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Safety and Efficacy Study of Several Replagal Dosing Regimens on Cardiac Function in Adults With Fabry Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00864851
Recruitment Status : Completed
First Posted : March 19, 2009
Results First Posted : June 6, 2014
Last Update Posted : December 14, 2018
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Fabry Disease
Intervention Biological: Replagal
Enrollment 44
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly
Hide Arm/Group Description Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks. Patients randomized to receive Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks. Patients randomized to receive Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
Period Title: Overall Study
Started 20 19 5
Completed 17 18 5
Not Completed 3 1 0
Reason Not Completed
Withdrawal by Subject             0             1             0
Physician Decision             1             0             0
Death             1             0             0
Patient uncooperative             1             0             0
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly Total
Hide Arm/Group Description Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks. Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks. Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks. Total of all reporting groups
Overall Number of Baseline Participants 20 19 5 44
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 19 participants 5 participants 44 participants
50.3  (7.23) 51.8  (11.42) 49.4  (9.75) 50.8  (9.34)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 5 participants 44 participants
18 to <45 years 5 6 1 12
>=45 years 15 13 4 32
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 5 participants 44 participants
Female
6
  30.0%
9
  47.4%
3
  60.0%
18
  40.9%
Male
14
  70.0%
10
  52.6%
2
  40.0%
26
  59.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 5 participants 44 participants
Hispanic or Latino
1
   5.0%
1
   5.3%
0
   0.0%
2
   4.5%
Not Hispanic or Latino
19
  95.0%
18
  94.7%
5
 100.0%
42
  95.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 5 participants 44 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
20
 100.0%
19
 100.0%
5
 100.0%
44
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Baseline Left Ventricular Mass Indexed to Height (LVMI)  
Mean (Standard Deviation)
Unit of measure:  G/m^2.7
Number Analyzed 20 participants 19 participants 5 participants 44 participants
76.1  (22.8) 82.6  (28.3) 99.3  (46.2) 81.5  (28.5)
Baseline Maximal Oxygen Consumption (VO2 max) at Peak Exercise   [1] 
Mean (Standard Deviation)
Unit of measure:  mL/min/kg
Number Analyzed 20 participants 19 participants 5 participants 44 participants
20.2  (6.20) 22.6  (6.89) 24.0  (11.69) 21.6  (7.05)
[1]
Measure Description: 0.2 mg/kg Every Other Week: n=19 0.2 mg/kg Weekly: n=16 0.4 mg/kg Weekly: n=4 Total: n=39
Baseline Distance Walked in 6-Minute Walk Test (6MWT)   [1] 
Mean (Standard Deviation)
Unit of measure:  m
Number Analyzed 20 participants 19 participants 5 participants 44 participants
459.6  (103.0) 514.3  (87.3) 530.7  (90.2) 492.8  (97.0)
[1]
Measure Description: 0.2 mg/kg Every Other Week: n=18 0.2 mg/kg Weekly: n=19 0.4 mg/kg Weekly: n=5 Total: n=42
Baseline Minnesota Living with Heart Failure Questionnaire (MLHF-Q) Summary Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 20 participants 19 participants 5 participants 44 participants
37.0  (23.8) 21.1  (21.0) 19.6  (26.5) 28.1  (23.8)
[1]
Measure Description: Quality of life (QoL) was evaluated using the MLHF-Q, version 2. The questionnaire is designed to assess the degree to which heart failure symptoms affect a patient's daily life. The summary score ranges from 0 to 105, with a score of 105 representing the highest adverse impact on a patient's QoL.
Baseline New York Heart Association (NYHA) Functional Class   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants 19 participants 5 participants 44 participants
Class I 6 10 2 18
Class II 11 9 2 22
Class III 3 0 1 4
Class IV 0 0 0 0
[1]
Measure Description:

Class I: Cardiac disease without limitation of physical activity. Ordinary physical activity does not cause undue symptoms.

