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A Placebo-Controlled Study of Safety and Effectiveness of Myozyme (Alglucosidase Alfa) in Patients With Late-Onset Pompe 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: NCT00158600
Recruitment Status : Completed
First Posted : September 12, 2005
Results First Posted : July 23, 2010
Last Update Posted : April 28, 2015
Sponsor:
Information provided by:
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Pompe Disease (Late-onset)
Glycogen Storage Disease Type II (GSD-II)
Acid Maltase Deficiency Disease
Glycogenosis 2
Interventions Biological: alglucosidase alfa
Drug: Placebo
Enrollment 90
Recruitment Details  
Pre-assignment Details One hundred patients screened and 90 enrolled.
Arm/Group Title Alglucosidase Alfa Placebo
Hide Arm/Group Description Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks. Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.
Period Title: Overall Study
Started 60 30
Completed 55 26
Not Completed 5 4
Reason Not Completed
unable to commit time to study             0             1
Adverse Event             2             1
Death             1             0
Withdrawal by Subject             2             2
Arm/Group Title Alglucosidase Alfa Placebo Total
Hide Arm/Group Description Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks. Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks. Total of all reporting groups
Overall Number of Baseline Participants 60 30 90
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 60 participants 30 participants 90 participants
45.3  (12.37) 42.6  (11.63) 44.4  (12.14)
[1]
Measure Description: Age at First Infusion
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 60 participants 30 participants 90 participants
Female
26
  43.3%
19
  63.3%
45
  50.0%
Male
34
  56.7%
11
  36.7%
45
  50.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 60 participants 30 participants 90 participants
Hispanic 1 1 2
Asian 1 1 2
Black or African American 0 0 0
White 57 27 84
Unknown or not reported 1 1 2
1.Primary Outcome
Title Summary of Patients Reporting Treatment-Emergent Adverse Events
Hide Description Overall safety summary of patients experiencing Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, and Infusion Associated Reactions (IARs). Summary is based on Treatment-emergent AEs (TEAEs), defined as AEs that occurred following the initiation of study treatment, i.e., alglucosidase alfa or placebo.
Time Frame weeks 0-78
Hide Outcome Measure Data
Hide Analysis Population Description

All patients who received any amount of study treatment comprise the safety population. Patients were considered, for safety analysis, to be in the treatment group of the treatment they actually received.

Missing or invalid safety or resource utilization data were not replaced.

Arm/Group Title Alglucosidase Alfa Placebo
Hide Arm/Group Description:
Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.
Overall Number of Participants Analyzed 60 30
Measure Type: Number
Unit of Measure: participants
Patients with Any AEs 60 30
Patients with Treatment-Related AEs 32 17
Patients with Infusion-Associated Reactions 17 7
Patients with SAEs 13 6
Patients with Severe AEs 14 10
Patients who Discontinued Due to AEs (incl death) 3 1
Patients who Died 1 0
2.Primary Outcome
Title Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline
Hide Description Mean distance walked gives an indication of functional endurance. The greater the distance, the greater the endurance. Mean values of distance walked in a six-minute walk test are offered for baseline, week 78 (or last available observation), and the mean change from baseline (at week 78 or last available post-baseline observation).
Time Frame weeks 0, 78
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) population. Last observation carried forward. The last available distance walked for one patient was the Baseline visit; therefore, this patient was excluded from the change from baseline calculation.
Arm/Group Title Alglucosidase Alfa Placebo
Hide Arm/Group Description:
Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.
Overall Number of Participants Analyzed 60 30
Mean (Standard Deviation)
Unit of Measure: meters
Distance Walked at Baseline 332.20  (126.69) 317.93  (132.29)
Distance Walked at Last Available Observation 357.85  (141.32) 313.07  (144.69)
Change at Last Available Observation from Baseline 26.08  (64.41) -4.87  (45.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alglucosidase Alfa, Placebo
Comments The difference between alglucosidase alfa and placebo treatment groups in change in distance walked from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0347
Comments The threshold for determining statistical significance is 0.05. A fixed testing sequence procedure was used to preserve an overall error rate of 5% for the co-primary efficacy endpoints by linking the test of FVC to the result of 6MWT.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 28.12
Confidence Interval 95%
2.07 to 54.17
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percent of Predicted Forced Vital Capacity (FVC)
Hide Description Forced vital capacity is a standard pulmonary function test used to quantify respiratory muscle weakness. Forced vital capacity (FVC) is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%.
