Trial Outcomes & Findings for Study Evaluating Refacto For Pharmacovigilance (NCT NCT00195442)

NCT ID: NCT00195442

Last Updated: 2011-02-11

Results Overview

Participants with hemophilia A suffer from a hereditary lack of blood clotting factor VIII. As a consequence, the ability of the blood to coagulate is reduced and bleedings at any site or organ of the body may occur after minor injury or even spontaneously. Predominantly, joints, muscles, and internal organs are affected by bleeding complications. Participants reported the occurrence of each bleeding episode while on study. The bleeding rate for each participant was calculated by number of reported episodes per years on study.

• Recruitment status: COMPLETED
• Target enrollment: 288 participants
• Primary outcome timeframe: Baseline up to a mean duration of 54 months
• Results posted on: 2011-02-11

Participant Flow

A total of 288 participants were observed during the study in 48 centers (44 Germany and 4 Austria) from time of First subject first visit May 1999 to Last subject last visit January 2010.

The study was terminated January 2010 due to the introduction of a successor product ReFacto® AF.

Participant milestones

Measure	ReFacto (Moroctocog Alfa) B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Overall Study STARTED	288
Overall Study COMPLETED	152
Overall Study NOT COMPLETED	136

Reasons for withdrawal

Measure	ReFacto (Moroctocog Alfa) B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Overall Study Less than expected therapeutic effect	38
Overall Study Lost to Follow-up	27
Overall Study Switch to other Factor VIII preparation	23
Overall Study Intermittent product shortage	21
Overall Study Death	7
Overall Study No reason specified	4
Overall Study Poor cooperation	2
Overall Study Other	14

Baseline Characteristics

Study Evaluating Refacto For Pharmacovigilance

Baseline characteristics by cohort

Measure	ReFacto (Moroctocog Alfa) n=288 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Age, Customized Children < 18 years of age	106 participants n=5 Participants
Age, Customized Adults ≥ 18 years of age	182 participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	288 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Total population for efficacy analysis included all participants with submitted diary cards and severe haemophilia.

Participants with hemophilia A suffer from a hereditary lack of blood clotting factor VIII. As a consequence, the ability of the blood to coagulate is reduced and bleedings at any site or organ of the body may occur after minor injury or even spontaneously. Predominantly, joints, muscles, and internal organs are affected by bleeding complications. Participants reported the occurrence of each bleeding episode while on study. The bleeding rate for each participant was calculated by number of reported episodes per years on study.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=192 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Mean Number of Bleeding Episodes Per Patient Year	13.41 episodes per year Standard Deviation 14.67

PRIMARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Total population for efficacy analysis included all participants with submitted diary cards and severe haemophilia.

Exposure days are the number of days of treatment with ReFacto.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=192 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Mean Number of Bleeding-related Exposure Days Per Patient Year	20.58 days per year Standard Deviation 21.39

PRIMARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Total population for efficacy analysis included all participants with submitted diary cards and severe haemophilia.

Exposure days are the number of days of treatment with ReFacto.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=192 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Mean Number of Exposure Days Per Patient Year	126.76 days per year Standard Deviation 68.81

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Safety population includes all subjects with a baseline visit; (n)=number of participants with events.

AEs are any undesired side effect which occurred in a participant undergoing study treatment independent of whether a correlation with study treatment was suspected or not. SAEs are undesired events which were lethal or life-threatening, made hospitalization or extension of hospital stay necessary, lead to permanent damage with handicap (inability to work), as well as congenital anomalies, malignant disease, or overdosing. Also presence of inhibitors, thrombotic events, erythrocyte agglutination, allergic reactions, less than therapeutic effect, and inhibitor development were considered SAEs.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=288 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Number of Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Non-serious Adverse Events (n=118)	668 events
Number of Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Serious Adverse Events (n=141)	291 events

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Safety population includes all subjects with a baseline visit.

The applied criteria of clinical relevance for de novo inhibitor formation was defined as normal Factor VIII dosage was ineffective to control a bleeding, control of bleeding episodes required increasing Factor VIII dosage, change of concentrate type (administration of activated Prothrombin-Complex Concentrate [aPCC] or recombinant Factor VII [rFVII ]) was needed to stop a bleeding, or change of therapy strategy (intensive prophylaxis or Immune Tolerance Induction [ITI]) was required.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=288 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Number of Participants With de Novo Inhibitor Formation	7 participants

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Total population for efficacy analysis included all participants with submitted diary cards and severe haemophilia.