Class II: Cardiac disease with slight limitation of physical activity. Comfortable at rest, but ordinary physical activity causes symptoms.

Class III: Cardiac disease with marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes symptoms.

Class IV: Cardiac disease and unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest.

Note: Symptoms include fatigue, palpitation or dyspnea

Baseline Plasma Globotriaosylceramide (GB3)  
Mean (Standard Deviation)
Unit of measure:  Nmol/ml
Number Analyzed 20 participants 19 participants 5 participants 44 participants
6.067  (3.388) 5.652  (5.212) 5.292  (1.865) 5.800  (4.104)
Baseline Estimated Glomerular Filtration Rate (eGFR)  
Mean (Standard Deviation)
Unit of measure:  mL/min/1.73 m^2
Number Analyzed 20 participants 19 participants 5 participants 44 participants
82.0  (34.1) 78.1  (33.8) 72.1  (31.2) 79.2  (33.1)
Baseline Urinary Albumin/Creatinine (A/Cr) Ratio  
Mean (Standard Deviation)
Unit of measure:  Mg/g
Number Analyzed 20 participants 19 participants 5 participants 44 participants
313.4  (614.07) 293.4  (521.23) 298.2  (175.85) 303.0  (532.27)
1.Primary Outcome
Title Change From Baseline to Month 12 in Left Ventricular Mass Indexed to Height (LVMI)
Hide Description Left ventricular mass (LVM) was measured through echocardiography.
Time Frame Baseline, Month 12 (Week 53)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly
Hide Arm/Group Description:
Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
Overall Number of Participants Analyzed 15 18 5
Mean (Standard Deviation)
Unit of Measure: g/m^2.7
3.2  (12.5) 0.5  (15.8) -10.3  (11.8)
2.Secondary Outcome
Title Change From Baseline to Month 12 in Maximal Oxygen Consumption (VO2 Max) at Peak Exercise
Hide Description Exercise tolerance as measured by VO2 max at peak exercise using the standard exponential exercise protocol (STEEP).
Time Frame Baseline, Month 12 (Week 53)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly
Hide Arm/Group Description:
Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
Overall Number of Participants Analyzed 14 15 4
Mean (Standard Deviation)
Unit of Measure: mL/min/kg
-2.0  (3.24) -0.3  (4.76) 2.2  (5.85)
3.Secondary Outcome
Title Change From Baseline to Month 12 in Distance Walked in 6-Minute Walk Test (6MWT)
Hide Description Exercise tolerance using the 6MWT was measured as the total distance walked in 6 minutes.
Time Frame Baseline, Month 12 (Week 53)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly
Hide Arm/Group Description:
Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
Overall Number of Participants Analyzed 15 18 5
Mean (Standard Deviation)
Unit of Measure: m
-10.4  (87.7) 37.9  (70.5) 24.7  (45.7)
4.Secondary Outcome
Title Change From Baseline to Month 12 in the Minnesota Living With Heart Failure Questionnaire (MLHF-Q) Summary Score
Hide Description Quality of life (QoL) was evaluated using the MLHF-Q, version 2. The questionnaire is designed to assess the degree to which heart failure symptoms affect a patient's daily life. The summary score ranges from 0 to 105, with a score of 105 representing the highest adverse impact on a patient's QoL.
Time Frame Baseline, Month 12 (Week 53)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly
Hide Arm/Group Description:
Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
Overall Number of Participants Analyzed 17 17 5
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-3.1  (16.7) 2.1  (11.5) -8.6  (12.3)
5.Secondary Outcome
Title Change From Baseline to Month 12 in New York Heart Association (NYHA) Functional Class
Hide Description

The NYHA functional classification system relates symptoms to everyday activities and the patient's quality of life.

NYHA Classification - The Stages of Heart Failure:

Class I (Mild): No limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, or dyspnea (shortness of breath).

Class II (Mild): Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, or dyspnea.

Class III (Moderate): Marked limitation of physical activity. Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea.

