Trial Outcomes & Findings for Canadian Cardiology de Novo Study: A Comparison Between Tacrolimus- and Cyclosporine- Based Immunoprophylactic Regimens (NCT NCT00157014)

NCT ID: NCT00157014

Last Updated: 2017-06-05

Results Overview

The markers assessed were p-ERK ½ (phosphorylated extracellular signal-regulated kinase), p-JNK (phosphorylated jun N-terminal kinase) and p-p38 MAPK (phosphorylated mitogen-activated protein kinase). The data for each biopsy marker were expressed as a ratio of its densitometry / densitometry of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Change is defined as Week 52 assessment- Week 2 assessment.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 111 participants
• Primary outcome timeframe: 2 Weeks and 52 Weeks
• Results posted on: 2017-06-05

Participant Flow

• 3 patients randomized to cyclosporine actually received tacrolimus and were included in the Treatment Exposure Population for tacrolimus. * 2 patients randomized for tacrolimus were excluded from Treatment Exposure Population - 1 never received drug; 1 received incorrect drug without a waiver.

Participant milestones

Measure	Tacrolimus - Adult Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Tacrolimus - Pediatric Pediatrics: 0.05 - 0.30 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant	Cyclosporine - Pediatric Pediatrics: 6 - 10 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
Overall Study STARTED	52	46	5	6
Overall Study COMPLETED	45	41	4	5
Overall Study NOT COMPLETED	7	5	1	1

Reasons for withdrawal

Measure	Tacrolimus - Adult Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Tacrolimus - Pediatric Pediatrics: 0.05 - 0.30 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant	Cyclosporine - Pediatric Pediatrics: 6 - 10 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
Overall Study Death	4	2	1	1
Overall Study Physician Decision	0	1	0	0
Overall Study Medications withdrawn on family request	0	1	0	0
Overall Study Patient withdrawn by investigator	1	0	0	0
Overall Study Patient unable to return in nursing home	1	0	0	0
Overall Study Patient would not receive transplant	0	1	0	0
Overall Study Withdrawal by Subject	1	0	0	0

Baseline Characteristics

Canadian Cardiology de Novo Study: A Comparison Between Tacrolimus- and Cyclosporine- Based Immunoprophylactic Regimens

Baseline characteristics by cohort

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Tacrolimus - Pediatric n=5 Participants Pediatrics: 0.05 - 0.30 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant	Cyclosporine - Pediatric n=6 Participants Pediatrics: 6 - 10 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant	Total n=109 Participants Total of all reporting groups
Age, Customized 0 - ˂ 2 Years	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Age, Customized 2 - 10 Years	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Age, Customized 10 - ˂ 18 Years	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	6 Participants n=21 Participants
Age, Customized 18 - 49 Years	14 Participants n=5 Participants	18 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	32 Participants n=21 Participants
Age, Customized 50 - 59 Years	18 Participants n=5 Participants	15 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	33 Participants n=21 Participants
Age, Customized 60 - 69 Years	18 Participants n=5 Participants	12 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	30 Participants n=21 Participants
Age, Customized 70 Years and Older	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Sex/Gender, Customized Male	43 Participants n=5 Participants	37 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	82 Participants n=21 Participants
Sex/Gender, Customized Female	9 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	27 Participants n=21 Participants
Race/Ethnicity, Customized European descent/ White	48 Participants n=5 Participants	40 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	97 Participants n=21 Participants
Race/Ethnicity, Customized Black	2 Participants n=5 Participants	4 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	7 Participants n=21 Participants
Race/Ethnicity, Customized East Indian	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Latin American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Aboriginal	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants

PRIMARY outcome

Timeframe: 2 Weeks and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

The markers assessed were p-ERK ½ (phosphorylated extracellular signal-regulated kinase), p-JNK (phosphorylated jun N-terminal kinase) and p-p38 MAPK (phosphorylated mitogen-activated protein kinase).

