ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase 3 Extension Study of the Safety and Efficacy of Aldurazyme® (Laronidase) in Mucopolysaccharidosis I (MPS I) Patients

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: NCT00146770
Recruitment Status : Completed
First Posted : September 7, 2005
Results First Posted : June 16, 2009
Last Update Posted : April 3, 2015
Sponsor:
Collaborator:
BioMarin/Genzyme LLC
Information provided by:
Sanofi

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Mucopolysaccharidosis I
Hurler's Syndrome
Hurler-Scheie Syndrome
Scheie Syndrome
Interventions Biological: Aldurazyme
Biological: placebo
Enrollment 45
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo/Aldurazyme Aldurazyme/Aldurazyme
Hide Arm/Group Description Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 182 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement in the Double-Bind Study prior to enrollment in this Extension Study. Patients received 26 weeks of Aldurazyme treatment in the Double-Blind Study and then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 208 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement prior to randomization in the Double-Blind Study.
Period Title: Overall Study
Started 23 22
Completed 18 22
Not Completed 5 0
Reason Not Completed
Adverse Event             2             0
Pregnancy             1             0
Withdrawal by Subject             2             0
Arm/Group Title Placebo/Aldurazyme Aldurazyme/Aldurazyme Total
Hide Arm/Group Description Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 182 weeks of Aldurazyme treatment. Patients received 26 weeks of Aldurazyme treatment in the Double-Blind Study and then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 208 weeks of Aldurazyme treatment. Total of all reporting groups
Overall Number of Baseline Participants 23 22 45
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants 22 participants 45 participants
<=12 years 10 12 22
13 to <= 18 years 8 3 11
19 to <= 65 years 5 7 12
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 23 participants 22 participants 45 participants
15.4  (7.63) 15.6  (8.63) 15.5  (8.04)
[1]
Measure Description: Age characteristics presented were recorded at Baseline in the Double-Blind Study.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 23 participants 22 participants 45 participants
Female
12
  52.2%
11
  50.0%
23
  51.1%
Male
11
  47.8%
11
  50.0%
22
  48.9%
[1]
Measure Description: Gender characteristics presented were recorded at Baseline in the Double-Blind Study.
Race/Ethnicity   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 23 participants 22 participants 45 participants
Caucasian 21 16 37
Black 0 0 0
Hispanic 0 4 4
Asian 1 1 2
Other 1 1 2
[1]
Measure Description: Race characteristics presented were recorded at Baseline in the Double-Blind Study.
1.Primary Outcome
Title Change From Baseline to Week 182 in Percent Predicted Forced Vital Capacity (FVC)
Hide Description Percent Predicted Forced Vital Capacity: the maximal exhaled breath volume following a maximal inhaled breath. Overall change from Baseline to Week 182 in percent predicted FVC = (observed value)/(predicted value) * 100%). A higher value indicates a greater response.
Time Frame Baseline to Week 182
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
This study enrolled patients who completed the Phase 3 Double-Blind Study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat with last value carried forward.
Arm/Group Title Placebo/Aldurazyme Aldurazyme/Aldurazyme
Hide Arm/Group Description:
Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 182 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement in the Double-Bind Study prior to enrollment in this Extension Study.
Patients received 26 weeks of Aldurazyme treatment in the Double-Blind Study and then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 208 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement prior to randomization in the Double-Blind Study.
Overall Number of Participants Analyzed 23 22
Mean (Standard Deviation)
Unit of Measure: percent predicted FVC
Baseline percentage points FVC 51.0  (13.15) 48.4  (14.85)
Week 182 percentage points FVC 47.7  (13.69) 47.2  (15.24)
Overall Change from Baseline to Week 182 -3.3  (9.07) -1.2  (6.52)
2.Primary Outcome
Title Change From Baseline to Week 182 in Six Minute Walk Test (6MWT)
Hide Description Six Minute Walk Test: Distance walked (measured in Meters) in 6 minutes. A longer distance indicates a greater response.
Time Frame Baseline to Week 182
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat with last value carried forward.
Arm/Group Title Placebo/Aldurazyme Aldurazyme/Aldurazyme
Hide Arm/Group Description:
Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 182 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement in the Double-Bind Study prior to enrollment in this Extension Study.
Patients received 26 weeks of Aldurazyme treatment in the Double-Blind Study and then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 208 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement prior to randomization in the Double-Blind Study.
Overall Number of Participants Analyzed 23 22
Mean (Standard Deviation)
Unit of Measure: Meters
Baseline distance walked 348.3  (128.81) 319.0  (131.41)
Week 182 distance walked 367.7  (151.25) 358.3  (126.40)
Overall Change from Baseline to Week 182 19.4  (107.36) 39.2  (85.84)
3.Secondary Outcome
Title Change From Baseline to Week 182 in Apnea/Hypopnea Index (AHI)
Hide Description Apnea/Hypopnea Index (AHI): Number of absent (apnea) and shallow (hypopnea) breaths per hour of sleep. A greater decrease in events indicates a greater response.
Time Frame Baseline to Week 182
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat.
Arm/Group Title Placebo/Aldurazyme Aldurazyme/Aldurazyme
Hide Arm/Group Description:
Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 182 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement in the Double-Bind Study prior to enrollment in this Extension Study.
Patients received 26 weeks of Aldurazyme treatment in the Double-Blind Study and then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 208 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement prior to randomization in the Double-Blind Study.
Overall Number of Participants Analyzed 15 17
Mean (Standard Deviation)
Unit of Measure: Events per Hour
Baseline events per hour 14.6  (12.90) 18.0  (15.54)
Week 182 events per hour 9.8  (14.60) 14.0  (19.32)
Overall Change from Baseline to Week 182 -4.8  (13.86) -4.0  (12.91)
4.Secondary Outcome
Title Change From Baseline to Week 182 in Liver Volume
Hide Description Liver Organ Volume: Volume of liver measured by Magnetic Resonance Imaging (MRI). Greater decrease in volume indicates a greater response.
Time Frame Baseline to Week 182
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat.
Arm/Group Title Placebo/Aldurazyme Aldurazyme/Aldurazyme
Hide Arm/Group Description:
Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 182 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement in the Double-Bind Study prior to enrollment in this Extension Study.
Patients received 26 weeks of Aldurazyme treatment in the Double-Blind Study and then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 208 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement prior to randomization in the Double-Blind Study.
Overall Number of Participants Analyzed 17 21
Mean (Standard Deviation)
Unit of Measure: Cubic centimeters (cm3)
Baseline liver volume (cm3) 1351.6  (323.71) 1228.5  (279.62)
Week 182 liver volume (cm3) 1079.9  (256.99) 1001.4  (157.23)
Percent Change from Baseline to Week 182 (%) -17.6  (20.21) -16.1  (14.76)
5.Secondary Outcome
Title Change From Baseline to Week 182 in Child Health Assessment Questionnaire/Health Assessment Questionnaire (CHAQ/HAQ) Disability Index Score
Hide Description CHAQ/HAQ = Patient questionnaire that measures the degree of disability on a scale of 0 (no disability) to 3 (maximal disability). A lower score indicates a greater response.
Time Frame Baseline to Week 182
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat.
Arm/Group Title Placebo/Aldurazyme Aldurazyme/Aldurazyme
Hide Arm/Group Description:
Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 182 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement in the Double-Bind Study prior to enrollment in this Extension Study.
Patients received 26 weeks of Aldurazyme treatment in the Double-Blind Study and then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 208 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement prior to randomization in the Double-Blind Study.