ReFacto administered as International Units (IU) according to the physician's decision following the drug's summary of product characteristics (SPC) and according to usual care principles.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=192 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Mean Annual ReFacto Consumption Per Patient Year	204509 International units per year Standard Deviation 221723

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Subjective assessment by the physician to evaluate treatment success (i.e., control of bleeding, Factor VIII consumption, treatment efficacy and tolerance, handling of preparation, and days missing from work or school). Physician rated assessment could be categorized as Very satisfied, Satisfied, Unsatisfied, or Very unsatisfied; no criteria was pre-specified for the assessment categories in this observational study.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=169 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Number of Participants for Physicians' Assessment of Satisfaction With Treatment Success Very satisfied	92 participants
Number of Participants for Physicians' Assessment of Satisfaction With Treatment Success Satisfied	73 participants
Number of Participants for Physicians' Assessment of Satisfaction With Treatment Success Unsatisfied	3 participants
Number of Participants for Physicians' Assessment of Satisfaction With Treatment Success Very unsatisfied	1 participants

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Subjective assessment by the physician to evaluate control of bleeding. Physician rated assessment could be categorized as Very good, Good, Moderate, or Poor; no criteria was pre-specified for the assessment categories in this observational study.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=269 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Number of Participants for Physicians' Assessment of Efficacy Very good	111 participants
Number of Participants for Physicians' Assessment of Efficacy Good	111 participants
Number of Participants for Physicians' Assessment of Efficacy Moderate	38 participants
Number of Participants for Physicians' Assessment of Efficacy Poor	9 participants

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Subjective assessment by the participant to evaluate control of bleeding. Patient rated assessment could be categorized as Very good, Good, Moderate, Poor, or No specification; no criteria was pre-specified for the assessment categories in this observational study.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=269 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Number of Participants for Patients' Assessment of Efficacy Very good	103 participants
Number of Participants for Patients' Assessment of Efficacy Good	116 participants
Number of Participants for Patients' Assessment of Efficacy Moderate	35 participants
Number of Participants for Patients' Assessment of Efficacy Poor	11 participants
Number of Participants for Patients' Assessment of Efficacy No specification	4 participants

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Subjective assessment by the physician to evaluate the participants' tolerance of treatment with ReFacto (i.e., dose, administration method, or adverse effects). Physician rated assessment could be categorized as Very good, Good, Moderate, or Poor; no criteria was pre-specified for the assessment categories in this observational study.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=269 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Number of Participants for Physicians' Assessment of Tolerance Very good	130 participants
Number of Participants for Physicians' Assessment of Tolerance Good	137 participants
Number of Participants for Physicians' Assessment of Tolerance Moderate	2 participants

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Subjective assessment by the participant to evaluate tolerance of treatment with ReFacto (i.e., dose, administration method, or adverse effects). Patient rated assessment could be categorized as Very good, Good, Moderate, Poor, or No specification; no criteria was pre-specified for the assessment categories in this observational study.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=269 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Number of Participants for Patients' Assessment of Tolerance Very good	131 participants
Number of Participants for Patients' Assessment of Tolerance Good	132 participants
Number of Participants for Patients' Assessment of Tolerance Moderate	1 participants
Number of Participants for Patients' Assessment of Tolerance Poor	1 participants
Number of Participants for Patients' Assessment of Tolerance No specification	4 participants

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Subjective assessment by the physician to evaluate the participants' handling (preparation and administration) of ReFacto. Physician rated assessment could be categorized as Very good, Good, Moderate, or Poor; no criteria was pre-specified for the assessment categories in this observational study.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=269 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Number of Participants for Physicians' Assessment of Handling of ReFacto Very good	109 participants
Number of Participants for Physicians' Assessment of Handling of ReFacto Good	154 participants
Number of Participants for Physicians' Assessment of Handling of ReFacto Moderate	6 participants

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Subjective assessment by the participant on handling (preparation and administration) of ReFacto. Patient rated assessment could be categorized as Very good, Good, Moderate, Poor, or No specification; no criteria was pre-specified for the assessment categories in this observational study.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=269 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Number of Participants for Patients' Assessment of Handling of ReFacto Very good	99 participants
Number of Participants for Patients' Assessment of Handling of ReFacto Good	154 participants
Number of Participants for Patients' Assessment of Handling of ReFacto Moderate	11 participants
Number of Participants for Patients' Assessment of Handling of ReFacto Poor	1 participants
Number of Participants for Patients' Assessment of Handling of ReFacto No specification	4 participants

SECONDARY outcome

Timeframe: Baseline up to a mean duration of 54 months

Population: Safety population includes all subjects with a baseline visit. N=participants with evaluable data; last measurement available.