The data for each biopsy marker were expressed as a ratio of its densitometry / densitometry of glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

Change is defined as Week 52 assessment- Week 2 assessment.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies p-ERK ½ - Week 2	0.70 Densitometry / Densitometry of GAPDH Standard Deviation 0.500	0.90 Densitometry / Densitometry of GAPDH Standard Deviation 0.641
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies p-ERK ½ - Week 52	0.87 Densitometry / Densitometry of GAPDH Standard Deviation 0.539	0.79 Densitometry / Densitometry of GAPDH Standard Deviation 0.674
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies p-ERK ½ - Change from Week 2	0.05 Densitometry / Densitometry of GAPDH Standard Deviation 0.834	-0.05 Densitometry / Densitometry of GAPDH Standard Deviation 0.662
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies p-JNK - Week 2	1.10 Densitometry / Densitometry of GAPDH Standard Deviation 0.813	1.23 Densitometry / Densitometry of GAPDH Standard Deviation 0.722
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies p-JNK - Week 52	1.33 Densitometry / Densitometry of GAPDH Standard Deviation 0.890	1.46 Densitometry / Densitometry of GAPDH Standard Deviation 0.792
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies p-JNK - Change from Week 2	0.03 Densitometry / Densitometry of GAPDH Standard Deviation 1.188	0.22 Densitometry / Densitometry of GAPDH Standard Deviation 0.957
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies p-p38 MAPK - Week 2	0.48 Densitometry / Densitometry of GAPDH Standard Deviation 0.450	0.54 Densitometry / Densitometry of GAPDH Standard Deviation 0.556
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies p-p38 MAPK - Week 52	0.63 Densitometry / Densitometry of GAPDH Standard Deviation 0.664	0.77 Densitometry / Densitometry of GAPDH Standard Deviation 0.717
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies p-p38 MAPK - Change from Week 2	0.14 Densitometry / Densitometry of GAPDH Standard Deviation 0.733	0.23 Densitometry / Densitometry of GAPDH Standard Deviation 0.828

PRIMARY outcome

Timeframe: 2 Weeks and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

The markers assessed were p-ERK ½, p-JNK and p-p38 MAPK.

The data for each biopsy marker were expressed as a ratio of its densitometry / densitometry of glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

Change is defined as Week 52 assessment- Week 2 assessment.

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population) p-ERK ½ - Week 2	1.74 Densitometry / Densitometry of GAPDH Standard Deviation 0.972	1.67 Densitometry / Densitometry of GAPDH Standard Deviation 0.682
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population) p-ERK ½ - Week 52	0.93 Densitometry / Densitometry of GAPDH Standard Deviation 0.184	1.22 Densitometry / Densitometry of GAPDH Standard Deviation 0.633
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population) p-ERK ½ - Change from Week 2	-0.09 Densitometry / Densitometry of GAPDH Standard Deviation 0	-0.27 Densitometry / Densitometry of GAPDH Standard Deviation 0.309
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population) p-JNK - Week 2	1.17 Densitometry / Densitometry of GAPDH Standard Deviation 0.420	0.91 Densitometry / Densitometry of GAPDH Standard Deviation 0.430
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population) p-JNK - Week 52	0.57 Densitometry / Densitometry of GAPDH Standard Deviation 0.085	0.82 Densitometry / Densitometry of GAPDH Standard Deviation 0.537
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population) p-JNK - Change from Week 2	-0.21 Densitometry / Densitometry of GAPDH Standard Deviation 0	0.04 Densitometry / Densitometry of GAPDH Standard Deviation 0.189
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population) p-p38 MAPK - Week 2	0.83 Densitometry / Densitometry of GAPDH Standard Deviation 0.467	0.43 Densitometry / Densitometry of GAPDH Standard Deviation 0.364
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population) p-p38 MAPK - Week 52	0.24 Densitometry / Densitometry of GAPDH Standard Deviation 0.014	0.58 Densitometry / Densitometry of GAPDH Standard Deviation 0.432
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population) p-p38 MAPK - Change from Week 2	-0.04 Densitometry / Densitometry of GAPDH Standard Deviation 0	0.34 Densitometry / Densitometry of GAPDH Standard Deviation 0.630

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

MCP-1= monocyte chemoattractant protein-1

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: MCP-1 Pre-Transplant	233.05 pg/mL Standard Deviation 292.832	193.63 pg/mL Standard Deviation 144.696
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: MCP-1 Week 52	229.96 pg/mL Standard Deviation 263.084	180.90 pg/mL Standard Deviation 145.067
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: MCP-1 Change from Pre-Transplant at Week 52	42.92 pg/mL Standard Deviation 165.517	-16.49 pg/mL Standard Deviation 126.586