Overall Number of Participants Analyzed 19 20
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Baseline Score 1.75  (0.740) 1.99  (0.496)
Week 182 Score 1.49  (0.768) 1.56  (0.758)
Overall change from Baseline to Week 182 -0.26  (0.688) -0.43  (0.574)
6.Secondary Outcome
Title Change From Baseline to Week 182 in Active Joint Range of Motion (ROM)
Hide Description Active Joint Range of Motion (ROM): Shoulder Flexion Ability to maximally raise one’s arm overhead without assistance. Shoulder range of motion (mean of left and right arms) measured in degrees (0-180) by goniometry. Greater degree of flexion indicates greater response.
Time Frame Baseline to Week182
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat.
Arm/Group Title Placebo/Aldurazyme Aldurazyme/Aldurazyme
Hide Arm/Group Description:
Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 182 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement in the Double-Bind Study prior to enrollment in this Extension Study.
Patients received 26 weeks of Aldurazyme treatment in the Double-Blind Study and then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 208 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement prior to randomization in the Double-Blind Study.
Overall Number of Participants Analyzed 23 19
Mean (Standard Deviation)
Unit of Measure: Degrees
Baseline degrees 85.2  (32.66) 96.1  (30.25)
Week 182 degrees 103.5  (23.34) 109.2  (22.24)
Overall change from Baseline to Week 182 18.3  (21.59) 13.1  (20.66)
7.Other Pre-specified Outcome
Title Change From Baseline to Week 182 in Urinary GAG Level
Hide Description Urinary Glycosaminoglycan (GAG) Levels: >> Concentration of GAG relative to creatinine in urine. A greater decrease in GAG level indicates a greater response.
Time Frame Baseline to Week 182
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The study enrolled patients who completed the Phase 3 double-blind study and wished to receive open-label treatment with Aldurazyme. The analysis method was intention to treat.
Arm/Group Title Placebo/Aldurazyme Aldurazyme/Aldurazyme
Hide Arm/Group Description:
Patients received placebo for 26 weeks in the Double-Blind Study then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 182 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement in the Double-Bind Study prior to enrollment in this Extension Study.
Patients received 26 weeks of Aldurazyme treatment in the Double-Blind Study and then received 182 weeks of Aldurazyme treatment in the Extension Study; patients received a total of 208 weeks of Aldurazyme treatment. “Baseline” for this group is the last measurement prior to randomization in the Double-Blind Study.
Overall Number of Participants Analyzed 23 22
Mean (Standard Deviation)
Unit of Measure: ug GAG/mg Creatinine
Baseline level (ug GAG/mg Creatinine) 250.2  (105.09) 190.2  (59.81)
Week 182 level (ug GAG/mg Creatinine) 55.3  (30.88) 59.8  (34.99)
Percent change from Baseline to Week 182 (%) -77.0  (10.09) -66.3  (21.29)
Time Frame [Not Specified]
Adverse Event Reporting Description In the event a single participant has experienced both a serious and a non-serious form of the same adverse event term, the individual has been included in the numerator ("number of affected participants") of both adverse event tables.
 
Arm/Group Title Placebo/|Aldurazyme***Check Title*** Aldurazyme/|Aldurazyme***Check Title***
Hide Arm/Group Description Placebo/|Aldurazyme***Check Description*** Aldurazyme/|Aldurazyme***Check Description***
All-Cause Mortality
Placebo/|Aldurazyme***Check Title*** Aldurazyme/|Aldurazyme***Check Title***
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo/|Aldurazyme***Check Title*** Aldurazyme/|Aldurazyme***Check Title***
Affected / at Risk (%) Affected / at Risk (%)
Total   11/23 (47.83%)   14/22 (63.64%) 
Cardiac disorders     
Arrhythmia  1  1/23 (4.35%)  0/22 (0.00%) 
Atrial flutter  1  0/23 (0.00%)  1/22 (4.55%) 
Coronary artery stenosis  1  1/23 (4.35%)  0/22 (0.00%) 
Palpitations  1  0/23 (0.00%)  1/22 (4.55%) 
Congenital, familial and genetic disorders     
Arnold-Chiari malformation  1  1/23 (4.35%)  0/22 (0.00%) 
Talipes  1  1/23 (4.35%)  0/22 (0.00%) 
Eye disorders     
Corneal opacity  1  1/23 (4.35%)  1/22 (4.55%) 
Visual acuity reduced  1  1/23 (4.35%)  0/22 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/23 (4.35%)  1/22 (4.55%) 
Constipation  1  1/23 (4.35%)  0/22 (0.00%) 
Diarrhoea  1  1/23 (4.35%)  0/22 (0.00%) 
Dysphagia  1  1/23 (4.35%)  1/22 (4.55%) 
Inguinal hernia  1  1/23 (4.35%)  0/22 (0.00%) 
Small intestinal obstruction  1  0/23 (0.00%)  1/22 (4.55%) 
Small intestinal perforation  1  0/23 (0.00%)  1/22 (4.55%) 
Umbilical hernia  1  3/23 (13.04%)  0/22 (0.00%) 
Vomiting  1  0/23 (0.00%)  1/22 (4.55%) 
General disorders     
Catheter related complication  1  1/23 (4.35%)  0/22 (0.00%) 
Granuloma  1  0/23 (0.00%)  1/22 (4.55%) 