Class IV (Severe): Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency at rest. If any physical activity is undertaken, discomfort is increased.

Time Frame Baseline, Month 12 (Week 53)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly
Hide Arm/Group Description:
Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
Overall Number of Participants Analyzed 17 18 5
Measure Type: Number
Unit of Measure: participants
Improved ≥ 1 NYHA Functional Class 2 2 2
Maintained NYHA Functional Class 15 16 3
6.Secondary Outcome
Title Change From Baseline to Month 12 in Plasma Globotriaosylceramide (GB3)
Hide Description [Not Specified]
Time Frame Baseline, Month 12 (Week 53)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly
Hide Arm/Group Description:
Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
Overall Number of Participants Analyzed 17 18 5
Mean (Standard Deviation)
Unit of Measure: nmol/ml
-1.046  (2.256) -2.132  (4.363) -2.076  (1.248)
7.Secondary Outcome
Title Change From Baseline to Month 12 in Estimated Glomerular Filtration Rate (eGFR)
Hide Description Renal function was assessed by an evaluation of change from baseline to Month 12 in eGFR as calculated using the Modification of Diet for Renal Disease (MDRD) equation.
Time Frame Baseline, Month 12 (Week 53)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly
Hide Arm/Group Description:
Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
Overall Number of Participants Analyzed 17 18 5
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
-1.2  (12.2) -3.3  (12.7) -1.7  (9.9)
8.Secondary Outcome
Title Change From Baseline to Month 12 in Urinary Albumin/Creatinine (A/Cr) Ratio
Hide Description [Not Specified]
Time Frame Baseline, Month 12 (Week 53)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal.
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly
Hide Arm/Group Description:
Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
Overall Number of Participants Analyzed 17 17 5
Mean (Standard Deviation)
Unit of Measure: mg/g
83.9  (624.82) -54.1  (322.51) -54.2  (294.86)
9.Secondary Outcome
Title Safety Evaluation
Hide Description Adverse events were collected throughout the study, from the time of informed consent to approximately 30 days post-final infusion.
Time Frame 56 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat (ITT) Population: All randomized patients who received at least 1 complete or partial dose of Replagal. Analyses were performed on the ITT population because it was identical to the safety population.
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly Overall
Hide Arm/Group Description:
Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks.
Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks.
Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks.
Total of all reporting groups.
Overall Number of Participants Analyzed 20 19 5 44
Measure Type: Number
Unit of Measure: participants
No adverse event (AE) 1 2 0 3
At least one AE 19 17 5 41
At least one study drug-related AE 6 6 2 14
At least one infusion-related AE 5 4 2 11
At least one severe or life-threatening AE 8 4 0 12
At least one serious AE (SAE) 8 5 2 15
At least one study drug-related SAE 1 0 0 1
Discontinued due to an AE 0 0 0 0
Deaths 1 0 0 1
Time Frame 56 Weeks
Adverse Event Reporting Description Adverse events were collected throughout the study, from the time of informed consent to approximately 30 days post-final infusion.
 