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

s-ICAM= soluble-intracellular adhesion molecule

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: s-ICAM Pre-Transplant	766.58 ng/mL Standard Deviation 449.572	674.46 ng/mL Standard Deviation 429.036
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: s-ICAM Week 52	590.30 ng/mL Standard Deviation 369.942	503.71 ng/mL Standard Deviation 305.531
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: s-ICAM Change from Pre-Transplant at Week 52	-227.58 ng/mL Standard Deviation 366.136	-183.96 ng/mL Standard Deviation 250.382

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: E-selectin Pre-Transplant	90.40 ng/mL Standard Deviation 72.801	98.96 ng/mL Standard Deviation 89.153
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: E-selectin Week 52	68.60 ng/mL Standard Deviation 51.911	80.93 ng/mL Standard Deviation 70.383
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: E-selectin Change from Pre-Transplant at Week 52	-18.58 ng/mL Standard Deviation 48.247	-19.16 ng/mL Standard Deviation 52.080

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Homocysteine Pre-Transplant	14.2 μmol/L Standard Deviation 6.94	15.9 μmol/L Standard Deviation 6.97
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Homocysteine Week 52	13.5 μmol/L Standard Deviation 4.19	15.8 μmol/L Standard Deviation 5.33
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Homocysteine Change from Pre-Transplant at Week 52	0.3 μmol/L Standard Deviation 5.02	0.7 μmol/L Standard Deviation 7.61

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

hsCRP= high-sensitivity C Reactive Protein

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: hsCRP Pre-Transplant	32.85 mg/L Standard Deviation 50.859	21.83 mg/L Standard Deviation 33.547
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: hsCRP Week 52	3.01 mg/L Standard Deviation 3.313	3.95 mg/L Standard Deviation 5.273
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: hsCRP Change from Pre-Transplant at Week 52	-34.32 mg/L Standard Deviation 54.257	-18.69 mg/L Standard Deviation 35.354

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: F2 Isoprostanes Pre-Transplant	52.03 pg/mL Standard Deviation 76.090	53.94 pg/mL Standard Deviation 78.476
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: F2 Isoprostanes Week 52	30.08 pg/mL Standard Deviation 25.905	50.44 pg/mL Standard Deviation 68.416
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: F2 Isoprostanes Change from Pre-Transplant at Week 52	-13.29 pg/mL Standard Deviation 40.543	-3.43 pg/mL Standard Deviation 103.457

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

T-bars = thiobarbituric acid reactive substances

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: T-bars Pre-Transplant	3.78 nmol/mL Standard Deviation 1.586	3.91 nmol/mL Standard Deviation 2.059
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: T-bars Week 52	3.25 nmol/mL Standard Deviation 1.365	3.14 nmol/mL Standard Deviation 1.198
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: T-bars Change from Pre-Transplant at Week 52	-0.64 nmol/mL Standard Deviation 1.724	-0.77 nmol/mL Standard Deviation 2.182

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Nitrotyrosine Pre-Transplant	422.63 nM Standard Deviation 393.554	482.43 nM Standard Deviation 390.702
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Nitrotyrosine Week 52	451.88 nM Standard Deviation 443.372	368.95 nM Standard Deviation 262.693
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Nitrotyrosine Change from Pre-Transplant at Week 52	71.44 nM Standard Deviation 332.351	-99.79 nM Standard Deviation 228.268

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

GSH/GSSG= ratio of reduced to oxidised glutathione

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: GSH/GSSG Pre-Transplant	55.07 Ratio Standard Deviation 62.780	58.83 Ratio Standard Deviation 71.289
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: GSH/GSSG Week 52	51.69 Ratio Standard Deviation 55.721	53.72 Ratio Standard Deviation 55.264
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: GSH/GSSG Change from Pre-Transplant at Week 52	-2.07 Ratio Standard Deviation 70.036	-5.55 Ratio Standard Deviation 80.490

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

BNP= Brain Natriuretic Peptide

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: BNP Pre-Transplant	4314.8 ng/L Standard Deviation 4861.78	4240.8 ng/L Standard Deviation 4673.72
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: BNP Week 52	670.1 ng/L Standard Deviation 1053.21	1856.8 ng/L Standard Deviation 5077.26
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: BNP Change from Pre-Transplant at Week 52	-4018.4 ng/L Standard Deviation 5043.28	-1446.7 ng/L Standard Deviation 6460.33