Hernia pain  1  1/23 (4.35%)  0/22 (0.00%) 
Pyrexia  1  0/23 (0.00%)  1/22 (4.55%) 
Immune system disorders     
Anaphylactic reaction  1  1/23 (4.35%)  0/22 (0.00%) 
Heart transplant rejection  1  1/23 (4.35%)  0/22 (0.00%) 
Infections and infestations     
Bacteraemia  1  0/23 (0.00%)  1/22 (4.55%) 
Bronchitis  1  1/23 (4.35%)  0/22 (0.00%) 
Catheter sepsis  1  0/23 (0.00%)  1/22 (4.55%) 
Clostridium difficile colitis  1  1/23 (4.35%)  0/22 (0.00%) 
Herpes virus infection  1  1/23 (4.35%)  0/22 (0.00%) 
Lobar pneumonia  1  0/23 (0.00%)  1/22 (4.55%) 
Otitis media  1  0/23 (0.00%)  1/22 (4.55%) 
Pneumonia  1  1/23 (4.35%)  0/22 (0.00%) 
Sepsis  1  0/23 (0.00%)  1/22 (4.55%) 
Tracheitis  1  1/23 (4.35%)  0/22 (0.00%) 
Upper respiratory tract infection  1  1/23 (4.35%)  0/22 (0.00%) 
Injury, poisoning and procedural complications     
Procedural pain  1  0/23 (0.00%)  1/22 (4.55%) 
Subdural haematoma  1  0/23 (0.00%)  1/22 (4.55%) 
Investigations     
Blood pressure increased  1  1/23 (4.35%)  0/22 (0.00%) 
Electroencephalogram abnormal  1  0/23 (0.00%)  1/22 (4.55%) 
Oxygen saturation decreased  1  0/23 (0.00%)  1/22 (4.55%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/23 (0.00%)  1/22 (4.55%) 
Cervical spinal stenosis  1  1/23 (4.35%)  1/22 (4.55%) 
Muscular weakness  1  0/23 (0.00%)  1/22 (4.55%) 
Tendon disorder  1  0/23 (0.00%)  2/22 (9.09%) 
Nervous system disorders     
Carpal tunnel syndrome  1  0/23 (0.00%)  1/22 (4.55%) 
Cervical cord compression  1  0/23 (0.00%)  1/22 (4.55%) 
Convulsion  1  0/23 (0.00%)  2/22 (9.09%) 
Extensor plantar response  1  1/23 (4.35%)  0/22 (0.00%) 
Grand mal convulsion  1  0/23 (0.00%)  1/22 (4.55%) 
Hydrocephalus  1  0/23 (0.00%)  1/22 (4.55%) 
Intracranial pressure increased  1  0/23 (0.00%)  1/22 (4.55%) 
Myoclonus  1  0/23 (0.00%)  1/22 (4.55%) 
Spinal cord compression  1  0/23 (0.00%)  1/22 (4.55%) 
Psychiatric disorders     
Bipolar disorder  1  1/23 (4.35%)  0/22 (0.00%) 
Major depression  1  1/23 (4.35%)  0/22 (0.00%) 
Mental status changes  1  1/23 (4.35%)  0/22 (0.00%) 
Psychotic disorder  1  0/23 (0.00%)  1/22 (4.55%) 
Reproductive system and breast disorders     
Testicular torsion  1  0/23 (0.00%)  1/22 (4.55%) 
Respiratory, thoracic and mediastinal disorders     
Asthma  1  1/23 (4.35%)  0/22 (0.00%) 
Choking  1  1/23 (4.35%)  0/22 (0.00%) 
Dyspnoea  1  1/23 (4.35%)  0/22 (0.00%) 
Dyspnoea exertional  1  1/23 (4.35%)  0/22 (0.00%) 
Pulmonary oedema  1  1/23 (4.35%)  0/22 (0.00%) 
Respiratory disorder  1  1/23 (4.35%)  0/22 (0.00%) 
Respiratory distress  1  1/23 (4.35%)  0/22 (0.00%) 
Sleep apnoea syndrome  1  0/23 (0.00%)  2/22 (9.09%) 
Tachypnoea  1  1/23 (4.35%)  0/22 (0.00%) 
Surgical and medical procedures     
Carpal tunnel decompression  1  0/23 (0.00%)  1/22 (4.55%) 
Catheterisation venous  1  1/23 (4.35%)  0/22 (0.00%) 
Central venous catheterisation  1  1/23 (4.35%)  1/22 (4.55%) 
Vascular disorders     
Hypotension  1  0/23 (0.00%)  1/22 (4.55%) 
Poor venous access  1  0/23 (0.00%)  1/22 (4.55%) 
Thrombosis  1  0/23 (0.00%)  1/22 (4.55%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Placebo/|Aldurazyme***Check Title*** Aldurazyme/|Aldurazyme***Check Title***
Affected / at Risk (%) Affected / at Risk (%)
Total   23/23 (100.00%)   22/22 (100.00%) 
Blood and lymphatic system disorders     
Lymphadenopathy  1  5/23 (21.74%)  2/22 (9.09%) 
Splenomegaly  1  2/23 (8.70%)  4/22 (18.18%) 
Cardiac disorders     
Angina pectoris  1  0/23 (0.00%)  1/22 (4.55%) 
Aortic valve incompetence  1  3/23 (13.04%)  2/22 (9.09%) 
Arrhythmia  1  1/23 (4.35%)  2/22 (9.09%) 
Atrioventricular block first degree  1  2/23 (8.70%)  2/22 (9.09%) 
Atrioventricular block second degree  1  1/23 (4.35%)  0/22 (0.00%) 
Bradycardia  1  0/23 (0.00%)  1/22 (4.55%) 
Coronary artery stenosis  1  1/23 (4.35%)  0/22 (0.00%) 
Cyanosis  1  0/23 (0.00%)  1/22 (4.55%) 
Extrasystoles  1  0/23 (0.00%)  2/22 (9.09%) 
Left atrial dilatation  1  1/23 (4.35%)  2/22 (9.09%) 
Left ventricular dysfunction  1  2/23 (8.70%)  0/22 (0.00%) 
Left ventricular hypertrophy  1  2/23 (8.70%)  0/22 (0.00%) 
Mitral valve disease  1  0/23 (0.00%)  1/22 (4.55%) 
Mitral valve incompetence  1  1/23 (4.35%)  1/22 (4.55%) 
Mitral valve stenosis  1  1/23 (4.35%)  0/22 (0.00%) 
Myocarditis  1  1/23 (4.35%)  0/22 (0.00%) 
Palpitations  1  1/23 (4.35%)  2/22 (9.09%) 
Pericardial disease  1  2/23 (8.70%)  0/22 (0.00%) 
Sinus arrhythmia  1  0/23 (0.00%)  1/22 (4.55%) 
Tachycardia  1  2/23 (8.70%)  1/22 (4.55%) 
Ventricular extrasystoles  1  0/23 (0.00%)  1/22 (4.55%) 
Congenital, familial and genetic disorders     
Hip dysplasia  1  1/23 (4.35%)  0/22 (0.00%) 
Odontogenic cyst  1  0/23 (0.00%)  1/22 (4.55%) 
Talipes  1  3/23 (13.04%)  2/22 (9.09%) 
Ear and labyrinth disorders     
Cerumen impaction  1  3/23 (13.04%)  2/22 (9.09%) 
Deafness  1  0/23 (0.00%)  1/22 (4.55%) 
Deafness bilateral  1  0/23 (0.00%)  1/22 (4.55%) 
Deafness unilateral  1  1/23 (4.35%)  0/22 (0.00%) 
