Trial Outcomes & Findings for A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease (NCT NCT01298141)
NCT ID: NCT01298141
Last Updated: 2021-06-08
Results Overview
An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product-related.Treatment-emergent adverse events (TEAEs) were defined as those events which occurred or worsened in severity after first treatment with Replagal AF until 30 days after the last dose. A serious AE (SAE) was any AE occurred at any dose that resulted in death, life-threatening, hospitalization, prolongation of existing hospitalization, persistent or significant disability or incapacity and congenital anomaly or birth defect.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
171 participants
Primary outcome timeframe
From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
Results posted on
2021-06-08
Participant Flow
This multicenter study was conducted at 12 sites in Canada between 10 Aug 2011 (first participant first visit) and 25 Sep 2017 (last participant last visit).
A total of 171 participants enrolled into cohort 1 (participants from Canadian Fabry Disease Initiative \[CFDI\]) and cohort 2 (participants who participated in study REP001a) and among them 167 participants received at least one full or partial dose of Replagal (agalsidase alfa) animal free (AF).
Participant milestones
| Measure |
Replagal (Agalsidase Alfa)
Participants in cohort 1 received Replagal AF intravenous (IV) infusion at a dose of 0.2 milligram per kilogram (mg/kg) body weight every other week (EOW) and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Overall Study
STARTED
|
171
|
|
Overall Study
Treated
|
167
|
|
Overall Study
COMPLETED
|
140
|
|
Overall Study
NOT COMPLETED
|
31
|
Reasons for withdrawal
| Measure |
Replagal (Agalsidase Alfa)
Participants in cohort 1 received Replagal AF intravenous (IV) infusion at a dose of 0.2 milligram per kilogram (mg/kg) body weight every other week (EOW) and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Refusal of Required Study Procedures
|
1
|
|
Overall Study
Withdrawal by Subject
|
6
|
|
Overall Study
Termination of Study by the Investigator
|
5
|
|
Overall Study
Other
|
5
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Death
|
6
|
|
Overall Study
Not treated
|
4
|
Baseline Characteristics
A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease
Baseline characteristics by cohort
| Measure |
Replagal (Agalsidase Alfa)
n=167 Participants
Participants in cohort 1 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight EOW and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Age, Continuous
|
48.85 Years
STANDARD_DEVIATION 14.821 • n=5 Participants
|
|
Sex: Female, Male
Female
|
76 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
91 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
165 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
160 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)Population: Safety Population included all participants who received at least one full or partial infusion of Replagal AF.
An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product-related.Treatment-emergent adverse events (TEAEs) were defined as those events which occurred or worsened in severity after first treatment with Replagal AF until 30 days after the last dose. A serious AE (SAE) was any AE occurred at any dose that resulted in death, life-threatening, hospitalization, prolongation of existing hospitalization, persistent or significant disability or incapacity and congenital anomaly or birth defect.
Outcome measures
| Measure |
Replagal (Agalsidase Alfa)
n=167 Participants
Participants in cohort 1 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight EOW and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Any TEAE
|
163 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Any Serious TEAE
|
74 Participants
|
|
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Any TEAE Leading to Treatment Discontinuation
|
7 Participants
|
PRIMARY outcome
Timeframe: From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)Population: Safety Population included all participants who received at least one full or partial infusion of Replagal AF.
An IRR (also referred to as infusion-related adverse event \[IRAE\]) was defined as an AE that began either during the infusion or within 12 hours after the start of the infusion and was judged as possibly or probably related to study drug. The IRRs were classified based on the severity as Mild=No limitation of usual activities, Moderate=Some limitation of usual activities, Severe=Inability to carry out usual activities and Life-threatening=Immediate risk of death. The number of participants with infusion-related reactions was reported.
Outcome measures
| Measure |
Replagal (Agalsidase Alfa)
n=167 Participants
Participants in cohort 1 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight EOW and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Number of Participants With Infusion-Related Reactions (IRR)
Mild
|
21 Participants
|
|
Number of Participants With Infusion-Related Reactions (IRR)
Moderate
|
16 Participants
|
|
Number of Participants With Infusion-Related Reactions (IRR)
Severe
|
3 Participants
|
|
Number of Participants With Infusion-Related Reactions (IRR)
Life-threatening
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline (within 6 months prior to first dose) up to Week 129Population: Safety population included all participants who received at least one full or partial infusion of Replagal AF.
The IgA status was measured using enzyme-linked immunosorbent assay (ELISA). Number of participants who reported positive to IgA was reported.