Arm/Group Title Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly Overall
Hide Arm/Group Description Patients who received Replagal 0.2 mg/kg via intravenous infusion every other week for 52 weeks. Patients who received Replagal 0.2 mg/kg via intravenous infusion every week for 52 weeks. Patients who received Replagal 0.4 mg/kg via intravenous infusion every week for 52 weeks. Total of all reporting groups.
All-Cause Mortality
Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly Overall
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly Overall
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   8/20 (40.00%)      5/19 (26.32%)      2/5 (40.00%)      15/44 (34.09%)    
Cardiac disorders         
Palpitations  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Sinus bradycardia  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  1 1/44 (2.27%)  1
Angina pectoris  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Atrial fibrillation  1  1/20 (5.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  2
Atrioventricular block complete  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Cardiac arrest  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Coronary artery stenosis  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Supraventricular tachycardia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Gastrointestinal disorders         
Nausea  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Vomiting  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
General disorders         
Inflammation  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Infections and infestations         
Meningitis aseptic  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Injury, poisoning and procedural complications         
Traumatic haematoma  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Musculoskeletal and connective tissue disorders         
Musculoskeletal chest pain  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Gouty arthritis  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Nervous system disorders         
Facial paresis  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  1 1/44 (2.27%)  1
Spastic paralysis  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Psychiatric disorders         
Depression  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Renal and urinary disorders         
Renal failure chronic  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Vascular disorders         
Hypotension  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Replagal 0.2 mg/kg, IV, Every Other Week Replagal 0.2 mg/kg, IV, Weekly Replagal 0.4 mg/kg, IV, Weekly Overall
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/20 (95.00%)      17/19 (89.47%)      5/5 (100.00%)      41/44 (93.18%)    
Blood and lymphatic system disorders         
Anaemia  1  0/20 (0.00%)  0 2/19 (10.53%)  2 0/5 (0.00%)  0 2/44 (4.55%)  2
Neutropenia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Cardiac disorders         
Palpitations  1  2/20 (10.00%)  2 1/19 (5.26%)  1 1/5 (20.00%)  1 4/44 (9.09%)  4
Bundle branch block right  1  0/20 (0.00%)  0 2/19 (10.53%)  2 1/5 (20.00%)  1 3/44 (6.82%)  3
Tachycardia  1  0/20 (0.00%)  0 2/19 (10.53%)  2 1/5 (20.00%)  1 3/44 (6.82%)  3
Extrasystoles  1  0/20 (0.00%)  0 1/19 (5.26%)  2 1/5 (20.00%)  2 2/44 (4.55%)  4
Sinus bradycardia  1  0/20 (0.00%)  0 1/19 (5.26%)  1 1/5 (20.00%)  1 2/44 (4.55%)  2
Ventricular tachycardia  1  1/20 (5.00%)  4 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  5
Angina pectoris  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Atrial fibrillation  1  1/20 (5.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  2
Atrioventricular block complete  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Atrioventricular block first degree  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Bradycardia  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Cardiac arrest  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Cardiac failure  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Coronary artery stenosis  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Dilatation atrial  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Hypertrophic cardiomyopathy  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Left ventricular hypertrophy  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Sinus tachycardia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Supraventricular extrasystoles  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Supraventricular tachycardia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Congenital, familial and genetic disorders         
Myocardial bridging  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Ear and labyrinth disorders         
Ear pain  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Hypoacusis  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Tinnitus  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Vertigo  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Eye disorders         
Vision blurred  1  1/20 (5.00%)  1 0/19 (0.00%)  0 1/5 (20.00%)  1 2/44 (4.55%)  2