Ear discomfort  1  1/23 (4.35%)  2/22 (9.09%) 
Ear disorder  1  1/23 (4.35%)  0/22 (0.00%) 
Ear haemorrhage  1  0/23 (0.00%)  2/22 (9.09%) 
Ear pain  1  7/23 (30.43%)  11/22 (50.00%) 
Ear pruritus  1  1/23 (4.35%)  1/22 (4.55%) 
Hypoacusis  1  1/23 (4.35%)  1/22 (4.55%) 
Inner ear inflammation  1  0/23 (0.00%)  2/22 (9.09%) 
Middle ear effusion  1  1/23 (4.35%)  0/22 (0.00%) 
Motion sickness  1  1/23 (4.35%)  0/22 (0.00%) 
Otorrhoea  1  4/23 (17.39%)  3/22 (13.64%) 
Tinnitus  1  2/23 (8.70%)  0/22 (0.00%) 
Tympanic membrane hyperaemia  1  1/23 (4.35%)  0/22 (0.00%) 
Tympanic membrane perforation  1  1/23 (4.35%)  1/22 (4.55%) 
Tympanic membrane scarring  1  1/23 (4.35%)  0/22 (0.00%) 
Vertigo  1  2/23 (8.70%)  2/22 (9.09%) 
Endocrine disorders     
Cushingoid  1  1/23 (4.35%)  0/22 (0.00%) 
Hypothyroidism  1  1/23 (4.35%)  0/22 (0.00%) 
Eye disorders     
Abnormal sensation in eye  1  1/23 (4.35%)  0/22 (0.00%) 
Anisometropia  1  1/23 (4.35%)  0/22 (0.00%) 
Astigmatism  1  1/23 (4.35%)  1/22 (4.55%) 
Blepharospasm  1  1/23 (4.35%)  0/22 (0.00%) 
Conjunctival hyperaemia  1  1/23 (4.35%)  0/22 (0.00%) 
Conjunctivitis  1  1/23 (4.35%)  3/22 (13.64%) 
Corneal oedema  1  1/23 (4.35%)  0/22 (0.00%) 
Corneal opacity  1  2/23 (8.70%)  5/22 (22.73%) 
Dry eye  1  0/23 (0.00%)  1/22 (4.55%) 
Eye allergy  1  0/23 (0.00%)  1/22 (4.55%) 
Eye inflammation  1  0/23 (0.00%)  1/22 (4.55%) 
Eye irritation  1  1/23 (4.35%)  2/22 (9.09%) 
Eye movement disorder  1  0/23 (0.00%)  1/22 (4.55%) 
Eye oedema  1  1/23 (4.35%)  0/22 (0.00%) 
Eye pain  1  2/23 (8.70%)  2/22 (9.09%) 
Eye pruritus  1  2/23 (8.70%)  1/22 (4.55%) 
Eye swelling  1  0/23 (0.00%)  1/22 (4.55%) 
Eyelid oedema  1  0/23 (0.00%)  1/22 (4.55%) 
Hypermetropia  1  1/23 (4.35%)  1/22 (4.55%) 
Hypoaesthesia eye  1  1/23 (4.35%)  0/22 (0.00%) 
Lacrimation increased  1  2/23 (8.70%)  4/22 (18.18%) 
Myodesopsia  1  1/23 (4.35%)  0/22 (0.00%) 
Myopia  1  0/23 (0.00%)  1/22 (4.55%) 
Ocular hyperaemia  1  0/23 (0.00%)  1/22 (4.55%) 
Optic atrophy  1  0/23 (0.00%)  1/22 (4.55%) 
Papilloedema  1  1/23 (4.35%)  0/22 (0.00%) 
Photophobia  1  0/23 (0.00%)  1/22 (4.55%) 
Pseudopapilloedema  1  0/23 (0.00%)  1/22 (4.55%) 
Pterygium  1  0/23 (0.00%)  1/22 (4.55%) 
Retinal degeneration  1  1/23 (4.35%)  1/22 (4.55%) 
Retinal pigment epitheliopathy  1  2/23 (8.70%)  1/22 (4.55%) 
Strabismus  1  1/23 (4.35%)  1/22 (4.55%) 
Vision blurred  1  3/23 (13.04%)  1/22 (4.55%) 
Visual acuity reduced  1  1/23 (4.35%)  2/22 (9.09%) 
Gastrointestinal disorders     
Abdominal discomfort  1  3/23 (13.04%)  1/22 (4.55%) 
Abdominal distension  1  0/23 (0.00%)  4/22 (18.18%) 
Abdominal pain  1  7/23 (30.43%)  9/22 (40.91%) 
Abdominal pain lower  1  2/23 (8.70%)  3/22 (13.64%) 
Abdominal pain upper  1  7/23 (30.43%)  8/22 (36.36%) 
Abdominal strangulated hernia  1  0/23 (0.00%)  1/22 (4.55%) 
Aphthous stomatitis  1  0/23 (0.00%)  1/22 (4.55%) 
Constipation  1  2/23 (8.70%)  5/22 (22.73%) 
Dental caries  1  0/23 (0.00%)  1/22 (4.55%) 
Diarrhoea  1  14/23 (60.87%)  10/22 (45.45%) 
Dry mouth  1  1/23 (4.35%)  1/22 (4.55%) 
Dyspepsia  1  0/23 (0.00%)  2/22 (9.09%) 
Dysphagia  1  1/23 (4.35%)  2/22 (9.09%) 
Faecal incontinence  1  0/23 (0.00%)  1/22 (4.55%) 
Faeces discoloured  1  1/23 (4.35%)  0/22 (0.00%) 
Flatulence  1  1/23 (4.35%)  0/22 (0.00%) 
Gastrointestinal disorder  1  2/23 (8.70%)  1/22 (4.55%) 
Gastrointestinal hypermotility  1  0/23 (0.00%)  1/22 (4.55%) 
Gastrooesophageal reflux disease  1  1/23 (4.35%)  0/22 (0.00%) 
Gingival cyst  1  1/23 (4.35%)  1/22 (4.55%) 
Gingival hyperplasia  1  0/23 (0.00%)  1/22 (4.55%) 
Haematochezia  1  1/23 (4.35%)  0/22 (0.00%) 
Haemorrhoids  1  1/23 (4.35%)  0/22 (0.00%) 
Inguinal hernia  1  2/23 (8.70%)  1/22 (4.55%) 
Lip blister  1  0/23 (0.00%)  1/22 (4.55%) 
Lip swelling  1  1/23 (4.35%)  0/22 (0.00%) 
Lip ulceration  1  1/23 (4.35%)  0/22 (0.00%) 
Megacolon  1  1/23 (4.35%)  0/22 (0.00%) 
Nausea  1  16/23 (69.57%)  12/22 (54.55%) 
Oesophageal disorder  1  0/23 (0.00%)  1/22 (4.55%) 
Oral pain  1  1/23 (4.35%)  1/22 (4.55%) 
Salivary hypersecretion  1  1/23 (4.35%)  1/22 (4.55%) 
Small intestinal obstruction  1  0/23 (0.00%)  1/22 (4.55%) 
Stomach discomfort  1  2/23 (8.70%)  0/22 (0.00%) 
Teething  1  1/23 (4.35%)  0/22 (0.00%) 
Tongue disorder  1  0/23 (0.00%)  1/22 (4.55%) 
Tooth disorder  1  2/23 (8.70%)  1/22 (4.55%) 
Tooth loss  1  0/23 (0.00%)  1/22 (4.55%) 
Toothache  1  6/23 (26.09%)  2/22 (9.09%) 
Umbilical hernia  1  2/23 (8.70%)  3/22 (13.64%) 
Vomiting  1  13/23 (56.52%)  12/22 (54.55%) 
General disorders     
Application site erythema  1  1/23 (4.35%)  0/22 (0.00%) 
Application site pruritus  1  0/23 (0.00%)  1/22 (4.55%) 
Application site rash  1  0/23 (0.00%)  1/22 (4.55%) 
Asthenia  1  2/23 (8.70%)  1/22 (4.55%) 
Catheter related complication  1  2/23 (8.70%)  0/22 (0.00%) 
Catheter site discharge  1  1/23 (4.35%)  0/22 (0.00%) 