Time Frame weeks 0, 78
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Last observation carried forward.
Arm/Group Title Alglucosidase Alfa Placebo
Hide Arm/Group Description:
Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.
Overall Number of Participants Analyzed 60 30
Mean (Standard Deviation)
Unit of Measure: percent predicted FVC
Baseline (week 0) 55.43  (14.44) 53.00  (15.66)
Week 78 (or last observation) 56.71  (16.30) 50.70  (14.88)
Change at Week 78 from Baseline 1.25  (5.55) -2.30  (4.33)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alglucosidase Alfa, Placebo
Comments The difference between alglucosidase alfa and placebo treatment groups in change in % predicted FVC from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0055
Comments The threshold for determining statistical significance is 0.05. A fixed testing sequence procedure was used to preserve an overall error rate of 5% for the co-primary efficacy endpoints by linking the test of FVC to the result of 6MWT.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 3.40
Confidence Interval 95%
1.03 to 5.77
Estimation Comments [Not Specified]
4.Primary Outcome
Title Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)
Hide Description Area under the plasma concentration versus time curve from time zero (pre-dose) to 16 hours after the end of infusion. Blood sample time points were 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes.
Time Frame weeks 0, 12 and 52
Hide Outcome Measure Data
Hide Analysis Population Description
The subgroup of patients for whom pharmacokinetic samples were obtained was based on those study sites that could accommodate pharmacokinetic sampling needs.
Arm/Group Title Alglucosidase Alfa
Hide Arm/Group Description:
Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Overall Number of Participants Analyzed 32
Mean (Standard Deviation)
Unit of Measure: ug*h/mL
Week 0 2672.47  (1139.85)
Week 12 2386.76  (555.09)
Week 52 2699.28  (999.97)
Pooled 2586.17  (933.28)
5.Primary Outcome
Title Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)
Hide Description Maximum plasma concentration observed in blood samples taken at the following time points: 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes.
Time Frame weeks 0, 12, 52
Hide Outcome Measure Data
Hide Analysis Population Description
The subgroup of patients for whom pharmacokinetic samples were obtained was based on those study sites that could accommodate pharmacokinetic sampling needs.
Arm/Group Title Alglucosidase Alfa
Hide Arm/Group Description:
Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Overall Number of Participants Analyzed 32
Mean (Standard Deviation)
Unit of Measure: ng/mL
Week 0 385237  (105585)
Week 12 349269  (78620)
Week 52 369744  (88203)
Pooled 368083  (91721)
6.Primary Outcome
Title Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)
Hide Description Time to maximum plasma concentration observed in blood samples taken at the following time points: 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes.
Time Frame weeks 0, 12, 52
Hide Outcome Measure Data
Hide Analysis Population Description
The subgroup of patients for whom pharmacokinetic samples were obtained was based on those study sites that could accommodate pharmacokinetic sampling needs.
Arm/Group Title Alglucosidase Alfa
Hide Arm/Group Description:
Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Overall Number of Participants Analyzed 32
Mean (Standard Deviation)
Unit of Measure: hours
Week 0 3.62  (0.33)
Week 12 3.62  (0.28)
Week 52 3.64  (0.31)
Pooled 3.63  (0.30)
7.Secondary Outcome
Title Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)
Hide Description Quantitative muscle testing (QMT) is a standardized system to measure muscle force production during maximal voluntary isometric contraction. QMT data were collected directly from sensors into laptop computers. Predicted normal values for QMT are based on a formula using sex, age and body mass index of a person, and is an estimate of healthy muscle force. Percent of predicted QMT = (observed value)/(predicted value) * 100%. The QMT Leg Score is the average of the bilateral means for percent predicted knee flexors and extensors. A value of 100% indicates 'normal' muscle strength.
Time Frame weeks 0, 78
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Last observation carried forward.
Arm/Group Title Alglucosidase Alfa Placebo
Hide Arm/Group Description:
Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.