Blindness  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Eye pain  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  1 1/44 (2.27%)  1
Photophobia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Gastrointestinal disorders         
Pyrexia  1  3/20 (15.00%)  4 2/19 (10.53%)  2 1/5 (20.00%)  1 6/44 (13.64%)  7
Nausea  1  2/20 (10.00%)  4 3/19 (15.79%)  9 0/5 (0.00%)  0 5/44 (11.36%)  13
Dental caries  1  3/20 (15.00%)  3 1/19 (5.26%)  1 0/5 (0.00%)  0 4/44 (9.09%)  4
Diarrhoea  1  2/20 (10.00%)  2 2/19 (10.53%)  3 0/5 (0.00%)  0 4/44 (9.09%)  5
Vomiting  1  1/20 (5.00%)  1 2/19 (10.53%)  2 0/5 (0.00%)  0 3/44 (6.82%)  3
Toothache  1  2/20 (10.00%)  3 0/19 (0.00%)  0 0/5 (0.00%)  0 2/44 (4.55%)  3
Abdominal pain  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Constipation  1  0/20 (0.00%)  0 1/19 (5.26%)  2 0/5 (0.00%)  0 1/44 (2.27%)  2
Dyspepsia  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Dysphagia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Flatulence  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Gastrointestinal disorder  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Haemorrhoids  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Hiatus hernia  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Hypoaesthesia oral  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Inguinal hernia  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Tooth impacted  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
General disorders         
Fatigue  1  5/20 (25.00%)  13 7/19 (36.84%)  13 1/5 (20.00%)  13 13/44 (29.55%)  39
Oedema peripheral  1  1/20 (5.00%)  1 4/19 (21.05%)  5 1/5 (20.00%)  3 6/44 (13.64%)  9
Chest pain  1  2/20 (10.00%)  2 2/19 (10.53%)  2 1/5 (20.00%)  1 5/44 (11.36%)  5
Non-cardiac chest pain  1  1/20 (5.00%)  1 2/19 (10.53%)  3 0/5 (0.00%)  0 3/44 (6.82%)  4
Chest discomfort  1  1/20 (5.00%)  1 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  2
Chills  1  2/20 (10.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 2/44 (4.55%)  2
Catheter site haematoma  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Catheter site swelling  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Feeling cold  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Feeling hot  1  1/20 (5.00%)  3 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  3
Implant site paraesthesia  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Implant site reaction  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Inflammation  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Influenza like illness  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Infusion site haematoma  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Malaise  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Pain  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Thirst  1  1/20 (5.00%)  8 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  8
Hepatobiliary disorders         
Biliary dilataton  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Liver injury  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Infections and infestations         
Nasopharyngitis  1  2/20 (10.00%)  2 6/19 (31.58%)  11 0/5 (0.00%)  0 8/44 (18.18%)  13
Bronchitis  1  2/20 (10.00%)  2 3/19 (15.79%)  3 1/5 (20.00%)  1 6/44 (13.64%)  6
Respiratory tract infection  1  0/20 (0.00%)  0 4/19 (21.05%)  4 0/5 (0.00%)  0 4/44 (9.09%)  4
Upper respiratory tract infection  1  1/20 (5.00%)  1 3/19 (15.79%)  3 0/5 (0.00%)  0 4/44 (9.09%)  4
Viral infection  1  1/20 (5.00%)  1 2/19 (10.53%)  2 0/5 (0.00%)  0 3/44 (6.82%)  3
Sinusitis  1  1/20 (5.00%)  1 0/19 (0.00%)  0 1/5 (20.00%)  1 2/44 (4.55%)  2
Urinary tract infection  1  1/20 (5.00%)  1 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  2
Ear infection  1  1/20 (5.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  2
Gastroenteritis  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Influenza  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Localised infection  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Lower respiratory tract infection  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Meningitis aseptic  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Oral herpes  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Pharyngitis  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Post procedural infection  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  1 1/44 (2.27%)  1
Rhinitis  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Skin infection  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  1 1/44 (2.27%)  1
Urinary tract infection bacterial  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Vaginal infection  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Injury, poisoning and procedural complications         
Contusion  1  1/20 (5.00%)  1 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  2
Procedural pain  1  1/20 (5.00%)  1 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  2