Days of sick leave (missing work or school) per month categorized as No days of absence, Number of days of absence, Long-term inability to work or study, Not employed or at school, or No specification.

Outcome measures

Measure	ReFacto (Moroctocog Alfa) n=169 Participants B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Number of Participants for Days of Sick Leave Per Month <6 days of absence	32 participants
Number of Participants for Days of Sick Leave Per Month 6 to 10 days of absence	4 participants
Number of Participants for Days of Sick Leave Per Month >10 days of absence	8 participants
Number of Participants for Days of Sick Leave Per Month Long-term inability to work or study	0 participants
Number of Participants for Days of Sick Leave Per Month Not employed or at school	36 participants
Number of Participants for Days of Sick Leave Per Month No specification	2 participants
Number of Participants for Days of Sick Leave Per Month No days of absence	87 participants

Adverse Events

ReFacto (Moroctocog Alfa)

Serious events: 141 serious events

Other events: 118 other events

Deaths: 0 deaths

Serious adverse events

Measure	ReFacto (Moroctocog Alfa) n=288 participants at risk B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Blood and lymphatic system disorders Haemolysis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Cardiac disorders Acute coronary syndrome	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Cardiac disorders Acute myocardial infarction	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Cardiac disorders Angina pectoris	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Cardiac disorders Cardiomyopathy	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Cardiac disorders Myocardial infarction	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Congenital, familial and genetic disorders Phimosis	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Ear and labyrinth disorders Conductive deafness	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Ear and labyrinth disorders Middle ear effusion	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Acute abdomen	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Dental caries	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Enteritis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Gastric ulcer haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Gastrointestinal haemorrhage	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Gingival bleeding	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Haematemesis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Ileus	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Inguinal hernia	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Intestinal infarction	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Lip haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Melaena	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Mouth haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Oesophageal varices haemorrhage	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Retroperitoneal haematoma	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Small intestinal haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Tooth impacted	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Chills	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Concomitant disease progression	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Condition aggravated	2.1% 6/288 • Baseline up to a mean duration of 54 months 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 Death	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Developmental delay	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Drug ineffective	14.6% 42/288 • Baseline up to a mean duration of 54 months 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 Impaired healing	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Local swelling	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Medical device complication	0.35% 1/288 • Baseline up to a mean duration of 54 months 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	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Thrombosis in device	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Unevaluable event	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Hepatobiliary disorders Cholelithiasis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Hepatobiliary disorders Gallbladder polyp	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Hepatobiliary disorders Hepatic cirrhosis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Hepatobiliary disorders Hepatic failure	1.0% 3/288 • Baseline up to a mean duration of 54 months 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 Acquired immunodeficiency syndrome	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Anogenital warts	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Appendicitis	1.0% 3/288 • Baseline up to a mean duration of 54 months 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 Bronchitis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Bronchopneumonia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Cerebral toxoplasmosis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Device related infection	1.4% 4/288 • Baseline up to a mean duration of 54 months 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 Gastroenteritis	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Implant site infection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Klebsiella sepsis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Meningitis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Osteomyelitis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Paronychia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Pilonidal cyst	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Pneumocystis jiroveci pneumonia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Pneumonia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Pneumonia staphylococcal	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Salmonellosis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Staphylococcal infection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Tooth abscess	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Viral upper respiratory tract infection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Accidental overdose	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Concussion	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Contusion	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Fall	1.7% 5/288 • Baseline up to a mean duration of 54 months 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 Femoral neck fracture	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Femur fracture	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Foot fracture	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Forearm fracture	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Hepatic rupture	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Humerus fracture	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Injury	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Muscle strain	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Post procedural haemorrhage	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Radius fracture	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Skull fractured base	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Subdural haematoma	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Thermal burn	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Traumatic brain injury	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Wound	0.35% 1/288 • Baseline up to a mean duration of 54 months 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	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Anti factor VIII antibody positive	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Anti factor VIII antibody test	7.6% 22/288 • Baseline up to a mean duration of 54 months 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 Antiphospholipid antibodies	0.35% 1/288 • Baseline up to a mean duration of 54 months 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	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Biopsy testes	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Blood urine present	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Catheterisation cardiac	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Coagulation factor VIII level decreased	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Coagulation factor inhibitor assay	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Drug specific antibody present	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Free haemoglobin present	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Gamma-glutamyltransferase increased	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Investigation	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Arthralgia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Arthritis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Fistula	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Flank pain	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Haemarthrosis	2.8% 8/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Haemophilic arthropathy	1.4% 4/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Synovitis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Central nervous system lymphoma	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Cerebral haemorrhage	1.7% 5/288 • Baseline up to a mean duration of 54 months 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 Convulsion	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Cubital tunnel syndrome	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Dyspraxia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Febrile convulsion	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Peripheral sensory neuropathy	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Psychiatric disorders Antisocial behaviour	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Psychiatric disorders Attention deficit/hyperactivity disorder	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Calculus ureteric	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Enuresis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Haematuria	1.4% 4/288 • Baseline up to a mean duration of 54 months 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 Nephrolithiasis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 colic	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Reproductive system and breast disorders Testicular haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Adenoidal hypertrophy	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Asthma	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Henoch-Schonlein purpura	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Adenotonsillectomy	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Arthrodesis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Bone operation	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Central venous catheter removal	1.4% 4/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Dental care	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Ear tube insertion	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Hip arthroplasty	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Joint arthroplasty	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Joint surgery	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Knee arthroplasty	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Ossiculoplasty	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Skin neoplasm excision	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Surgery	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Thyroidectomy	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Tooth extraction	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Vascular operation	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Wisdom teeth removal	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Circulatory collapse	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Haematoma	2.4% 7/288 • Baseline up to a mean duration of 54 months 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 Haemorrhage	3.1% 9/288 • Baseline up to a mean duration of 54 months 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 Vein disorder	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.