Overall Number of Participants Analyzed 60 30
Mean (Standard Deviation)
Unit of Measure: percent predicted QMT
Baseline (week 0) 37.69  (18.88) 32.49  (18.24)
Week 78 (or last available observation) 39.05  (21.83) 30.40  (20.54)
Change at Week 78 from Baseline 1.22  (9.88) -2.08  (5.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alglucosidase Alfa, Placebo
Comments The difference between alglucosidase alfa and placebo treatment groups in change in QMT from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1093
Comments The threshold for determining statistical significance is 0.05. No adjustment for multiple comparison was made for secondary efficacy endpoints.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value 3.18
Confidence Interval 95%
-0.73 to 7.08
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey
Hide Description The Medical Outcomes Study Short Form (MOS SF)-36 questionnaire consists of 36 items grouped into 8 domains designed to assess generic health-related quality of life in healthy and ill adult populations. Physical Component Scores (PCS) report the four domains of physical functioning, role-physical, bodily pain, and general health. Higher scores are associated with better quality of life. All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible. The PCS scores are reported.
Time Frame weeks 0, 78
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Last observation carried forward.
Arm/Group Title Alglucosidase Alfa Placebo
Hide Arm/Group Description:
Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks.
Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks.
Overall Number of Participants Analyzed 60 30
Mean (Standard Deviation)
Unit of Measure: Units on a scale
PCS at Baseline (week 0) 34.33  (8.93) 34.91  (7.26)
PCS at Week 78 (or last available observation) 35.11  (9.84) 36.47  (9.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Alglucosidase Alfa, Placebo
Comments The difference between alglucosidase alfa and placebo treatment groups in change in PCS from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8333
Comments The threshold for determining statistical significance is 0.05. No adjustment for multiple comparison was made for secondary efficacy endpoints.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference
Estimated Value -0.37
Confidence Interval 95%
-3.83 to 3.09
Estimation Comments [Not Specified]
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. Events are listed independent of relationship to treatment reported.
 
Arm/Group Title Alglucosidase Alfa Placebo Overall
Hide Arm/Group Description Intravenous (IV) infusions of alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow) for 78 weeks. Intravenous (IV) infusions of placebo every other week (qow) for 78 weeks. [Not Specified]
All-Cause Mortality
Alglucosidase Alfa Placebo Overall
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Alglucosidase Alfa Placebo Overall
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   13/60 (21.67%)   6/30 (20.00%)   19/90 (21.11%) 
Cardiac disorders       
Coronary artery disease  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Supraventricular tachycardia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Gastrointestinal disorders       
Abdominal pain  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Abdominal pain upper  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
General disorders       
Chest discomfort  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Non-cardiac chest pain  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Immune system disorders       
Hypersensitivity  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Infections and infestations       
Diverticulitis  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Gastroenteritis  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Pneumonia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Injury, poisoning and procedural complications       
Fall  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Humerus fracture  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Metabolism and nutrition disorders       
Dehydration  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Musculoskeletal and connective tissue disorders       
Flank pain  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Intervertebral disc protrusion  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Nervous system disorders       
Brain stem ischaemia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Headache  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Respiratory, thoracic and mediastinal disorders       
Lung disorder  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Throat tightness  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Skin and subcutaneous tissue disorders       
Angioneurotic oedema  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Septal panniculitis  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Vascular disorders       
Aneurysm  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Alglucosidase Alfa Placebo Overall
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   60/60 (100.00%)   30/30 (100.00%)   90/90 (100.00%) 
Blood and lymphatic system disorders       
Anaemia  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Lymphadenopathy  1  5/60 (8.33%)  0/30 (0.00%)  5/90 (5.56%) 
Macrocytosis  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Normochromic normocytic anaemia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Cardiac disorders       
Angina pectoris  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Bundle branch block left  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Bundle branch block right  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Coronary artery disease  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Palpitations  1  3/60 (5.00%)  1/30 (3.33%)  4/90 (4.44%) 
Sinus tachycardia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Tachycardia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Tricuspid valve incompetence  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Ear and labyrinth disorders       