Fall  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Mouth injury  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Muscle injury  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Rib fracture  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Skin laceration  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Tendon rupture  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Tooth injury  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Traumatic haematoma  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Investigations         
Cardiac murmur  1  2/20 (10.00%)  2 2/19 (10.53%)  2 0/5 (0.00%)  0 4/44 (9.09%)  4
Aspartate aminotransferase increased  1  2/20 (10.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 2/44 (4.55%)  2
Blood lactate dehydrogenase increased  1  2/20 (10.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 2/44 (4.55%)  2
Gamma-glutamyltransferase increased  1  2/20 (10.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 2/44 (4.55%)  2
Haematocrit decreased  1  1/20 (5.00%)  1 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  2
Red blood cell count decreased  1  1/20 (5.00%)  1 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  2
Alanine aminotransferase increased  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Blood alkaline phosphatase increased  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Blood creatinine phosphokinase increased  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Blood creatinine increased  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Blood glucose increased  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Blood iron decreased  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Blood pressure decreased  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Blood urea increased  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Body temperature decreased  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Body temperature increased  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
C-reactive protein increased  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Electrocardiogram QRS complex prolonged  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Electrocardiogram QT prolonged  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Haemoglobin increased  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Heart rate decreased  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Heart rate irregular  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Mean haemoglobin decreased  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
QRS axis abnormal  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Serum ferritin decreased  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Urinary lipids present  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Metabolism and nutrition disorders         
Hyponatraemia  1  1/20 (5.00%)  1 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  2
Gout  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Hyperuricaemia  1  0/20 (0.00%)  0 1/19 (5.26%)  2 0/5 (0.00%)  0 1/44 (2.27%)  2
Hypoalbuminaemia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Hypoproteinaemia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Impaired fasting glucose  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Type 2 diabetes mellitus  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Musculoskeletal and connective tissue disorders         
Pain in extremity  1  3/20 (15.00%)  3 4/19 (21.05%)  6 0/5 (0.00%)  0 7/44 (15.91%)  9
Musculoskeletal chest pain  1  2/20 (10.00%)  2 3/19 (15.79%)  4 1/5 (20.00%)  1 6/44 (13.64%)  7
Arthralgia  1  0/20 (0.00%)  0 5/19 (26.32%)  5 0/5 (0.00%)  0 5/44 (11.36%)  5
Muscle spasms  1  2/20 (10.00%)  2 3/19 (15.79%)  4 0/5 (0.00%)  0 5/44 (11.36%)  6
Back pain  1  1/20 (5.00%)  1 2/19 (10.53%)  2 1/5 (20.00%)  1 4/44 (9.09%)  4
Musculoskeletal pain  1  1/20 (5.00%)  1 1/19 (5.26%)  1 1/5 (20.00%)  1 3/44 (6.82%)  3
Myalgia  1  2/20 (10.00%)  2 1/19 (5.26%)  10 0/5 (0.00%)  0 3/44 (6.82%)  12
Muscular weakness  1  1/20 (5.00%)  2 0/19 (0.00%)  0 1/5 (20.00%)  2 2/44 (4.55%)  4
Gouty arthritis  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Intervertebral disc degeneration  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Joint stiffness  1  1/20 (5.00%)  3 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  3
Joint swelling  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Muscle tightness  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  1 1/44 (2.27%)  1
Musculoskeletal stiffness  1  1/20 (5.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  2
Osteoarthritis  1  0/20 (0.00%)  0 1/19 (5.26%)  2 0/5 (0.00%)  0 1/44 (2.27%)  2
Osteopenia  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Spinal osteoarthritis  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  1 1/44 (2.27%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Basal cell carcinoma  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  1 1/44 (2.27%)  1
Nervous system disorders         
Headache  1  2/20 (10.00%)  3 4/19 (21.05%)  6 1/5 (20.00%)  2 7/44 (15.91%)  11
Dizziness  1  2/20 (10.00%)  6 3/19 (15.79%)  4 0/5 (0.00%)  0 5/44 (11.36%)  10
Paraesthesia  1  1/20 (5.00%)  1 2/19 (10.53%)  2 2/5 (40.00%)  3 5/44 (11.36%)  6
Syncope  1  1/20 (5.00%)  1 2/19 (10.53%)  2 0/5 (0.00%)  0 3/44 (6.82%)  3