Other adverse events

Measure	ReFacto (Moroctocog Alfa) n=288 participants at risk B-domain deleted, recombinant factor VIII (BDDrFVIII) for participants with Hemophilia A in usual health care settings.
Eye disorders Conjunctivitis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Eye disorders Eye haemorrhage	1.0% 3/288 • Baseline up to a mean duration of 54 months 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.
Eye disorders Vision blurred	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Eye disorders Visual impairment	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Abdominal discomfort	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Blood and lymphatic system disorders Iron deficiency anaemia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Blood and lymphatic system disorders Spontaneous haematoma	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Blood and lymphatic system disorders Thrombocytopenia	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Cardiac disorders Palpitations	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Congenital, familial and genetic disorders Phimosis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Ear and labyrinth disorders Tinnitus	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Endocrine disorders Hypothyroidism	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Abdominal distension	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Abdominal pain	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Abdominal pain upper	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Cheilosis	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Dental caries	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Dyspepsia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Gastrointestinal disorder	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Gastrointestinal haemorrhage	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Gastrointestinal pain	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Gingival bleeding	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Haematemesis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Haematochezia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Inflammatory bowel disease	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Lip haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Mouth haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Nausea	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Stomatitis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Tooth loss	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Tooth socket haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Vomiting	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Discomfort	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Drug ineffective	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 General physical health deterioration	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Inflammation	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Influenza like illness	1.0% 3/288 • Baseline up to a mean duration of 54 months 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 Oedema	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Oedema peripheral	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Pain	1.0% 3/288 • Baseline up to a mean duration of 54 months 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	2.1% 6/288 • Baseline up to a mean duration of 54 months 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 Unevaluable event	1.4% 4/288 • Baseline up to a mean duration of 54 months 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.
Hepatobiliary disorders Hepatic cirrhosis	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Drug hypersensitivity	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Seasonal allergy	1.0% 3/288 • Baseline up to a mean duration of 54 months 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 Acquired immunodeficiency syndrome	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Acute tonsillitis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Bronchitis	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Device related infection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Ear infection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Gastrointestinal infection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 HIV infection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Hepatitis C	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Herpes zoster	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Infection	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Influenza	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Localised infection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Nasopharyngitis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Otitis externa	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Otitis media viral	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Parotitis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Pneumonia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Rhinitis	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Sinusitis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Streptococcal infection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Upper respiratory tract infection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Urinary tract infection	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Accident at work	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Bite	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Contusion	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Electric shock	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Excoriation	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Face injury	1.0% 3/288 • Baseline up to a mean duration of 54 months 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 Fall	6.2% 18/288 • Baseline up to a mean duration of 54 months 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 Foot fracture	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Genital injury	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Hand fracture	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Head injury	1.7% 5/288 • Baseline up to a mean duration of 54 months 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 Injury	1.7% 5/288 • Baseline up to a mean duration of 54 months 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 Joint injury	2.1% 6/288 • Baseline up to a mean duration of 54 months 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 Joint sprain	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Limb crushing injury	1.0% 3/288 • Baseline up to a mean duration of 54 months 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 Limb injury	2.8% 8/288 • Baseline up to a mean duration of 54 months 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 Mouth injury	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Muscle rupture	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Open wound	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Post procedural haematoma	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Post procedural haemorrhage	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Skin injury	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Tendon rupture	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Tibia