Outcome measures
| Measure |
Replagal (Agalsidase Alfa)
n=167 Participants
Participants in cohort 1 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight EOW and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Number of Participants Who Reported Positive to Immunoglobulin A (IgA)
|
10 Participants
|
PRIMARY outcome
Timeframe: Baseline (within 6 months prior to first dose) up to Week 129Population: Safety population included all participants who received at least one full or partial infusion of Replagal AF.
The IgE status was measured using ELISA. Number of participants who reported positive to IgE was reported.
Outcome measures
| Measure |
Replagal (Agalsidase Alfa)
n=167 Participants
Participants in cohort 1 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight EOW and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Number of Participants Who Reported Positive to Immunoglobulin E (IgE)
|
1 Participants
|
PRIMARY outcome
Timeframe: Baseline (within 6 months prior to first dose) up to Week 129Population: Safety population included all participants who received at least one full or partial infusion of Replagal AF.
The IgM status was measured using ELISA. Number of participants who reported positive to IgM was reported.
Outcome measures
| Measure |
Replagal (Agalsidase Alfa)
n=167 Participants
Participants in cohort 1 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight EOW and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Number of Participants Who Reported Positive to Immunoglobulin M (IgM)
|
48 Participants
|
PRIMARY outcome
Timeframe: Baseline (within 6 months prior to first dose) up to Week 285Population: Safety population included all participants who received at least one full or partial infusion of Replagal AF.
The ADA status was measured using ELISA and electrochemiluminescent (ECL) immunoassay. Number of participants who reported positive to ADA was reported.
Outcome measures
| Measure |
Replagal (Agalsidase Alfa)
n=167 Participants
Participants in cohort 1 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight EOW and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Number of Participants Who Reported Positive to Anti-drug Antibody (ADA)
|
42 Participants
|
PRIMARY outcome
Timeframe: Baseline (within 6 months prior to first dose) up to Week 285Population: Safety population included all participants who received at least one full or partial infusion of Replagal AF.
The NAb status was measured using enzyme activity inhibition assay. Number of participants who reported positive to NAb was reported.
Outcome measures
| Measure |
Replagal (Agalsidase Alfa)
n=167 Participants
Participants in cohort 1 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight EOW and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Number of Participants Who Reported Positive to Neutralizing Antibody (NAb)
|
27 Participants
|
Adverse Events
Replagal (Agalsidase Alfa)
Serious events: 74 serious events
Other events: 160 other events
Deaths: 6 deaths
Serious adverse events
| Measure |
Replagal (Agalsidase Alfa)
n=167 participants at risk
Participants in cohort 1 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight EOW and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
3.0%
5/167 • Number of events 5 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Blood and lymphatic system disorders
Pancytopenia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Osteolysis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Osteonecrosis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Splenic neoplasm malignancy unspecified
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Vascular disorders
Deep vein thrombosis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Vascular disorders
Thrombophlebitis superficial
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Ear and labyrinth disorders
Hypoacusis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Ear and labyrinth disorders
Sudden hearing loss
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Ear and labyrinth disorders
Vertigo positional
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Ear and labyrinth disorders
Vestibular disorder
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Eye disorders
Eye swelling
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.60%
1/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Abdominal pain
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Colitis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Constipation
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Dysphagia
|
1.8%
3/167 • Number of events 3 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Gastric haemorrhage
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
1.2%
2/167 • Number of events 3 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Hypoaesthesia oral
|
0.60%
1/167 • Number of events 4 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Intestinal perforation
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Nausea
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Pancreatitis
|
1.2%
2/167 • Number of events 3 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Paraesthesia oral
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Retroperitoneal haematoma
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Swollen tongue
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Umbilical hernia
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Asthenia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Chest pain
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Device malfunction
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Malaise
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Non-Cardiac chest pain
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Oedema peripheral
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Pyrexia
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Congenital, familial and genetic disorders
Fabry's disease
|
1.8%
3/167 • Number of events 3 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Congenital, familial and genetic disorders
Pyloric stenosis
|
0.60%
1/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Acute coronary syndrome
|
2.4%
4/167 • Number of events 4 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Acute myocardial infarction
|
1.8%
3/167 • Number of events 3 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Angina pectoris
|
3.6%
6/167 • Number of events 6 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Angina unstable
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Aortic valve incompetence
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Aortic valve stenosis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Atrial fibrillation
|
3.0%
5/167 • Number of events 7 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Atrial flutter
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Cardiac arrest
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Cardiac failure
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Cardiac failure congestive
|
2.4%
4/167 • Number of events 4 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Coronary artery disease
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Coronary artery stenosis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Hypertrophic cardiomyopathy
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Intracardiac thrombus
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Left ventricular dysfunction
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Myocardial infarction
|
4.2%
7/167 • Number of events 8 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Palpitations
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Supraventricular tachycardia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Ventricular tachycardia
|
4.2%