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Troponin T Pre-Transplant	0.30 ug/L Standard Deviation 0.686	0.28 ug/L Standard Deviation 0.878
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Troponin T Week 52	0.03 ug/L Standard Deviation 0.116	0.04 ug/L Standard Deviation 0.120
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Troponin T Change from Pre-Transplant at Week 52	-0.32 ug/L Standard Deviation 0.768	-0.27 ug/L Standard Deviation 0.958

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Osteopontin Pre-Transplant	11.88 ng/mL Standard Deviation 9.528	11.14 ng/mL Standard Deviation 12.278
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Osteopontin Week 52	8.77 ng/mL Standard Deviation 10.462	10.49 ng/mL Standard Deviation 8.987
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Osteopontin Change from Pre-Transplant at Week 52	-2.22 ng/mL Standard Deviation 10.615	0.20 ng/mL Standard Deviation 11.158

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Fibrinogen Pre-Transplant	4.4 g/L Standard Deviation 1.27	4.4 g/L Standard Deviation 1.23
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Fibrinogen Week 52	3.4 g/L Standard Deviation 0.87	3.8 g/L Standard Deviation 0.77
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Fibrinogen Change from Pre-Transplant at Week 52	-1.1 g/L Standard Deviation 1.48	-0.5 g/L Standard Deviation 1.23

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

IL= Interleukin

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-6 Pre-Transplant	3.36 pg/mL Standard Deviation 4.221	2.54 pg/mL Standard Deviation 3.159
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-6 Week 52	0.98 pg/mL Standard Deviation 0.743	0.90 pg/mL Standard Deviation 0.651
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-6 Change from Pre-Transplant at Week 52	-2.84 pg/mL Standard Deviation 4.635	-1.56 pg/mL Standard Deviation 3.146

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-18 Pre-Transplant	574.0 pg/mL Standard Deviation 291.89	496.2 pg/mL Standard Deviation 246.90
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-18 Week 52	534.6 pg/mL Standard Deviation 290.38	427.2 pg/mL Standard Deviation 217.07
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-18 Change from Pre-Transplant at Week 52	5.2 pg/mL Standard Deviation 289.66	-71.0 pg/mL Standard Deviation 243.81

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Cystatin-C Pre-Transplant	1.21 mg/L Standard Deviation 0.414	1.29 mg/L Standard Deviation 0.490
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Cystatin-C Week 52	1.29 mg/L Standard Deviation 0.533	1.48 mg/L Standard Deviation 0.714
Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Cystatin-C Change from Pre-Transplant at Week 52	0.06 mg/L Standard Deviation 0.464	0.27 mg/L Standard Deviation 0.744

SECONDARY outcome

Timeframe: 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Acute rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

Patients may report more than one acute rejection.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria Total Acute Rejection Episodes	8 Rejection Episodes	8 Rejection Episodes
Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria Acute Rejection Episodes with ISHLT Grade ≥3A	3 Rejection Episodes	7 Rejection Episodes
Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria Acute Rejection Episodes w/ Hemodynamic Compromise	6 Rejection Episodes	2 Rejection Episodes

SECONDARY outcome

Timeframe: 52 Weeks

Population: The population analyzed represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation. Only participants who experienced acute rejection were included in the analysis.

Acute Rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

Time to first acute rejection is defined as: date of onset - date of transplant.

Outcome measures

Measure	Tacrolimus - Adult n=6 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=8 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Time to First Acute Rejection Episode Following de Novo Cardiac Transplant	55.0 Days Standard Deviation 35.60	35.60 Days Standard Deviation 132.86

SECONDARY outcome

Timeframe: 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Severe Acute Rejection is defined as rejection with ISHLT Grade 4.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Number of Patients Requiring Antilymphocyte Antibodies or Steroids for Treatment of Severe Acute Rejection	0 Patients	0 Patients

SECONDARY outcome

Timeframe: 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population - defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

The number of rejection episodes requiring treatment (medications started/ stopped, non-medication treatment, or both) regardless of biopsy grade or presence of hemodynamic compromise.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Number of Cardiac Rejection Episodes Requiring Treatment	12 Rejection Episodes	11 Rejection Episodes

SECONDARY outcome

Timeframe: 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population - defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

MCAR represents the average number of acute rejections among all patients in each treatment group. Results were based on rejection episodes with endomyocardial biopsies.