Catheter site erythema  1  1/23 (4.35%)  0/22 (0.00%) 
Catheter site inflammation  1  2/23 (8.70%)  1/22 (4.55%) 
Catheter site pain  1  3/23 (13.04%)  3/22 (13.64%) 
Catheter site pruritus  1  1/23 (4.35%)  1/22 (4.55%) 
Catheter site rash  1  0/23 (0.00%)  2/22 (9.09%) 
Catheter site related reaction  1  4/23 (17.39%)  1/22 (4.55%) 
Catheter site swelling  1  0/23 (0.00%)  1/22 (4.55%) 
Catheter site urticaria  1  0/23 (0.00%)  1/22 (4.55%) 
Chest discomfort  1  2/23 (8.70%)  2/22 (9.09%) 
Chest pain  1  6/23 (26.09%)  7/22 (31.82%) 
Chills  1  2/23 (8.70%)  2/22 (9.09%) 
Cyst  1  1/23 (4.35%)  2/22 (9.09%) 
Fatigue  1  6/23 (26.09%)  9/22 (40.91%) 
Feeling cold  1  2/23 (8.70%)  1/22 (4.55%) 
Feeling hot  1  3/23 (13.04%)  3/22 (13.64%) 
Feeling of body temperature change  1  2/23 (8.70%)  0/22 (0.00%) 
Gait disturbance  1  6/23 (26.09%)  3/22 (13.64%) 
Granuloma  1  0/23 (0.00%)  1/22 (4.55%) 
Hangover  1  1/23 (4.35%)  0/22 (0.00%) 
Hernia pain  1  1/23 (4.35%)  2/22 (9.09%) 
Hyperthermia  1  1/23 (4.35%)  0/22 (0.00%) 
Hypothermia  1  1/23 (4.35%)  0/22 (0.00%) 
Inflammation  1  0/23 (0.00%)  2/22 (9.09%) 
Influenza like illness  1  3/23 (13.04%)  5/22 (22.73%) 
Infusion site erythema  1  2/23 (8.70%)  1/22 (4.55%) 
Infusion site extravasation  1  4/23 (17.39%)  4/22 (18.18%) 
Infusion site pain  1  3/23 (13.04%)  2/22 (9.09%) 
Infusion site reaction  1  0/23 (0.00%)  1/22 (4.55%) 
Injection site haematoma  1  1/23 (4.35%)  1/22 (4.55%) 
Irritability  1  1/23 (4.35%)  0/22 (0.00%) 
Local swelling  1  1/23 (4.35%)  1/22 (4.55%) 
Malaise  1  1/23 (4.35%)  2/22 (9.09%) 
Oedema peripheral  1  2/23 (8.70%)  4/22 (18.18%) 
Pain  1  3/23 (13.04%)  4/22 (18.18%) 
Pyrexia  1  16/23 (69.57%)  18/22 (81.82%) 
Secretion discharge  1  0/23 (0.00%)  1/22 (4.55%) 
Hepatobiliary disorders     
Hepatomegaly  1  5/23 (21.74%)  8/22 (36.36%) 
Hepatosplenomegaly  1  0/23 (0.00%)  1/22 (4.55%) 
Immune system disorders     
Corneal graft rejection  1  2/23 (8.70%)  1/22 (4.55%) 
Food allergy  1  1/23 (4.35%)  0/22 (0.00%) 
Multiple allergies  1  0/23 (0.00%)  1/22 (4.55%) 
Seasonal allergy  1  2/23 (8.70%)  3/22 (13.64%) 
Infections and infestations     
Bronchiolitis  1  1/23 (4.35%)  0/22 (0.00%) 
Bronchitis  1  2/23 (8.70%)  1/22 (4.55%) 
Central line infection  1  1/23 (4.35%)  0/22 (0.00%) 
Conjunctivitis infective  1  0/23 (0.00%)  1/22 (4.55%) 
Cystitis  1  2/23 (8.70%)  0/22 (0.00%) 
Dacryocystitis  1  1/23 (4.35%)  0/22 (0.00%) 
Ear infection  1  10/23 (43.48%)  7/22 (31.82%) 
Enterobiasis  1  0/23 (0.00%)  1/22 (4.55%) 
Eye infection  1  1/23 (4.35%)  1/22 (4.55%) 
Fungal infection  1  0/23 (0.00%)  1/22 (4.55%) 
Fungal skin infection  1  1/23 (4.35%)  0/22 (0.00%) 
Furuncle  1  0/23 (0.00%)  1/22 (4.55%) 
Gastroenteritis  1  3/23 (13.04%)  0/22 (0.00%) 
Gastroenteritis viral  1  4/23 (17.39%)  1/22 (4.55%) 
Herpangina  1  1/23 (4.35%)  0/22 (0.00%) 
Herpes virus infection  1  0/23 (0.00%)  1/22 (4.55%) 
Herpes zoster  1  0/23 (0.00%)  1/22 (4.55%) 
Hordeolum  1  3/23 (13.04%)  0/22 (0.00%) 
Infectious mononucleosis  1  0/23 (0.00%)  1/22 (4.55%) 
Influenza  1  6/23 (26.09%)  1/22 (4.55%) 
Laryngitis  1  1/23 (4.35%)  0/22 (0.00%) 
Lice infestation  1  1/23 (4.35%)  1/22 (4.55%) 
Lower respiratory tract infection  1  3/23 (13.04%)  4/22 (18.18%) 
Lymph gland infection  1  1/23 (4.35%)  0/22 (0.00%) 
Myringitis  1  0/23 (0.00%)  1/22 (4.55%) 
Nasopharyngitis  1  19/23 (82.61%)  17/22 (77.27%) 
Oral herpes  1  1/23 (4.35%)  1/22 (4.55%) 
Otitis externa  1  5/23 (21.74%)  3/22 (13.64%) 
Otitis media  1  5/23 (21.74%)  6/22 (27.27%) 
Otitis media acute  1  0/23 (0.00%)  2/22 (9.09%) 
Otitis media chronic  1  2/23 (8.70%)  0/22 (0.00%) 
Paronychia  1  1/23 (4.35%)  0/22 (0.00%) 
Pharyngitis  1  3/23 (13.04%)  2/22 (9.09%) 
Pharyngitis streptococcal  1  3/23 (13.04%)  1/22 (4.55%) 
Pneumonia  1  2/23 (8.70%)  3/22 (13.64%) 
Postoperative wound infection  1  2/23 (8.70%)  0/22 (0.00%) 
Respiratory tract infection  1  1/23 (4.35%)  1/22 (4.55%) 
Rhinitis  1  4/23 (17.39%)  6/22 (27.27%) 
Sialoadenitis  1  1/23 (4.35%)  1/22 (4.55%) 
Sinusitis  1  4/23 (17.39%)  2/22 (9.09%) 
Skin infection  1  1/23 (4.35%)  1/22 (4.55%) 
Tinea pedis  1  1/23 (4.35%)  2/22 (9.09%) 
Tooth abscess  1  2/23 (8.70%)  1/22 (4.55%) 
Tracheobronchitis  1  0/23 (0.00%)  1/22 (4.55%) 
Upper respiratory tract infection  1  6/23 (26.09%)  7/22 (31.82%) 
Upper respiratory tract infection bacterial  1  0/23 (0.00%)  1/22 (4.55%) 
Urinary tract infection  1  4/23 (17.39%)  3/22 (13.64%) 
Viral diarrhoea  1  1/23 (4.35%)  0/22 (0.00%) 
Viral infection  1  2/23 (8.70%)  2/22 (9.09%) 
Viral pharyngitis  1  0/23 (0.00%)  1/22 (4.55%) 
Viral skin infection  1  1/23 (4.35%)  0/22 (0.00%) 
Viral upper respiratory tract infection  1  3/23 (13.04%)  3/22 (13.64%) 
Vulvovaginal candidiasis  1  0/23 (0.00%)  1/22 (4.55%) 
Injury, poisoning and procedural complications     