7/167 • Number of events 7 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Immune system disorders
Anaphylactic reaction
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Immune system disorders
Kidney transplant rejection
|
0.60%
1/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Bacteraemia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Bacterial sepsis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Beta haemolytic streptococcal infection
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Cellulitis
|
4.2%
7/167 • Number of events 9 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Cholangitis suppurative
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Cytomegalovirus viraemia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Device related infection
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Escherichia bacteraemia
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Infection
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Influenza
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Perihepatic abscess
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Pneumonia
|
4.2%
7/167 • Number of events 7 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Pneumonia adenoviral
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Pneumonia cytomegaloviral
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Pneumonia primary atypical
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Pseudomonal sepsis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Sepsis
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Septic shock
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Tooth abscess
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Upper respiratory tract infection
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Urosepsis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Accident
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
0.60%
1/167 • Number of events 4 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Fall
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Psychosis postoperative
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Scapula fracture
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Soft tissue injury
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Investigations
Ejection fraction decreased
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Investigations
Electrocardiogram qt prolonged
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Investigations
Enterococcus test positive
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Investigations
Heart rate decreased
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Investigations
Troponin increased
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Investigations
Weight decreased
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Renal and urinary disorders
Nephropathy
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Renal and urinary disorders
Renal failure
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Renal and urinary disorders
Renal failure acute
|
4.2%
7/167 • Number of events 8 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Renal and urinary disorders
Renal failure chronic
|
4.8%
8/167 • Number of events 9 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Hepatobiliary disorders
Biloma
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Hepatobiliary disorders
Cholangitis acute
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Hepatobiliary disorders
Cholecystitis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Hepatobiliary disorders
Cholelithiasis
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Metabolism and nutrition disorders
Dehydration
|
1.8%
3/167 • Number of events 3 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Aphasia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Cerebral infarction
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Cerebrovascular accident
|
4.8%
8/167 • Number of events 8 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Hypoaesthesia
|
0.60%
1/167 • Number of events 5 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Ischaemic stroke
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Nervous system disorder
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Neuralgia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Presyncope
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Syncope
|
1.8%
3/167 • Number of events 3 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Tension headache
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Transient ischaemic attack
|
1.8%
3/167 • Number of events 4 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Tremor
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Surgical and medical procedures
Aortic valve replacement
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Surgical and medical procedures
Cardiac ablation
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Surgical and medical procedures
Cardiac pacemaker insertion
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Surgical and medical procedures
Cardiac pacemaker replacement
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Surgical and medical procedures
Cardiac pacemaker revision
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Surgical and medical procedures
Implantable defibrillator insertion
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Surgical and medical procedures
Implantable defibrillator replacement
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Surgical and medical procedures
Mitral valve replacement
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Psychiatric disorders
Depression
|
1.2%
2/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Reproductive system and breast disorders
Endometrial hyperplasia
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Reproductive system and breast disorders
Priapism
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Choking sensation
|
0.60%
1/167 • Number of events 3 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.60%
1/167 • Number of events 3 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
1.2%
2/167 • Number of events 5 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Increased upper airway secretion
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
0.60%
1/167 • Number of events 2 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Tracheal stenosis
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Skin and subcutaneous tissue disorders
Hypoaesthesia facial
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Skin and subcutaneous tissue disorders
Piloerection
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Skin and subcutaneous tissue disorders
Pruritus generalised
|
0.60%
1/167 • Number of events 1 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
Other adverse events
| Measure |
Replagal (Agalsidase Alfa)
n=167 participants at risk
Participants in cohort 1 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight EOW and cohort 2 received Replagal AF IV infusion at a dose of 0.2 mg/kg body weight weekly until the drug became commercially available or the participant discontinued, whichever came first.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.6%
11/167 • Number of events 25 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
26.9%
45/167 • Number of events 68 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
27.5%
46/167 • Number of events 63 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
8.4%
14/167 • Number of events 17 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
13.2%
22/167 • Number of events 30 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
6.0%
10/167 • Number of events 12 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
13.8%
23/167 • Number of events 29 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
12.6%
21/167 • Number of events 22 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
