0%)
Tremor	3/25 (12%)		0/8 (0%)		3/27 (11.1%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		2/30 (6.7%)		1/10 (10%)		1/50 (2%)		1/17 (5.9%)
Central nervous system lesion	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Cognitive disorder	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Depressed level of consciousness	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		2/30 (6.7%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Encephalopathy	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Psychiatric disorders
Anxiety	0/25 (0%)		0/8 (0%)		3/27 (11.1%)		2/10 (20%)		3/39 (7.7%)		1/14 (7.1%)		2/30 (6.7%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Confusional state	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Depression	1/25 (4%)		1/8 (12.5%)		2/27 (7.4%)		0/10 (0%)		3/39 (7.7%)		0/14 (0%)		3/30 (10%)		2/10 (20%)		4/50 (8%)		1/17 (5.9%)
Insomnia	2/25 (8%)		0/8 (0%)		2/27 (7.4%)		0/10 (0%)		5/39 (12.8%)		1/14 (7.1%)		2/30 (6.7%)		0/10 (0%)		9/50 (18%)		0/17 (0%)
Mental status changes	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Mood altered	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Restlessness	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Renal and urinary disorders
Acute prerenal failure	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Cystitis haemorrhagic	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Dysuria	1/25 (4%)		2/8 (25%)		3/27 (11.1%)		2/10 (20%)		3/39 (7.7%)		1/14 (7.1%)		1/30 (3.3%)		1/10 (10%)		0/50 (0%)		1/17 (5.9%)
Haematuria	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
Haemorrhage urinary tract	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Hypertonic bladder	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Nocturia	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Pollakiuria	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Polyuria	0/25 (0%)		1/8 (12.5%)		1/27 (3.7%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Renal failure	1/25 (4%)		1/8 (12.5%)		2/27 (7.4%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Renal failure acute	2/25 (8%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		3/30 (10%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
Renal failure chronic	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Urinary incontinence	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		1/14 (7.1%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Cough	0/25 (0%)		0/8 (0%)		2/27 (7.4%)		2/10 (20%)		2/39 (5.1%)		1/14 (7.1%)		2/30 (6.7%)		0/10 (0%)		4/50 (8%)		2/17 (11.8%)
Dyspnoea	1/25 (4%)		1/8 (12.5%)		1/27 (3.7%)		2/10 (20%)		3/39 (7.7%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		3/50 (6%)		1/17 (5.9%)
Dyspnoea exertional	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		2/50 (4%)		2/17 (11.8%)
Epistaxis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Hypoxia	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Nasal congestion	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Oropharyngeal pain	0/25 (0%)		0/8 (0%)		2/27 (7.4%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		2/17 (11.8%)
Pleural effusion	1/25 (4%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Respiratory disorder	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Respiratory failure	0/25 (0%)		0/8 (0%)		0/27 (0%)		2/10 (20%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Rhinorrhoea	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)
Sinus congestion	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Wheezing	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Skin and subcutaneous tissue disorders
Blister	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Dermal cyst	1/25 (4%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Erythema	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		1/39 (2.6%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		4/50 (8%)		2/17 (11.8%)
Hyperkeratosis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Nail disorder	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Periorbital oedema	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Pruritus	2/25 (8%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		4/39 (10.3%)		1/14 (7.1%)		0/30 (0%)		2/10 (20%)		4/50 (8%)		1/17 (5.9%)
Rash	3/25 (12%)		2/8 (25%)		4/27 (14.8%)		2/10 (20%)		4/39 (10.3%)		1/14 (7.1%)		1/30 (3.3%)		0/10 (0%)		5/50 (10%)		3/17 (17.6%)
Rash erythematous	0/25 (0%)		1/8 (12.5%)		0/27 (0%)		0/10 (0%)		3/39 (7.7%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Rash macular	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Rash maculo-papular	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		3/50 (6%)		0/17 (0%)
Rash pruritic	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		1/10 (10%)		0/50 (0%)		0/17 (0%)
Skin erosion	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Skin exfoliation	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		1/17 (5.9%)
Skin hyperpigmentation	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		1/39 (2.6%)		0/14 (0%)		1/30 (3.3%)		0/10 (0%)		0/50 (0%)		2/17 (11.8%)
Skin irritation	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		2/30 (6.7%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Skin lesion	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		2/50 (4%)		0/17 (0%)
Surgical and medical procedures
Sinus operation	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Vascular disorders
Aortic arteriosclerosis	0/25 (0%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Deep vein thrombosis	1/25 (4%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		1/14 (7.1%)		0/30 (0%)		0/10 (0%)		0/50 (0%)		0/17 (0%)
Haematoma	0/25 (0%)		0/8 (0%)		0/27 (0%)		1/10 (10%)		0/39 (0%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		0/17 (0%)
Hypertension	0/25 (0%)		1/8 (12.5%)		2/27 (7.4%)		1/10 (10%)		4/39 (10.3%)		2/14 (14.3%)		6/30 (20%)		1/10 (10%)		6/50 (12%)		3/17 (17.6%)
Hypotension	2/25 (8%)		0/8 (0%)		0/27 (0%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		3/30 (10%)		2/10 (20%)		2/50 (4%)		0/17 (0%)
Orthostatic hypotension	0/25 (0%)		0/8 (0%)		1/27 (3.7%)		0/10 (0%)		2/39 (5.1%)		0/14 (0%)		0/30 (0%)		0/10 (0%)		1/50 (2%)		1/17 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Within 18 months after the end of the Study at all sites, if no publication of the overall multi-center results has been made, institutions are entitled to publish their locally obtained results, provided the Sponsor is given opportunity to review and comment. Institution publication may be delayed up to an additional 45 days to allow Sponsor to seek patent protection.