Auricular swelling  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Ear congestion  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Ear discomfort  1  4/60 (6.67%)  1/30 (3.33%)  5/90 (5.56%) 
Ear pain  1  3/60 (5.00%)  1/30 (3.33%)  4/90 (4.44%) 
Hypoacusis  1  20/60 (33.33%)  7/30 (23.33%)  27/90 (30.00%) 
Presbyacusis  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Tinnitus  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Tympanic membrane disorder  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Tympanic membrane scarring  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Vertigo  1  4/60 (6.67%)  0/30 (0.00%)  4/90 (4.44%) 
Eye disorders       
Altered visual depth perception  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Asthenopia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Cataract  1  4/60 (6.67%)  2/30 (6.67%)  6/90 (6.67%) 
Conjunctivitis  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Diplopia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Dry eye  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Eye irritation  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Eye pruritus  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Lacrimation increased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Photophobia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Vision blurred  1  3/60 (5.00%)  0/30 (0.00%)  3/90 (3.33%) 
Visual disturbance  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Vitreous floaters  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Gastrointestinal disorders       
Abdominal discomfort  1  2/60 (3.33%)  2/30 (6.67%)  4/90 (4.44%) 
Abdominal distension  1  1/60 (1.67%)  2/30 (6.67%)  3/90 (3.33%) 
Abdominal mass  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Abdominal pain  1  4/60 (6.67%)  3/30 (10.00%)  7/90 (7.78%) 
Abdominal pain lower  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Abdominal pain upper  1  6/60 (10.00%)  2/30 (6.67%)  8/90 (8.89%) 
Constipation  1  6/60 (10.00%)  0/30 (0.00%)  6/90 (6.67%) 
Dental caries  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Diarrhoea  1  18/60 (30.00%)  13/30 (43.33%)  31/90 (34.44%) 
Diverticulum  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Dry mouth  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Dyspepsia  1  5/60 (8.33%)  0/30 (0.00%)  5/90 (5.56%) 
Dysphagia  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Epigastric discomfort  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Flatulence  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Food poisoning  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Gastrointestinal disorder  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Gastrooesophageal reflux disease  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Glossodynia  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Haematochezia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Hiatus hernia  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Inguinal hernia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Lip swelling  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Nausea  1  11/60 (18.33%)  10/30 (33.33%)  21/90 (23.33%) 
Oesophageal pain  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Oral mucosal blistering  1  0/60 (0.00%)  2/30 (6.67%)  2/90 (2.22%) 
Oral pruritus  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Paraesthesia oral  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Retching  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Stomach discomfort  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Swollen tongue  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Toothache  1  1/60 (1.67%)  4/30 (13.33%)  5/90 (5.56%) 
Vomiting  1  13/60 (21.67%)  3/30 (10.00%)  16/90 (17.78%) 
General disorders       
Application site vesicles  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Asthenia  1  3/60 (5.00%)  4/30 (13.33%)  7/90 (7.78%) 
Axillary pain  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Catheter related complication  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Catheter site pain  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Catheter site related reaction  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Chest discomfort  1  6/60 (10.00%)  1/30 (3.33%)  7/90 (7.78%) 
Chest pain  1  4/60 (6.67%)  1/30 (3.33%)  5/90 (5.56%) 
Chills  1  3/60 (5.00%)  1/30 (3.33%)  4/90 (4.44%) 
Fatigue  1  7/60 (11.67%)  6/30 (20.00%)  13/90 (14.44%) 
Feeling abnormal  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Feeling cold  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Feeling hot  1  3/60 (5.00%)  2/30 (6.67%)  5/90 (5.56%) 
Feeling hot and cold  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Gait disturbance  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Hangover  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Influenza like illness  1  2/60 (3.33%)  4/30 (13.33%)  6/90 (6.67%) 
Infusion site bruising  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Infusion site pain  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Infusion site paraesthesia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Infusion site reaction  1  5/60 (8.33%)  0/30 (0.00%)  5/90 (5.56%) 
Injection site phlebitis  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Local swelling  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Malaise  1  3/60 (5.00%)  0/30 (0.00%)  3/90 (3.33%) 
Non-cardiac chest pain  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Oedema peripheral  1  10/60 (16.67%)  3/30 (10.00%)  13/90 (14.44%) 
Pain  1  5/60 (8.33%)  1/30 (3.33%)  6/90 (6.67%) 
Pitting oedema  1  2/60 (3.33%)  2/30 (6.67%)  4/90 (4.44%) 
Puncture site haemorrhage  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Pyrexia  1  8/60 (13.33%)  8/30 (26.67%)  16/90 (17.78%) 
Thirst  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Vessel puncture site haematoma  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Immune system disorders       
Hypersensitivity  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Infections and infestations       
Bronchitis  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Bronchopneumonia  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Cellulitis  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Cystitis  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Dermatophytosis  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Eye infection  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Folliculitis  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Fungal infection  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Fungal skin infection  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Gastroenteritis  1  5/60 (8.33%)  1/30 (3.33%)  6/90 (6.67%) 
Gastroenteritis viral  1  3/60 (5.00%)  3/30 (10.00%)  6/90 (6.67%) 
Gastrointestinal infection  1  0/60 (0.00%)  2/30 (6.67%)  2/90 (2.22%) 
Genital infection  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Gingival infection  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Herpes simplex  1  4/60 (6.67%)  3/30 (10.00%)  7/90 (7.78%) 
Herpes virus infection  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Influenza  1  5/60 (8.33%)  7/30 (23.33%)  12/90 (13.33%) 
Kidney infection  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Laryngitis  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Localised infection  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Mucosal infection  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Nasopharyngitis  1  25/60 (41.67%)  16/30 (53.33%)  41/90 (45.56%) 
Otitis media  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Postoperative wound infection  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Rash pustular  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Respiratory tract infection  1  3/60 (5.00%)  0/30 (0.00%)  3/90 (3.33%) 
Rhinitis  1  0/60 (0.00%)  2/30 (6.67%)  2/90 (2.22%) 
Sinusitis  1  4/60 (6.67%)  4/30 (13.33%)  8/90 (8.89%) 
Tinea pedis  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Tonsillitis  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Tooth infection  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Upper respiratory tract infection  1  11/60 (18.33%)  3/30 (10.00%)  14/90 (15.56%) 
Urinary tract infection  1  5/60 (8.33%)  4/30 (13.33%)  9/90 (10.00%) 
Vaginal infection  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Viral infection  1  2/60 (3.33%)  2/30 (6.67%)  4/90 (4.44%) 
Vulvovaginal mycotic infection  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Wound infection  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Injury, poisoning and procedural complications       
Accident  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Animal bite  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Arthropod bite  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Arthropod sting  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Back injury  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Contusion  1  4/60 (6.67%)  6/30 (20.00%)  10/90 (11.11%) 
Excoriation  1  0/60 (0.00%)  3/30 (10.00%)  3/90 (3.33%) 
Fall  1  39/60 (65.00%)  20/30 (66.67%)  59/90 (65.56%) 
Femur fracture  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Foot fracture  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Humerus fracture  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Injury  1  4/60 (6.67%)  1/30 (3.33%)  5/90 (5.56%) 
Injury corneal  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Joint dislocation  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Joint sprain  1  1/60 (1.67%)  2/30 (6.67%)  3/90 (3.33%) 
Laceration  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Ligament injury  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Limb crushing injury  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Limb injury  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Muscle strain  1  4/60 (6.67%)  4/30 (13.33%)  8/90 (8.89%) 
Periorbital haematoma  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Procedural pain  1  9/60 (15.00%)  3/30 (10.00%)  12/90 (13.33%) 
Repetitive strain injury  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Rib fracture  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Road traffic accident  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Skeletal injury  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Skin laceration  1  4/60 (6.67%)  1/30 (3.33%)  5/90 (5.56%) 
Tendon injury  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Thermal burn  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Tooth fracture  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Traumatic ulcer  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Vaccination complication  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Wound  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Investigations       
Alanine aminotransferase increased  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Aspartate aminotransferase increased  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Blood alkaline phosphatase increased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Blood creatine phosphokinase MB increased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Blood folate decreased  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Blood glucose increased  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Blood parathyroid hormone increased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Blood pressure increased  1  3/60 (5.00%)  1/30 (3.33%)  4/90 (4.44%) 
Blood thyroid stimulating hormone increased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Blood uric acid increased  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Blood urine present  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Carbon dioxide increased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Electrocardiogram QT corrected interval prolonged  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Eosinophil count increased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Forced expiratory volume decreased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Glucose urine present  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Heart rate irregular  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
International normalised ratio decreased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Lymph node palpable  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Neutrophil count increased  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Oxygen saturation decreased  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Protein total increased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Protein urine present  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Specific gravity urine decreased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Urine ketone body present  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Vitamin D decreased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Weight decreased  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Weight increased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
White blood cell count increased  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
White blood cells urine positive  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Metabolism and nutrition disorders       
Decreased appetite  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Diabetes mellitus non-insulin-dependent  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Hyperglycaemia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Hypernatraemia  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Hypertriglyceridaemia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Hypokalaemia  1  3/60 (5.00%)  0/30 (0.00%)  3/90 (3.33%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  18/60 (30.00%)  9/30 (30.00%)  27/90 (30.00%) 
Back pain  1  14/60 (23.33%)  7/30 (23.33%)  21/90 (23.33%) 
Bone pain  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Bursitis  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Buttock pain  1  3/60 (5.00%)  1/30 (3.33%)  4/90 (4.44%) 
Costochondritis  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Exostosis  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Flank pain  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Foot deformity  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Groin pain  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Joint range of motion decreased  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Joint swelling  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Muscle atrophy  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Muscle contracture  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Muscle spasms  1  14/60 (23.33%)  6/30 (20.00%)  20/90 (22.22%) 
Muscle tightness  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Muscle twitching  1  5/60 (8.33%)  1/30 (3.33%)  6/90 (6.67%) 
Muscular weakness  1  6/60 (10.00%)  3/30 (10.00%)  9/90 (10.00%) 
Musculoskeletal chest pain  1  5/60 (8.33%)  1/30 (3.33%)  6/90 (6.67%) 
Musculoskeletal discomfort  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Musculoskeletal disorder  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Musculoskeletal pain  1  8/60 (13.33%)  2/30 (6.67%)  10/90 (11.11%) 
Musculoskeletal stiffness  1  8/60 (13.33%)  1/30 (3.33%)  9/90 (10.00%) 
Myalgia  1  12/60 (20.00%)  5/30 (16.67%)  17/90 (18.89%) 
Neck pain  1  7/60 (11.67%)  5/30 (16.67%)  12/90 (13.33%) 
Nose deformity  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Osteopenia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Osteoporosis  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Pain in extremity  1  15/60 (25.00%)  7/30 (23.33%)  22/90 (24.44%) 
Plantar fasciitis  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Scoliosis  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Sensation of heaviness  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Temporomandibular joint syndrome  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Tendon pain  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Tendonitis  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Tenosynovitis stenosans  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Melanocytic naevus  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Nervous system disorders       
Areflexia  1  3/60 (5.00%)  2/30 (6.67%)  5/90 (5.56%) 
Balance disorder  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Burning sensation  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Carpal tunnel syndrome  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Disturbance in attention  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Dizziness  1  14/60 (23.33%)  6/30 (20.00%)  20/90 (22.22%) 
Dizziness postural  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Dysgeusia  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Facial palsy  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Head discomfort  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Headache  1  24/60 (40.00%)  15/30 (50.00%)  39/90 (43.33%) 
Hyperreflexia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Hypoaesthesia  1  2/60 (3.33%)  2/30 (6.67%)  4/90 (4.44%) 
Hyporeflexia  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Intercostal neuralgia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Intracranial hypotension  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Lethargy  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Loss of consciousness  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Migraine  1  3/60 (5.00%)  1/30 (3.33%)  4/90 (4.44%) 
Nerve compression  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Paraesthesia  1  6/60 (10.00%)  4/30 (13.33%)  10/90 (11.11%) 
Poor quality sleep  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Sinus headache  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Somnolence  1  3/60 (5.00%)  0/30 (0.00%)  3/90 (3.33%) 
Syncope vasovagal  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Tremor  1  4/60 (6.67%)  0/30 (0.00%)  4/90 (4.44%) 
Psychiatric disorders       
Abnormal dreams  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Anxiety  1  2/60 (3.33%)  3/30 (10.00%)  5/90 (5.56%) 
Depression  1  1/60 (1.67%)  2/30 (6.67%)  3/90 (3.33%) 
Insomnia  1  6/60 (10.00%)  2/30 (6.67%)  8/90 (8.89%) 
Panic attack  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Stress  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Renal and urinary disorders       