Arthropod bite  1  1/23 (4.35%)  1/22 (4.55%) 
Back injury  1  0/23 (0.00%)  1/22 (4.55%) 
Bite  1  1/23 (4.35%)  0/22 (0.00%) 
Contusion  1  4/23 (17.39%)  5/22 (22.73%) 
Device migration  1  1/23 (4.35%)  0/22 (0.00%) 
Endotracheal intubation complication  1  1/23 (4.35%)  0/22 (0.00%) 
Excoriation  1  2/23 (8.70%)  3/22 (13.64%) 
Extrusion of device  1  0/23 (0.00%)  1/22 (4.55%) 
Fall  1  6/23 (26.09%)  3/22 (13.64%) 
Incision site pain  1  0/23 (0.00%)  2/22 (9.09%) 
Joint injury  1  1/23 (4.35%)  2/22 (9.09%) 
Limb injury  1  0/23 (0.00%)  1/22 (4.55%) 
Medical device complication  1  0/23 (0.00%)  1/22 (4.55%) 
Mouth injury  1  1/23 (4.35%)  1/22 (4.55%) 
Muscle strain  1  1/23 (4.35%)  2/22 (9.09%) 
Nail avulsion  1  0/23 (0.00%)  1/22 (4.55%) 
Neck injury  1  0/23 (0.00%)  1/22 (4.55%) 
Post procedural complication  1  0/23 (0.00%)  1/22 (4.55%) 
Post-traumatic pain  1  0/23 (0.00%)  1/22 (4.55%) 
Procedural nausea  1  1/23 (4.35%)  0/22 (0.00%) 
Procedural pain  1  7/23 (30.43%)  9/22 (40.91%) 
Procedural vomiting  1  0/23 (0.00%)  2/22 (9.09%) 
Radius fracture  1  1/23 (4.35%)  0/22 (0.00%) 
Respiratory fume inhalation disorder  1  1/23 (4.35%)  0/22 (0.00%) 
Road traffic accident  1  2/23 (8.70%)  0/22 (0.00%) 
Scratch  1  1/23 (4.35%)  2/22 (9.09%) 
Shunt malfunction  1  0/23 (0.00%)  2/22 (9.09%) 
Skin laceration  1  1/23 (4.35%)  1/22 (4.55%) 
Soft tissue injury  1  0/23 (0.00%)  1/22 (4.55%) 
Stress fracture  1  0/23 (0.00%)  1/22 (4.55%) 
Sunburn  1  1/23 (4.35%)  1/22 (4.55%) 
Thermal burn  1  1/23 (4.35%)  0/22 (0.00%) 
Tooth fracture  1  1/23 (4.35%)  1/22 (4.55%) 
Traumatic haematoma  1  1/23 (4.35%)  0/22 (0.00%) 
Vena cava injury  1  1/23 (4.35%)  0/22 (0.00%) 
Wound  1  2/23 (8.70%)  1/22 (4.55%) 
Investigations     
Aspartate aminotransferase increased  1  0/23 (0.00%)  1/22 (4.55%) 
Bacteria urine  1  0/23 (0.00%)  1/22 (4.55%) 
Blood bilirubin increased  1  0/23 (0.00%)  1/22 (4.55%) 
Blood calcium increased  1  1/23 (4.35%)  0/22 (0.00%) 
Blood cholesterol increased  1  1/23 (4.35%)  0/22 (0.00%) 
Blood iron decreased  1  4/23 (17.39%)  0/22 (0.00%) 
Blood pressure decreased  1  0/23 (0.00%)  2/22 (9.09%) 
Blood pressure diastolic decreased  1  1/23 (4.35%)  0/22 (0.00%) 
Body temperature increased  1  4/23 (17.39%)  4/22 (18.18%) 
Breath sounds abnormal  1  0/23 (0.00%)  2/22 (9.09%) 
Cardiac murmur  1  5/23 (21.74%)  8/22 (36.36%) 
Electrocardiogram PR prolongation  1  3/23 (13.04%)  1/22 (4.55%) 
Electrocardiogram QRS complex abnormal  1  1/23 (4.35%)  0/22 (0.00%) 
Electrocardiogram QT prolonged  1  1/23 (4.35%)  3/22 (13.64%) 
Eosinophil count increased  1  0/23 (0.00%)  1/22 (4.55%) 
Fungus stool identified  1  0/23 (0.00%)  1/22 (4.55%) 
Grip strength decreased  1  1/23 (4.35%)  0/22 (0.00%) 
Heart sounds abnormal  1  1/23 (4.35%)  0/22 (0.00%) 
Intraocular pressure increased  1  1/23 (4.35%)  0/22 (0.00%) 
Mean cell haemoglobin decreased  1  1/23 (4.35%)  0/22 (0.00%) 
Oxygen saturation decreased  1  1/23 (4.35%)  2/22 (9.09%) 
Renal function test abnormal  1  1/23 (4.35%)  0/22 (0.00%) 
Respiratory rate increased  1  1/23 (4.35%)  0/22 (0.00%) 
Tandem gait test abnormal  1  0/23 (0.00%)  1/22 (4.55%) 
Urine analysis abnormal  1  0/23 (0.00%)  1/22 (4.55%) 
Urine leukocyte esterase positive  1  1/23 (4.35%)  0/22 (0.00%) 
Weight decreased  1  1/23 (4.35%)  1/22 (4.55%) 
Weight increased  1  3/23 (13.04%)  1/22 (4.55%) 
White blood cells urine positive  1  2/23 (8.70%)  1/22 (4.55%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/23 (0.00%)  1/22 (4.55%) 
Dehydration  1  0/23 (0.00%)  1/22 (4.55%) 
Fluid retention  1  1/23 (4.35%)  0/22 (0.00%) 
Hypercholesterolaemia  1  0/23 (0.00%)  1/22 (4.55%) 
Hypernatraemia  1  1/23 (4.35%)  0/22 (0.00%) 
Hypokalaemia  1  0/23 (0.00%)  1/22 (4.55%) 
Hypomagnesaemia  1  0/23 (0.00%)  1/22 (4.55%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  14/23 (60.87%)  13/22 (59.09%) 
Arthropathy  1  2/23 (8.70%)  2/22 (9.09%) 
Back pain  1  12/23 (52.17%)  11/22 (50.00%) 
Bone pain  1  1/23 (4.35%)  1/22 (4.55%) 
Cervical spinal stenosis  1  0/23 (0.00%)  1/22 (4.55%) 
Extraskeletal ossification  1  1/23 (4.35%)  1/22 (4.55%) 
Flank pain  1  1/23 (4.35%)  0/22 (0.00%) 
Foot deformity  1  1/23 (4.35%)  0/22 (0.00%) 
Groin pain  1  1/23 (4.35%)  1/22 (4.55%) 
Growth retardation  1  1/23 (4.35%)  0/22 (0.00%) 
Inguinal mass  1  0/23 (0.00%)  1/22 (4.55%) 
Joint crepitation  1  4/23 (17.39%)  2/22 (9.09%) 
Joint effusion  1  1/23 (4.35%)  0/22 (0.00%) 
Joint instability  1  1/23 (4.35%)  0/22 (0.00%) 
Joint lock  1  1/23 (4.35%)  0/22 (0.00%) 
Joint range of motion decreased  1  2/23 (8.70%)  4/22 (18.18%) 
Joint stiffness  1  1/23 (4.35%)  0/22 (0.00%) 
Joint swelling  1  1/23 (4.35%)  2/22 (9.09%) 
Joint warmth  1  1/23 (4.35%)  0/22 (0.00%) 
Limb discomfort  1  1/23 (4.35%)  0/22 (0.00%) 
Lordosis  1  0/23 (0.00%)  1/22 (4.55%) 
Lower limb deformity  1  0/23 (0.00%)  1/22 (4.55%) 