Acute rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Mean Cases of Acute Rejection (MCAR) Per Patient	0.15 MCAR per patient Standard Deviation 0.46	0.17 MCAR per patient Standard Deviation 0.38

SECONDARY outcome

Timeframe: 26 Weeks and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population - defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

A successful steroid taper or withdrawal was defined as steroids (prednisone) being discontinued or tapered to the suggested dose level after week 26.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Number of Patients With Successful Steroid Taper or Withdrawal at Weeks 26 and 52 Week 26	22 Patients	16 Patients
Number of Patients With Successful Steroid Taper or Withdrawal at Weeks 26 and 52 Week 52	33 Patients	29 Patients

SECONDARY outcome

Timeframe: 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population - defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Treatment failure was defined as death, re-transplantation, withdrawal due to an Adverse Event, or a switch of main immunosuppressant medication, whichever came first.

Crossover was defined as a switch from originally administered primary immunosuppressant (tacrolimus or cyclosporine) to the alternate primary immunosuppressant.

Outcome measures

Measure	Tacrolimus - Adult n=52 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Number of Patients With Treatment Failure and Crossover for Treatment Failure Treatment Failures	6 Patients	11 Patients
Number of Patients With Treatment Failure and Crossover for Treatment Failure Crossover for Treatment Failures	2 Patients	8 Patients

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population - defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation and Oxidation: F2 Isoprostanes (Pediatric Population) Pre-Transplant	106.06 pg/mL Standard Deviation 37.974	104.68 pg/mL Standard Deviation 53.812
Changes in Circulating Markers of Inflammation and Oxidation: F2 Isoprostanes (Pediatric Population) Week 52	69.71 pg/mL Standard Deviation 38.620	66.48 pg/mL Standard Deviation 33.298
Changes in Circulating Markers of Inflammation and Oxidation: F2 Isoprostanes (Pediatric Population) Change from Pre-Transplant at Week 52	-38.31 pg/mL Standard Deviation 47.563	-30.07 pg/mL Standard Deviation 80.246

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population - defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation and Oxidation: Nitrotyrosine (Pediatric Population) Pre-Transplant	233.08 nM Standard Deviation 211.491	12701.21 nM Standard Deviation 21666.231
Changes in Circulating Markers of Inflammation and Oxidation: Nitrotyrosine (Pediatric Population) Week 52	5462.99 nM Standard Deviation 7988.134	41147.62 nM Standard Deviation 37565.740
Changes in Circulating Markers of Inflammation and Oxidation: Nitrotyrosine (Pediatric Population) Change from Pre-Transplant at Week 52	5148.42 nM Standard Deviation 7849.554	21514.62 nM Standard Deviation 49626.968

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population - defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation and Oxidation: hsCRP (Pediatric Population) Pre-Transplant	30.46 mg/L Standard Deviation 32.274	12.08 mg/L Standard Deviation 14.771
Changes in Circulating Markers of Inflammation and Oxidation: hsCRP (Pediatric Population) Week 52	26.31 mg/L Standard Deviation 45.109	2.43 mg/L Standard Deviation 1.348
Changes in Circulating Markers of Inflammation and Oxidation: hsCRP (Pediatric Population) Change from Pre-Transplant at Week 52	-7.85 mg/L Standard Deviation 78.126	-13.94 mg/L Standard Deviation 16.461

SECONDARY outcome

Timeframe: Pre-Transplant and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population - defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Change is defined as Week 52 assessment - Pre-Transplant assessment

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Changes in Circulating Markers of Inflammation and Oxidation: Cystatin-C (Pediatric Population) Pre-Transplant	0.86 mg/L Standard Deviation 0.248	0.77 mg/L Standard Deviation 0.194
Changes in Circulating Markers of Inflammation and Oxidation: Cystatin-C (Pediatric Population) Week 52	0.87 mg/L Standard Deviation 0.133	0.84 mg/L Standard Deviation 0.111
Changes in Circulating Markers of Inflammation and Oxidation: Cystatin-C (Pediatric Population) Change from Pre-Transplant at Week 52	-0.11 mg/L Standard Deviation 0.197	-0.01 mg/L Standard Deviation 0.108

SECONDARY outcome

Timeframe: 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Acute rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

Patients may report more than one rejection episode.

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria (Pediatric Population) Total Acute Rejection Episodes	3 Rejection Episodes	3 Rejection Episodes
Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria (Pediatric Population) Acute Rejection Episodes with ISHLT Grade ≥3A	3 Rejection Episodes	3 Rejection Episodes
Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria (Pediatric Population) Acute Rejection Episodes w/ Hemodynamic Compromise	0 Rejection Episodes	0 Rejection Episodes

SECONDARY outcome

Timeframe: 52 Weeks

Population: The population analyzed represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation. Only participants who experienced acute rejection were included in the analysis.