Haematuria  1  3/60 (5.00%)  1/30 (3.33%)  4/90 (4.44%) 
Leukocyturia  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Nephrolithiasis  1  3/60 (5.00%)  0/30 (0.00%)  3/90 (3.33%) 
Pollakiuria  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Proteinuria  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Pyuria  1  1/60 (1.67%)  2/30 (6.67%)  3/90 (3.33%) 
Urinary incontinence  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Urine flow decreased  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Urine odour abnormal  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Reproductive system and breast disorders       
Breast pain  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Breast swelling  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Breast tenderness  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Dysmenorrhoea  1  0/60 (0.00%)  2/30 (6.67%)  2/90 (2.22%) 
Fibrocystic breast disease  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Genital pruritus female  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Menstrual discomfort  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Menstruation irregular  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Scrotal cyst  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Vaginal haemorrhage  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Respiratory, thoracic and mediastinal disorders       
Asthma  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Bronchospasm  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Cough  1  6/60 (10.00%)  5/30 (16.67%)  11/90 (12.22%) 
Dyspnoea  1  7/60 (11.67%)  4/30 (13.33%)  11/90 (12.22%) 
Dyspnoea exertional  1  4/60 (6.67%)  0/30 (0.00%)  4/90 (4.44%) 
Epistaxis  1  3/60 (5.00%)  0/30 (0.00%)  3/90 (3.33%) 
Increased bronchial secretion  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Lung disorder  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Lung infiltration  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Nasal congestion  1  2/60 (3.33%)  2/30 (6.67%)  4/90 (4.44%) 
Paranasal sinus hypersecretion  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Pharyngolaryngeal pain  1  12/60 (20.00%)  5/30 (16.67%)  17/90 (18.89%) 
Postnasal drip  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Rales  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Respiratory distress  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Respiratory failure  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Respiratory tract congestion  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Rhinorrhoea  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Sinus congestion  1  2/60 (3.33%)  3/30 (10.00%)  5/90 (5.56%) 
Sleep apnoea syndrome  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Sneezing  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Throat irritation  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Throat tightness  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Wheezing  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Skin and subcutaneous tissue disorders       
Acne  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Blister  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Cold sweat  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Decubitus ulcer  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Dermatitis contact  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Drug eruption  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Ecchymosis  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Eczema  1  0/60 (0.00%)  2/30 (6.67%)  2/90 (2.22%) 
Erythema  1  3/60 (5.00%)  1/30 (3.33%)  4/90 (4.44%) 
Heat rash  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Hyperhidrosis  1  5/60 (8.33%)  0/30 (0.00%)  5/90 (5.56%) 
Ingrowing nail  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Photosensitivity reaction  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Pruritus  1  6/60 (10.00%)  1/30 (3.33%)  7/90 (7.78%) 
Rash  1  6/60 (10.00%)  3/30 (10.00%)  9/90 (10.00%) 
Rash macular  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Rash maculo-papular  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Rash papular  1  3/60 (5.00%)  0/30 (0.00%)  3/90 (3.33%) 
Rash pruritic  1  4/60 (6.67%)  1/30 (3.33%)  5/90 (5.56%) 
Skin burning sensation  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Skin lesion  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Skin nodule  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Skin odour abnormal  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Skin warm  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Subcutaneous nodule  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Telangiectasia  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Urticaria  1  6/60 (10.00%)  0/30 (0.00%)  6/90 (6.67%) 
Vascular disorders       
Aneurysm  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Diastolic hypotension  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Flushing  1  3/60 (5.00%)  2/30 (6.67%)  5/90 (5.56%) 
Haematoma  1  2/60 (3.33%)  0/30 (0.00%)  2/90 (2.22%) 
Hot flush  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Hypertension  1  3/60 (5.00%)  1/30 (3.33%)  4/90 (4.44%) 
Hypotension  1  2/60 (3.33%)  1/30 (3.33%)  3/90 (3.33%) 
Phlebitis  1  0/60 (0.00%)  1/30 (3.33%)  1/90 (1.11%) 
Raynaud's phenomenon  1  1/60 (1.67%)  1/30 (3.33%)  2/90 (2.22%) 
Vasoconstriction  1  1/60 (1.67%)  0/30 (0.00%)  1/90 (1.11%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 9.1
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
Layout table for Results Point of Contact information
Name/Title: Genzyme Medical Information
Organization: Genzyme Corporation
Phone: 800-745-4447
Layout table for additonal information
Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT00158600     History of Changes
Other Study ID Numbers: AGLU02704
2005-002759-42 ( EudraCT Number )
First Submitted: September 8, 2005
First Posted: September 12, 2005
Results First Submitted: June 24, 2010
Results First Posted: July 23, 2010
Last Update Posted: April 28, 2015