Muscle atrophy  1  1/23 (4.35%)  1/22 (4.55%) 
Muscle contracture  1  1/23 (4.35%)  0/22 (0.00%) 
Muscle spasms  1  4/23 (17.39%)  2/22 (9.09%) 
Muscle tightness  1  0/23 (0.00%)  1/22 (4.55%) 
Muscle twitching  1  1/23 (4.35%)  2/22 (9.09%) 
Muscular weakness  1  3/23 (13.04%)  2/22 (9.09%) 
Musculoskeletal chest pain  1  3/23 (13.04%)  1/22 (4.55%) 
Musculoskeletal discomfort  1  1/23 (4.35%)  0/22 (0.00%) 
Musculoskeletal pain  1  11/23 (47.83%)  7/22 (31.82%) 
Musculoskeletal stiffness  1  2/23 (8.70%)  5/22 (22.73%) 
Myalgia  1  7/23 (30.43%)  4/22 (18.18%) 
Neck pain  1  5/23 (21.74%)  9/22 (40.91%) 
Pain in extremity  1  18/23 (78.26%)  14/22 (63.64%) 
Pain in jaw  1  1/23 (4.35%)  0/22 (0.00%) 
Sensation of heaviness  1  1/23 (4.35%)  0/22 (0.00%) 
Soft tissue disorder  1  1/23 (4.35%)  0/22 (0.00%) 
Tendon pain  1  0/23 (0.00%)  1/22 (4.55%) 
Tendonitis  1  1/23 (4.35%)  1/22 (4.55%) 
Trigger finger  1  0/23 (0.00%)  1/22 (4.55%) 
Unequal limb length  1  1/23 (4.35%)  0/22 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cholesteatoma  1  0/23 (0.00%)  1/22 (4.55%) 
Melanocytic naevus  1  1/23 (4.35%)  1/22 (4.55%) 
Nervous system disorders     
Aphonia  1  0/23 (0.00%)  1/22 (4.55%) 
Carpal tunnel syndrome  1  3/23 (13.04%)  3/22 (13.64%) 
Cervical cord compression  1  0/23 (0.00%)  1/22 (4.55%) 
Cervical root pain  1  1/23 (4.35%)  0/22 (0.00%) 
Clonus  1  1/23 (4.35%)  2/22 (9.09%) 
Clumsiness  1  1/23 (4.35%)  0/22 (0.00%) 
Convulsion  1  0/23 (0.00%)  2/22 (9.09%) 
Coordination abnormal  1  1/23 (4.35%)  0/22 (0.00%) 
Dizziness  1  9/23 (39.13%)  5/22 (22.73%) 
Dizziness postural  1  1/23 (4.35%)  0/22 (0.00%) 
Dyskinesia  1  0/23 (0.00%)  1/22 (4.55%) 
Grand mal convulsion  1  0/23 (0.00%)  1/22 (4.55%) 
Head discomfort  1  0/23 (0.00%)  1/22 (4.55%) 
Headache  1  19/23 (82.61%)  19/22 (86.36%) 
Hoffmann's sign  1  0/23 (0.00%)  2/22 (9.09%) 
Hyperreflexia  1  4/23 (17.39%)  6/22 (27.27%) 
Hypertonia  1  2/23 (8.70%)  1/22 (4.55%) 
Hypoaesthesia  1  3/23 (13.04%)  4/22 (18.18%) 
Hyporeflexia  1  0/23 (0.00%)  2/22 (9.09%) 
Intracranial pressure increased  1  0/23 (0.00%)  1/22 (4.55%) 
Irregular sleep phase  1  1/23 (4.35%)  0/22 (0.00%) 
Lethargy  1  3/23 (13.04%)  2/22 (9.09%) 
Loss of consciousness  1  1/23 (4.35%)  0/22 (0.00%) 
Loss of proprioception  1  0/23 (0.00%)  1/22 (4.55%) 
Migraine  1  3/23 (13.04%)  3/22 (13.64%) 
Myoclonus  1  0/23 (0.00%)  1/22 (4.55%) 
Nervous system disorder  1  0/23 (0.00%)  1/22 (4.55%) 
Neuralgia  1  1/23 (4.35%)  1/22 (4.55%) 
Neuropathy peripheral  1  0/23 (0.00%)  1/22 (4.55%) 
Nystagmus  1  0/23 (0.00%)  1/22 (4.55%) 
Paraesthesia  1  2/23 (8.70%)  4/22 (18.18%) 
Poor quality sleep  1  0/23 (0.00%)  1/22 (4.55%) 
Post-traumatic headache  1  1/23 (4.35%)  0/22 (0.00%) 
Psychomotor hyperactivity  1  0/23 (0.00%)  1/22 (4.55%) 
Reflexes abnormal  1  1/23 (4.35%)  0/22 (0.00%) 
Sensory disturbance  1  2/23 (8.70%)  1/22 (4.55%) 
Sensory loss  1  1/23 (4.35%)  0/22 (0.00%) 
Sinus headache  1  1/23 (4.35%)  0/22 (0.00%) 
Somnolence  1  3/23 (13.04%)  2/22 (9.09%) 
Speech disorder  1  0/23 (0.00%)  1/22 (4.55%) 
Syncope  1  1/23 (4.35%)  2/22 (9.09%) 
Tremor  1  0/23 (0.00%)  1/22 (4.55%) 
Psychiatric disorders     
Agitation  1  1/23 (4.35%)  0/22 (0.00%) 
Anxiety  1  3/23 (13.04%)  1/22 (4.55%) 
Apathy  1  0/23 (0.00%)  1/22 (4.55%) 
Bipolar disorder  1  1/23 (4.35%)  0/22 (0.00%) 
Daydreaming  1  0/23 (0.00%)  1/22 (4.55%) 
Depression  1  1/23 (4.35%)  4/22 (18.18%) 
Disorientation  1  0/23 (0.00%)  1/22 (4.55%) 
Flat affect  1  1/23 (4.35%)  0/22 (0.00%) 
Insomnia  1  1/23 (4.35%)  5/22 (22.73%) 
Major depression  1  1/23 (4.35%)  0/22 (0.00%) 
Mental status changes  1  0/23 (0.00%)  1/22 (4.55%) 
Restlessness  1  1/23 (4.35%)  0/22 (0.00%) 
Sleep disorder  1  0/23 (0.00%)  2/22 (9.09%) 
Renal and urinary disorders     
Bilirubinuria  1  0/23 (0.00%)  1/22 (4.55%) 
Dysuria  1  1/23 (4.35%)  2/22 (9.09%) 
Enuresis  1  0/23 (0.00%)  1/22 (4.55%) 
Ketonuria  1  0/23 (0.00%)  1/22 (4.55%) 
Micturition urgency  1  0/23 (0.00%)  1/22 (4.55%) 
Pollakiuria  1  1/23 (4.35%)  0/22 (0.00%) 
Polyuria  1  0/23 (0.00%)  1/22 (4.55%) 
Urinary incontinence  1  0/23 (0.00%)  2/22 (9.09%) 
Urinary retention  1  1/23 (4.35%)  0/22 (0.00%) 
Urinary tract pain  1  0/23 (0.00%)  1/22 (4.55%) 
Reproductive system and breast disorders     
Amenorrhoea  1  0/23 (0.00%)  1/22 (4.55%) 
Dysmenorrhoea  1  5/23 (21.74%)  3/22 (13.64%) 
Genital discharge  1  1/23 (4.35%)  0/22 (0.00%) 
Menorrhagia  1  1/23 (4.35%)  1/22 (4.55%) 
Menstrual discomfort  1  2/23 (8.70%)  0/22 (0.00%) 
Menstruation irregular  1  1/23 (4.35%)  1/22 (4.55%) 
Respiratory, thoracic and mediastinal disorders     
Apnoea  1  1/23 (4.35%)  0/22 (0.00%) 
Asthma  1  0/23 (0.00%)  3/22 (13.64%) 
Atelectasis  1  0/23 (0.00%)  1/22 (4.55%) 
Bronchial secretion retention  1  0/23 (0.00%)  1/22 (4.55%) 
Cough  1  18/23 (78.26%)  16/22 (72.73%) 