8.4%
14/167 • Number of events 14 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
7.2%
12/167 • Number of events 12 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
20.4%
34/167 • Number of events 49 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Vascular disorders
Flushing
|
5.4%
9/167 • Number of events 49 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Vascular disorders
Hypertension
|
10.2%
17/167 • Number of events 22 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Vascular disorders
Hypotension
|
10.2%
17/167 • Number of events 23 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Ear and labyrinth disorders
Ear pain
|
6.6%
11/167 • Number of events 11 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Ear and labyrinth disorders
Tinnitus
|
10.2%
17/167 • Number of events 17 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Ear and labyrinth disorders
Vertigo
|
13.8%
23/167 • Number of events 26 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Eye disorders
Vision blurred
|
9.6%
16/167 • Number of events 19 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Abdominal discomfort
|
7.8%
13/167 • Number of events 14 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Abdominal pain
|
17.4%
29/167 • Number of events 50 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.2%
17/167 • Number of events 21 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Constipation
|
8.4%
14/167 • Number of events 16 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Diarrhoea
|
30.5%
51/167 • Number of events 90 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Dyspepsia
|
6.6%
11/167 • Number of events 12 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
6.6%
11/167 • Number of events 12 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Haematochezia
|
5.4%
9/167 • Number of events 9 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Nausea
|
34.1%
57/167 • Number of events 119 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Gastrointestinal disorders
Vomiting
|
26.3%
44/167 • Number of events 79 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Asthenia
|
8.4%
14/167 • Number of events 18 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Chest discomfort
|
6.6%
11/167 • Number of events 16 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Chest pain
|
9.6%
16/167 • Number of events 22 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Chills
|
9.0%
15/167 • Number of events 30 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Fatigue
|
41.9%
70/167 • Number of events 95 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Influenza like illness
|
8.4%
14/167 • Number of events 21 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Non-Cardiac chest pain
|
13.8%
23/167 • Number of events 27 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Oedema
|
5.4%
9/167 • Number of events 10 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Oedema peripheral
|
33.5%
56/167 • Number of events 82 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Pain
|
9.6%
16/167 • Number of events 21 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
General disorders
Pyrexia
|
16.8%
28/167 • Number of events 35 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Angina pectoris
|
13.2%
22/167 • Number of events 44 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Cardiac disorders
Palpitations
|
21.0%
35/167 • Number of events 49 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Bronchitis
|
10.8%
18/167 • Number of events 21 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Cellulitis
|
6.6%
11/167 • Number of events 15 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Cystitis
|
6.6%
11/167 • Number of events 15 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Ear infection
|
7.8%
13/167 • Number of events 14 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Influenza
|
18.6%
31/167 • Number of events 45 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Localised infection
|
7.2%
12/167 • Number of events 17 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Lower respiratory tract infection
|
11.4%
19/167 • Number of events 21 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Nasopharyngitis
|
38.3%
64/167 • Number of events 123 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Pneumonia
|
6.6%
11/167 • Number of events 18 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Sinusitis
|
10.2%
17/167 • Number of events 25 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Upper respiratory tract infection
|
8.4%
14/167 • Number of events 20 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Infections and infestations
Urinary tract infection
|
13.8%
23/167 • Number of events 38 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Contusion
|
12.6%
21/167 • Number of events 29 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Injury, poisoning and procedural complications
Skin laceration
|
5.4%
9/167 • Number of events 10 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Investigations
Cardiac murmur
|
7.2%
12/167 • Number of events 16 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Investigations
Temperature difference of extremities
|
9.6%
16/167 • Number of events 18 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Metabolism and nutrition disorders
Gout
|
5.4%
9/167 • Number of events 16 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Balance disorder
|
5.4%
9/167 • Number of events 9 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Dizziness
|
32.3%
54/167 • Number of events 85 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Headache
|
32.3%
54/167 • Number of events 104 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Hypoaesthesia
|
15.6%
26/167 • Number of events 31 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Migraine
|
7.8%
13/167 • Number of events 16 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Neuralgia
|
19.2%
32/167 • Number of events 63 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Paraesthesia
|
17.4%
29/167 • Number of events 31 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Syncope
|
6.0%
10/167 • Number of events 11 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Nervous system disorders
Tremor
|
10.2%
17/167 • Number of events 19 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Psychiatric disorders
Anxiety
|
11.4%
19/167 • Number of events 22 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Psychiatric disorders
Depression
|
7.2%
12/167 • Number of events 13 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Psychiatric disorders
Insomnia
|
7.8%
13/167 • Number of events 16 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
30.5%
51/167 • Number of events 82 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
24.0%
40/167 • Number of events 58 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
8.4%
14/167 • Number of events 16 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
9.6%
16/167 • Number of events 25 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
9.6%
16/167 • Number of events 19 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
14.4%
24/167 • Number of events 34 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
6.6%
11/167 • Number of events 17 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory tract congestion
|
6.0%
10/167 • Number of events 11 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Skin and subcutaneous tissue disorders
Angiokeratoma
|
6.6%
11/167 • Number of events 11 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
11.4%
19/167 • Number of events 29 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.0%
10/167 • Number of events 13 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.8%
18/167 • Number of events 24 • From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER