Trial Outcomes & Findings for Study Of The Pharmacokinetics And Safety Of Voriconazole In Children 2 To 11 Years Old Who Are At High Risk For Systemic Fungal Infection (NCT NCT00739934)

Last Updated: 2011-01-28

Results Overview

AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose

Results posted on

2011-01-28

Participant Flow

Participant milestones

Participant milestones
Measure	All Participants Voriconazole intravenous (IV) multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 1 to 7 (up to Day 20 or more if clinically indicated). The oral maintenance dosing regimen (200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
Voriconazole IV STARTED	40
Voriconazole IV COMPLETED	34
Voriconazole IV NOT COMPLETED	6
Voriconazole Oral STARTED	34
Voriconazole Oral COMPLETED	31
Voriconazole Oral NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants Voriconazole intravenous (IV) multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 1 to 7 (up to Day 20 or more if clinically indicated). The oral maintenance dosing regimen (200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
Voriconazole IV Adverse Event	6
Voriconazole Oral Other	3

Baseline Characteristics

Study Of The Pharmacokinetics And Safety Of Voriconazole In Children 2 To 11 Years Old Who Are At High Risk For Systemic Fungal Infection

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=40 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 1 to 7 (up to Day 20 or more if clinically indicated). The oral maintenance dosing regimen (200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
Age, Customized 2 to <6 years	24 Participants n=5 Participants
Age, Customized 6 to <12 years	16 Participants n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	23 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose

Population: Intent-to treat (ITT) population of participants who had completed pharmacokinetic (PK) blood sampling for at least one day. N = number of participants with analyzable data.

AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=36 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Area Under the Curve Over Dosing Interval at Steady State (AUC12,ss) Following IV Administration	21.42 μg*h/mL Standard Deviation 35.05

PRIMARY outcome

Timeframe: Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=36 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Peak Plasma Concentration at Steady State (Cmax,ss) Following IV Administration	4.26 μg/mL Standard Deviation 3.73

PRIMARY outcome

Timeframe: Day 7 (up to Day 20 or more) at predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=36 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Time to Reach Cmax (Tmax) Following IV Administration	2.30 hours Interval 1.0 to 4.07

PRIMARY outcome

Timeframe: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=33 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
AUC12,ss Following Oral Administration	18.64 μg*h/mL Standard Deviation 50.63

PRIMARY outcome

Timeframe: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=33 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Cmax,ss Following Oral Administration	3.62 μg/mL Standard Deviation 4.66

PRIMARY outcome

Timeframe: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=33 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Tmax Following Oral Administration	1.07 hours Interval 0.73 to 8.03

SECONDARY outcome

Timeframe: Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

AUC12 = Area under the plasma concentration-time profile from time zero (predose) to twelve hours. AUC12 was obtained by the Linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=33 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
AUC12 Following IV Loading Dose	7.85 μg*h/mL Standard Deviation 6.71

SECONDARY outcome

Timeframe: Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=33 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Cmax Following an IV Loading Dose	2.15 μg/mL Standard Deviation 1.10

SECONDARY outcome

Timeframe: Day 1 predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=33 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Tmax Following an IV Loading Dose	2.30 hours Interval 1.72 to 4.08

SECONDARY outcome

Timeframe: Day 7 (up to Day 20 or more) for IV; Day 7 (or later) for oral at predose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data; n = number of participants who contributed to data.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=36 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Trough Concentrations (Cmin) IV Day 7 (up to Day 20) (n=36)	0.61 μg/mL Standard Deviation 2.56
Trough Concentrations (Cmin) Oral Day 7 (up to Day 30) (n=32)	0.52 μg/mL Standard Deviation 3.32

SECONDARY outcome

Timeframe: Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=39 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration Day 1	20.98 μg*h/mL Standard Deviation 8.05
AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration Day 7 (up to Day 20)	41.95 μg*h/mL Standard Deviation 14.30

SECONDARY outcome

Timeframe: Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=39 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration Day 1	2.97 μg/mL Standard Deviation 0.94
Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration Day 7 (up to Day 20)	4.47 μg/mL Standard Deviation 1.44

SECONDARY outcome

Timeframe: Days 1 and 7 (up to Day 20 or more) predose, 60 and 138 minutes, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N=number of participants with analyzable data.

Zero Tmax refers to the highest concentration observed for one participant at predose. The profile of the metabolite is relatively flat, which could result in slight variation in sample collection or assay process.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=39 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration Day 1	4.00 hours Interval 1.72 to 8.0
Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following IV Administration Day 7 (up to Day 20)	4.00 hours Interval 0.0 to 12.05

SECONDARY outcome

Timeframe: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

AUC12,ss = Area under the plasma concentration-time profile from time zero (predose) to twelve hours at steady-state. AUC12,ss was obtained by the Linear/Log trapezoidal method.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=33 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
AUC12,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration	51.65 μg*h/mL Standard Deviation 27.88

SECONDARY outcome

Timeframe: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=33 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Cmax,ss of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration	5.62 μg/mL Standard Deviation 2.54

SECONDARY outcome

Timeframe: Day 7 (or later) predose, 1, 2, 4, 6, 8 and 12 hours postdose

Population: ITT population of participants who had completed PK blood sampling for at least one day. N = number of participants with analyzable data.

Outcome measures

Outcome measures
Measure	Voriconazole IV n=33 Participants Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 2 to 7 (up to Day 20 or more if clinically indicated).
Tmax of N-oxide Voriconazole Metabolite (UK-121, 265) Following Oral Administration	3.97 hours Interval 0.92 to 8.03

Adverse Events

Voriconazole IV

Serious events: 6 serious events

Other events: 39 other events

Deaths: 0 deaths

Voriconazole Oral

Serious events: 13 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER

Measure	Voriconazole IV n=40 participants at risk Voriconazole IV multiple dose (7 mg/kg once every 12 hours) was administered in the morning and evening on Days 1 to 7 (up to Day 20 or more if clinically indicated).	Voriconazole Oral n=34 participants at risk Voriconazole oral maintenance dosing regimen (200 mg every 12 hours) was administered following voriconazole IV in the morning and evening and lasted 6.5 days (up to Day 30 if clinically indicated).
Gastrointestinal disorders Abdominal pain	0.00% 0/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Diarrhoea	0.00% 0/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Catheter related complication	0.00% 0/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	14.7% 5/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Immune system disorders Acute graft versus host disease in skin	0.00% 0/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cellulitis	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Central line infection	0.00% 0/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Cytomegalovirus infection	0.00% 0/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Enterobacter bacteraemia	0.00% 0/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Infections and infestations Enterobacter sepsis	0.00% 0/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Device migration	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Transplant failure	0.00% 0/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Alanine aminotransferase increased	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Aspartate aminotransferase increased	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Cytomegalovirus test	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Investigations Hepatic enzyme increased	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Nervous system disorders Reversible posterior leukoencephalopathy syndrome	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Renal failure	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	2.9% 1/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Hypotension	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Vascular disorders Venoocclusive disease	2.5% 1/40 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.	0.00% 0/34 The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.