Dry throat  1  0/23 (0.00%)  1/22 (4.55%) 
Dysphonia  1  1/23 (4.35%)  2/22 (9.09%) 
Dyspnoea  1  5/23 (21.74%)  3/22 (13.64%) 
Dyspnoea exertional  1  1/23 (4.35%)  1/22 (4.55%) 
Epistaxis  1  2/23 (8.70%)  2/22 (9.09%) 
Increased bronchial secretion  1  0/23 (0.00%)  1/22 (4.55%) 
Increased upper airway secretion  1  1/23 (4.35%)  1/22 (4.55%) 
Nasal congestion  1  9/23 (39.13%)  8/22 (36.36%) 
Nasal discomfort  1  1/23 (4.35%)  1/22 (4.55%) 
Nasal inflammation  1  0/23 (0.00%)  1/22 (4.55%) 
Oropharyngeal pain  1  16/23 (69.57%)  15/22 (68.18%) 
Pharyngeal erythema  1  0/23 (0.00%)  1/22 (4.55%) 
Pharyngeal lesion  1  1/23 (4.35%)  0/22 (0.00%) 
Productive cough  1  1/23 (4.35%)  2/22 (9.09%) 
Rales  1  0/23 (0.00%)  1/22 (4.55%) 
Respiratory disorder  1  1/23 (4.35%)  0/22 (0.00%) 
Respiratory tract congestion  1  2/23 (8.70%)  4/22 (18.18%) 
Rhinitis allergic  1  0/23 (0.00%)  1/22 (4.55%) 
Rhinorrhoea  1  11/23 (47.83%)  9/22 (40.91%) 
Rhonchi  1  0/23 (0.00%)  1/22 (4.55%) 
Sinus congestion  1  0/23 (0.00%)  2/22 (9.09%) 
Sinus disorder  1  1/23 (4.35%)  1/22 (4.55%) 
Sleep apnoea syndrome  1  2/23 (8.70%)  5/22 (22.73%) 
Sneezing  1  6/23 (26.09%)  5/22 (22.73%) 
Throat irritation  1  0/23 (0.00%)  1/22 (4.55%) 
Upper airway resistance syndrome  1  1/23 (4.35%)  0/22 (0.00%) 
Upper respiratory tract congestion  1  0/23 (0.00%)  1/22 (4.55%) 
Wheezing  1  2/23 (8.70%)  2/22 (9.09%) 
Skin and subcutaneous tissue disorders     
Acne  1  3/23 (13.04%)  1/22 (4.55%) 
Acrodermatitis  1  1/23 (4.35%)  0/22 (0.00%) 
Alopecia  1  0/23 (0.00%)  1/22 (4.55%) 
Blister  1  1/23 (4.35%)  0/22 (0.00%) 
Butterfly rash  1  0/23 (0.00%)  1/22 (4.55%) 
Cold sweat  1  2/23 (8.70%)  0/22 (0.00%) 
Dermatitis allergic  1  1/23 (4.35%)  0/22 (0.00%) 
Dermatitis contact  1  0/23 (0.00%)  1/22 (4.55%) 
Drug eruption  1  0/23 (0.00%)  1/22 (4.55%) 
Dry skin  1  6/23 (26.09%)  3/22 (13.64%) 
Ecchymosis  1  1/23 (4.35%)  0/22 (0.00%) 
Eczema  1  1/23 (4.35%)  1/22 (4.55%) 
Erythema  1  2/23 (8.70%)  3/22 (13.64%) 
Excessive granulation tissue  1  0/23 (0.00%)  1/22 (4.55%) 
Ingrowing nail  1  2/23 (8.70%)  1/22 (4.55%) 
Night sweats  1  0/23 (0.00%)  1/22 (4.55%) 
Pain of skin  1  0/23 (0.00%)  1/22 (4.55%) 
Photosensitivity reaction  1  1/23 (4.35%)  0/22 (0.00%) 
Pigmentation disorder  1  0/23 (0.00%)  1/22 (4.55%) 
Pruritus  1  3/23 (13.04%)  3/22 (13.64%) 
Pruritus generalised  1  0/23 (0.00%)  1/22 (4.55%) 
Psoriasis  1  1/23 (4.35%)  0/22 (0.00%) 
Rash  1  12/23 (52.17%)  8/22 (36.36%) 
Rash erythematous  1  1/23 (4.35%)  1/22 (4.55%) 
Rash generalised  1  0/23 (0.00%)  1/22 (4.55%) 
Rash macular  1  1/23 (4.35%)  1/22 (4.55%) 
Rash maculo-papular  1  1/23 (4.35%)  0/22 (0.00%) 
Rash papular  1  1/23 (4.35%)  2/22 (9.09%) 
Rash pruritic  1  2/23 (8.70%)  1/22 (4.55%) 
Scab  1  1/23 (4.35%)  0/22 (0.00%) 
Scar  1  0/23 (0.00%)  1/22 (4.55%) 
Skin discolouration  1  0/23 (0.00%)  1/22 (4.55%) 
Skin erosion  1  1/23 (4.35%)  0/22 (0.00%) 
Skin exfoliation  1  0/23 (0.00%)  1/22 (4.55%) 
Skin induration  1  0/23 (0.00%)  1/22 (4.55%) 
Skin inflammation  1  0/23 (0.00%)  1/22 (4.55%) 
Skin lesion  1  4/23 (17.39%)  3/22 (13.64%) 
Skin reaction  1  1/23 (4.35%)  0/22 (0.00%) 
Swelling face  1  1/23 (4.35%)  1/22 (4.55%) 
Urticaria  1  2/23 (8.70%)  2/22 (9.09%) 
Surgical and medical procedures     
Tooth extraction  1  2/23 (8.70%)  2/22 (9.09%) 
Tooth repair  1  0/23 (0.00%)  1/22 (4.55%) 
Vascular disorders     
Flushing  1  3/23 (13.04%)  5/22 (22.73%) 
Hypertension  1  2/23 (8.70%)  1/22 (4.55%) 
Hypotension  1  0/23 (0.00%)  1/22 (4.55%) 
Orthostatic hypotension  1  1/23 (4.35%)  0/22 (0.00%) 
Pallor  1  1/23 (4.35%)  0/22 (0.00%) 
Poor venous access  1  4/23 (17.39%)  2/22 (9.09%) 
Vein disorder  1  1/23 (4.35%)  1/22 (4.55%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.1
Rare disease with limited sample size, lack of control group.FVC calculations less reliable for patients whose height is below the 3rdpercent of general population.Height term used to calculate FVC may be influenced by joint contractures and posture.
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.
In multi-site studies, PI can publish after Genzyme publishes or 18 months after study completion. PI gives Genzyme a draft 60 days before publication. Genzyme can ask that confidential information be removed, and can defer publication another 60 days upon notifying PI that it will file a patent application on inventions contained in the draft.
Results Point of Contact
Name/Title: Genzyme Medical Information
Organization: Genzyme Corporation
Phone: 800-745-4447
Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00146770     History of Changes
Other Study ID Numbers: ALID-006-01
First Submitted: September 2, 2005
First Posted: September 7, 2005
Results First Submitted: January 7, 2009
Results First Posted: June 16, 2009
Last Update Posted: April 3, 2015