fracture	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Traumatic brain injury	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Traumatic haematoma	1.7% 5/288 • Baseline up to a mean duration of 54 months 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 Traumatic haemorrhage	1.4% 4/288 • Baseline up to a mean duration of 54 months 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 Wound	1.0% 3/288 • Baseline up to a mean duration of 54 months 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 Arthroscopy	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Biopsy stomach	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Blood lactate dehydrogenase increased	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Blood urine present	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Coagulation factor VIII level decreased	3.5% 10/288 • Baseline up to a mean duration of 54 months 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 Endoscopy upper gastrointestinal tract	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Free haemoglobin present	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Liver function test abnormal	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Urine analysis abnormal	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Weight decreased	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Metabolism and nutrition disorders Gout	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Metabolism and nutrition disorders Obesity	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Arthralgia	1.7% 5/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Exostosis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Flank pain	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Haemarthrosis	12.8% 37/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Haemophilic arthropathy	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Joint swelling	1.0% 3/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Lordosis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Muscle haemorrhage	2.8% 8/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Muscle spasms	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Pain in extremity	1.7% 5/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Pain in jaw	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Musculoskeletal and connective tissue disorders Soft tissue haemorrhage	1.0% 3/288 • Baseline up to a mean duration of 54 months 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Melanocytic naevus	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Disturbance in attention	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Dizziness	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Facial nerve disorder	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Headache	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Mental impairment	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Tongue biting	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Psychiatric disorders Affect lability	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Psychiatric disorders Apathy	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Psychiatric disorders Insomnia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Psychiatric disorders Restlessness	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Psychiatric disorders Violence-related symptom	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Haematuria	1.4% 4/288 • Baseline up to a mean duration of 54 months 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 Nephrolithiasis	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 colic	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 haemorrhage	1.0% 3/288 • Baseline up to a mean duration of 54 months 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 pain	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Urinary tract obstruction	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Reproductive system and breast disorders Breast haematoma	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Reproductive system and breast disorders Gynaecomastia	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Reproductive system and breast disorders Testicular pain	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Cough	0.69% 2/288 • Baseline up to a mean duration of 54 months 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 Epistaxis	2.1% 6/288 • Baseline up to a mean duration of 54 months 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 Rhinitis allergic	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Sleep apnoea syndrome	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Tonsillar inflammation	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Dermal cyst	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Ecchymosis	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Haemorrhage subcutaneous	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Rash	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Skin chapped	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Skin lesion	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Skin ulcer	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Subcutaneous nodule	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Skin and subcutaneous tissue disorders Urticaria	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Adenotonsillectomy	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Bursa removal	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Catheterisation venous	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Central venous catheter removal	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Central venous catheterisation	1.4% 4/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Dental care	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Hospitalisation	1.0% 3/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Joint injection	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Medical device implantation	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Medical device removal	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Penile operation	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Plastic surgery	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Radiotherapy to joint	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Suture insertion	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Suture removal	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Synovectomy	0.69% 2/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Tonsillectomy	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Tooth extraction	1.7% 5/288 • Baseline up to a mean duration of 54 months 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.
Surgical and medical procedures Wisdom teeth removal	0.35% 1/288 • Baseline up to a mean duration of 54 months 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 Haematoma	3.1% 9/288 • Baseline up to a mean duration of 54 months 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 Haemorrhage	7.6% 22/288 • Baseline up to a mean duration of 54 months 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 Lymphostasis	0.35% 1/288 • Baseline up to a mean duration of 54 months 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.

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

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