Acute Rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

Time to first acute rejection is defined as: date of onset - date of transplant.

Outcome measures

Measure	Tacrolimus - Adult n=3 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=3 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Time to First Acute Rejection Episode Following de Novo Cardiac Transplant (Pediatric Population)	56.3 Days Standard Deviation 27.06	49.0 Days Standard Deviation 15.62

SECONDARY outcome

Timeframe: 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Severe Acute Rejection was defined as rejection with ISHLT Grade 4.

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Number of Patients Requiring Antilymphocyte Antibodies or Steroids for Treatment of Severe Acute Rejection (Pediatric Population)	0 Patients	0 Patients

SECONDARY outcome

Timeframe: 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

A summary of rejection episodes requiring treatment regardless of biopsy grade or presence of hemodynamic compromise.

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Number of Cardiac Rejection Episodes Requiring Treatment (Pediatric Population)	3 Rejection Episodes	3 Rejection Episodes

SECONDARY outcome

Timeframe: 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population- defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

MCAR represents the average number of acute rejections among all patients in each treatment group. Results were based on rejection episodes with endomyocardial biopsies.

Acute rejection was defined as a rejection with ISHLT Grade ≥3A or by the presence of hemodynamic compromise.

ISHLT Grades ≥3A include: Multifocal Moderate Rejection; Diffuse, Borderline Severe Acute Rejection; and Severe Acute Rejection.

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Mean Cases of Acute Rejection (MCAR) Per Patient (Pediatric Population)	0.60 MCAR per patient Standard Deviation 0.55	0.50 MCAR per patient Standard Deviation 0.55

SECONDARY outcome

Timeframe: 26 Weeks and 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population - defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

A successful steroid taper or withdrawal was defined as steroids (prednisone) being discontinued or tapered to the suggested dose level after week 26.

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Number of Patients With Successful Steroid Taper or Withdrawal at Weeks 26 and 52 (Pediatric Population) Week 26	2 Patients	3 Patients
Number of Patients With Successful Steroid Taper or Withdrawal at Weeks 26 and 52 (Pediatric Population) Week 52	1 Patients	1 Patients

SECONDARY outcome

Timeframe: 52 Weeks

Population: The number of participants analyzed per arm represents Treatment Exposure Population - defined as all patients receiving at least 1 dose of study medication summarized according to treatment received regardless of randomization allocation.

Treatment failure was defined as death, re-transplantation, withdrawal due to an Adverse Event, or a switch of main immunosuppressant medication, whichever came first.

Crossover was defined as a switch from originally administered primary immunosuppressant (tacrolimus or cyclosporine) to the alternate primary immunosuppressant.

Outcome measures

Measure	Tacrolimus - Adult n=5 Participants Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=6 Participants Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
Number of Patients With Treatment Failure and Crossover for Treatment Failure (Pediatric Population) Treatment Failures	1 Patients	3 Patients
Number of Patients With Treatment Failure and Crossover for Treatment Failure (Pediatric Population) Crossover for Treatment Failures	0 Patients	3 Patients