Tremor  1  1/20 (5.00%)  2 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  3
Amnesia  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Aphasia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Aphonia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Balance disorder  1  1/20 (5.00%)  3 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  3
Disturbance in attention  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Dizziness postural  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Dysgeusia  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Facial paresis  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  1 1/44 (2.27%)  1
Hyperreflexia  1  1/20 (5.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  2
Hypoaethesia  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Lethargy  1  1/20 (5.00%)  5 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  5
Loss of consciousness  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Poor quality sleep  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Sensory loss  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Spastic paralysis  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Psychiatric disorders         
Depression  1  1/20 (5.00%)  1 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  2
Alcohol abuse  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Anxiety  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Disorientation  1  1/20 (5.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  2
Renal and urinary disorders         
Dysuria  1  0/20 (0.00%)  0 3/19 (15.79%)  3 0/5 (0.00%)  0 3/44 (6.82%)  3
Haematuria  1  1/20 (5.00%)  2 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  3
Proteinuria  1  2/20 (10.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 2/44 (4.55%)  2
Renal failure chronic  1  1/20 (5.00%)  1 1/19 (5.26%)  2 0/5 (0.00%)  0 2/44 (4.55%)  3
Renal cyst  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Renal impairment  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Urinary tract obstruction  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Reproductive system and breast disorders         
Benign prostatic hyperplasia  1  2/20 (10.00%)  2 1/19 (5.26%)  1 0/5 (0.00%)  0 3/44 (6.82%)  3
Prostatitis  1  1/20 (5.00%)  1 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  2
Breast pain  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Cervical polyp  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Menopausal symptoms  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Uterine polyp  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Respiratory, thoracic and mediastinal disorders         
Cough  1  4/20 (20.00%)  5 3/19 (15.79%)  5 1/5 (20.00%)  1 8/44 (18.18%)  11
Dyspnoea  1  1/20 (5.00%)  1 2/19 (10.53%)  2 1/5 (20.00%)  1 4/44 (9.09%)  4
Asthma  1  0/20 (0.00%)  0 2/19 (10.53%)  2 0/5 (0.00%)  0 2/44 (4.55%)  2
Hyperventilation  1  1/20 (5.00%)  1 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  2
Dyspnoea exertional  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Epistaxis  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Laryngeal oedema  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Oropharyngeal pain  1  1/20 (5.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  2
Rhinorrhoea  1  1/20 (5.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  2
Skin and subcutaneous tissue disorders         
Urticaria  1  1/20 (5.00%)  1 2/19 (10.53%)  2 0/5 (0.00%)  0 3/44 (6.82%)  3
Hyperhidrosis  1  1/20 (5.00%)  2 1/19 (5.26%)  1 0/5 (0.00%)  0 2/44 (4.55%)  3
Dermatitis  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  2 1/44 (2.27%)  2
Eczema  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Exfoliative rash  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Rosacea  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Seborrhoea  1  0/20 (0.00%)  0 0/19 (0.00%)  0 1/5 (20.00%)  1 1/44 (2.27%)  1
Skin tightness  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Swelling face  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Haematoma  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Vascular disorders         
Hypotension  1  1/20 (5.00%)  1 1/19 (5.26%)  1 1/5 (20.00%)  2 3/44 (6.82%)  4
Hypertension  1  0/20 (0.00%)  0 1/19 (5.26%)  1 1/5 (20.00%)  1 2/44 (4.55%)  2
Aortic stenosis  1  1/20 (5.00%)  1 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  1
Hot flush  1  0/20 (0.00%)  0 1/19 (5.26%)  2 0/5 (0.00%)  0 1/44 (2.27%)  2
Pallor  1  0/20 (0.00%)  0 1/19 (5.26%)  1 0/5 (0.00%)  0 1/44 (2.27%)  1
Peripheral coldness  1  1/20 (5.00%)  2 0/19 (0.00%)  0 0/5 (0.00%)  0 1/44 (2.27%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
 
Results Point of Contact
Name/Title: Anna Wijatyk, MD, Medical Director
Organization: Shire Human Genetic Therapies, Inc. (Shire HGT)
Phone: 781-482-9622
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00864851     History of Changes
Other Study ID Numbers: TKT028
2007-005543-22 ( EudraCT Number )
First Submitted: March 18, 2009
First Posted: March 19, 2009
Results First Submitted: January 30, 2014
Results First Posted: June 6, 2014
Last Update Posted: December 14, 2018