Adverse Events

Tacrolimus - Adult

Serious events: 21 serious events

Other events: 52 other events

Deaths: 0 deaths

Cyclosporine - Adult

Serious events: 24 serious events

Other events: 46 other events

Deaths: 0 deaths

Tacrolimus - Pediatric

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Cyclosporine - Pediatric

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tacrolimus - Adult n=52 participants at risk Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 participants at risk Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Tacrolimus - Pediatric n=5 participants at risk Pediatrics: 0.05 - 0.30 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant	Cyclosporine - Pediatric n=6 participants at risk Pediatrics: 6 - 10 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoproliferative disorder	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Cerebral infarction	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Cerebrovascular accident	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Convulsion	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	33.3% 2/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Depressed level of consciousness	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Encephalopathy	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Hydrocephalus	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Partial seizures	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Syncope vasovagal	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Blood and lymphatic system disorders Neutropenia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Blood and lymphatic system disorders Pancytopenia	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Atrial flutter	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Atrioventricular block complete	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Cardiac arrest	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Cardiac failure congestive	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Cardiogenic shock	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Pericardial effusion	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Pericarditis constrictive	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Right ventricular failure	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Supraventricular tachycardia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Cardiac tamponade	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Ear and labyrinth disorders Deafness unilateral	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Endocrine disorders Adrenal mass	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Eye disorders Blindness cortical	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Abdominal pain	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Constipation	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Diarrhoea	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Dysphagia	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Gastrointestinal haemorrhage	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Mouth ulceration	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Pancreatic disorder	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Vomiting	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Catheter related complication	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Chest pain	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Chills	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Oedema peripheral	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Pyrexia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Hepatobiliary disorders Cholelithiasis	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Immune system disorders Heart transplant rejection	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Immune system disorders Transplant rejection	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations American trypanosomiasis	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Bronchopneumonia	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Cellulitis	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Clostridium difficile colitis	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Cystitis	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Cytomegalovirus gastritis	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Cytomegalovirus infection	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Diverticulitis	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Klebsiella bacteraemia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Lobar pneumonia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Lung infection	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Mediastinitis	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Pneumonia	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Pyelonephritis acute	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Sepsis	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Sinusitis	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Staphylococcal infection	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Viral infection	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Pneumonia klebsiella	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Injury, poisoning and procedural complications Haemothorax	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Injury, poisoning and procedural complications Post procedural haematoma	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Injury, poisoning and procedural complications Wound dehiscence	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Fluid overload	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Arthralgia	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer stage III	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastrointestinal carcinoma	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Tension headache	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Cerebral haemorrhage	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Psychiatric disorders Confusional state	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Renal and urinary disorders Nephropathy toxic	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Renal and urinary disorders Renal failure	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Renal and urinary disorders Renal failure acute	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Renal and urinary disorders Renal impairment	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Non-cardiogenic pulmonary oedema	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Respiratory alkalosis	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Skin and subcutaneous tissue disorders Acne	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Vascular disorders Deep vein thrombosis	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Vascular disorders Inferior vena caval occlusion	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Vascular disorders Orthostatic hypotension	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Vascular disorders Temporal arteritis	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Vascular disorders Vascular pseudoaneurysm	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.

Other adverse events

Measure	Tacrolimus - Adult n=52 participants at risk Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Cyclosporine - Adult n=46 participants at risk Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant	Tacrolimus - Pediatric n=5 participants at risk Pediatrics: 0.05 - 0.30 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant	Cyclosporine - Pediatric n=6 participants at risk Pediatrics: 6 - 10 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
Skin and subcutaneous tissue disorders Skin lesion	13.5% 7/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Skin and subcutaneous tissue disorders Skin ulcer	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Surgical and medical procedures Removal of foreign body	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Vascular disorders Hypertension	40.4% 21/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	56.5% 26/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	60.0% 3/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	66.7% 4/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Vascular disorders Hypotension	25.0% 13/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	15.2% 7/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Skin and subcutaneous tissue disorders Rash	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Nausea	15.4% 8/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	32.6% 15/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Vomiting	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	19.6% 9/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	40.0% 2/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Blood and lymphatic system disorders Aneamia	34.6% 18/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	32.6% 15/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	33.3% 2/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Blood and lymphatic system disorders Leukocytosis	17.3% 9/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	19.6% 9/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Blood and lymphatic system disorders Leukopenia	23.1% 12/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	19.6% 9/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Blood and lymphatic system disorders Thrombocytopenia	9.6% 5/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Blood and lymphatic system disorders Neutropenia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Atelectasis	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Atrial fibrillation	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Atrial flutter	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Bradycardia	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Fluid overload	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	13.0% 6/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Mitral valve incompetence	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Oedema due to cardiac disease	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Oedema peripheral	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	30.4% 14/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Palpitations	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	13.0% 6/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Pericardial effusion	9.6% 5/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	13.0% 6/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Pulmonary oedema	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Right ventricular dysfunction	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Tricuspid valve incompetence	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Cardiac disorders Arrhythmia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Congenital, familial and genetic disorders Becker's muscular dystrophy	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Eye disorders Amblyopia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Abdominal distension	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Abdominal pain	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	10.9% 5/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Abdominal pain upper	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Constipation	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	28.3% 13/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Diarrhoea	50.0% 26/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	17.4% 8/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Dysphagia	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Gingival hyperplasia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Mouth ulceration	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Gastritis	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Gingival hypertrophy	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	50.0% 3/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Gastrointestinal disorders Tooth discolouration	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Asthenia	9.6% 5/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Chest pain	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Chills	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Fatigue	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	15.2% 7/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Hyperthermia	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Influenza like illness	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Oedema peripheral	26.9% 14/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	13.0% 6/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	33.3% 2/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Pyrexia	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	33.3% 2/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
General disorders Oedema	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	40.0% 2/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Hepatobiliary disorders Hyperbilirubinaemia	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Immune system disorders Transplant rejection	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Bronchitis	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Diverticulitis	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Influenza	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Nasopharyngitis	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	13.0% 6/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Pneumonia	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Sinusitis	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Staphylococcal infection	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Upper respiratory tract infection	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	13.0% 6/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	33.3% 2/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Urinary tract infection	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Adenovirus infection	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Clostridial infection	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Gastroenteritis	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Lower respiratory tract infection	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Oral herpes	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Otitis media	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Tooth abscess	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Viral upper repiratory tract infection	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Infections and infestations Wound infection pseudomonas	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Injury, poisoning and procedural complications Incision site pain	9.6% 5/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Injury, poisoning and procedural complications Joint sprain	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Injury, poisoning and procedural complications Wound	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Investigations Blood creatinine increased	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	10.9% 5/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Investigations Cardiac murmur	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Investigations Hepatic enzyme increased	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Investigations Weight decreased	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Investigations Weight increased	19.2% 10/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	19.6% 9/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Investigations Cytomegalovirus antigen positive	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Investigations Epstein-Barr virus antibody positive	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Investigations Glomerular filtration rate decreased	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Investigations White blood cell count increased	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Diabetes mellitus	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	23.9% 11/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Dyslipidaemia	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Fluid overload	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	40.0% 2/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Gout	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	10.9% 5/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Hyperglycaemia	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Hyperkalaemia	9.6% 5/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	15.2% 7/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	33.3% 2/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Hyperlipidaemia	9.6% 5/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	17.4% 8/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Hypoglycaemia	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Hypokalaemia	15.4% 8/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	13.0% 6/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	40.0% 2/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	33.3% 2/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Hypomagnesaemia	25.0% 13/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	40.0% 2/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	33.3% 2/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Hypovolaemia	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Metabolism and nutrition disorders Fluid retention	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Arthralgia	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	10.9% 5/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Back pain	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	10.9% 5/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Muscle spasms	15.4% 8/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	17.4% 8/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	3.8% 2/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	13.5% 7/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	4.3% 2/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Myalgia	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	13.0% 6/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Musculoskeletal and connective tissue disorders Pain in extremity	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Convulsion	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Dizziness	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Headache	21.2% 11/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	28.3% 13/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Hypoaesthesia	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Paraesthesia	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Tremor	44.2% 23/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	28.3% 13/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Nervous system disorders Syncope	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Psychiatric disorders Agitation	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Psychiatric disorders Anxiety	9.6% 5/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	10.9% 5/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Psychiatric disorders Confusional state	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	2.2% 1/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Psychiatric disorders Depression	11.5% 6/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	10.9% 5/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Psychiatric disorders Insomnia	15.4% 8/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	26.1% 12/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	16.7% 1/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Renal and urinary disorders Renal failure	21.2% 11/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	26.1% 12/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Renal and urinary disorders Renal failure acute	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Renal and urinary disorders Renal failure chronic	5.8% 3/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Renal and urinary disorders Renal impairment	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	6.5% 3/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Cough	17.3% 9/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	13.0% 6/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.4% 8/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	10.9% 5/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Pleural effusion	19.2% 10/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	39.1% 18/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Pneumothorax	9.6% 5/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	20.0% 1/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Skin and subcutaneous tissue disorders Acne	7.7% 4/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	13.0% 6/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.
Skin and subcutaneous tissue disorders Hypertrichosis	1.9% 1/52 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	8.7% 4/46 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	0.00% 0/5 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.	50.0% 3/6 • After the initiation of study drug up to 30 days after the last dose of study drug. Treatment Emergent Adverse Events were reported. Within a preferred term, patients were counted once.

Additional Information

Associate Director, Scientific Affairs

Astellas Pharma Canada, Inc

Email: clinicaltrials@us.astellas.com

Results disclosure agreements

• Principal investigator is a sponsor employee Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document. Sponsor may delay the publication for an additional 60 days to seek patent protection.
• Publication restrictions are in place

Restriction type: OTHER