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Iduronate-2-sulfatase Enzyme Replacement Therapy in Mucopolysaccharidosis II (MPS II)

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ClinicalTrials.gov Identifier: NCT00069641
Recruitment Status : Completed
First Posted : October 1, 2003
Results First Posted : May 13, 2015
Last Update Posted : May 13, 2015
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Mucopolysaccharidosis II
Interventions Biological: Iduronate-2-sulfatase enzyme replacement therapy
Biological: iduronate-2-sulfatase enzyme replacement therapy
Biological: Placebo
Enrollment 96
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Idursulfase Weekly (0.5 mg/kg) Idursulfase Every Other Week (EOW) (0.5 mg/kg) Placebo
Hide Arm/Group Description Idursulfase 0.5 milligram per kilogram (mg/kg) administered once-weekly by intravenous infusion for one year (52 infusions). Idursulfase 0.5 mg/kg administered every other week by intravenous infusion for one year (26 infusions) along with placebo matching to idursulfase every other week (alternating with idursulfase) by intravenous infusion for one year (26 infusions). Placebo matching to idursulfase administered once-weekly by intravenous infusion for one year (52 infusions).
Period Title: Overall Study
Started 32 32 32
Completed 31 32 31
Not Completed 1 0 1
Reason Not Completed
Death             1             0             1
Arm/Group Title Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo Total
Hide Arm/Group Description Idursulfase 0.5 mg/kg administered once-weekly by intravenous infusion for one year (52 infusions). Idursulfase 0.5 mg/kg administered every other week by intravenous infusion for one year (26 infusions) along with placebo matching to idursulfase every other week (alternating with idursulfase) by intravenous infusion for one year (26 infusions). Placebo matching to idursulfase administered once-weekly by intravenous infusion for one year (52 infusions). Total of all reporting groups
Overall Number of Baseline Participants 32 32 32 96
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 32 participants 32 participants 96 participants
15.14  (6.293) 14.40  (7.019) 13.12  (6.908) 14.22  (6.729)
[1]
Measure Description: Age at randomization.
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 32 participants 32 participants 32 participants 96 participants
5 to 11 years 14 14 15 43
12 to 18 years 10 9 10 29
19 to 25 years 7 7 5 19
greater than equal to (>=) 26 years 1 2 2 5
[1]
Measure Description:

Age at randomization. The participant who was less than (<) 5 years old was considered for randomization to be in 5 to 11 years category.

Participants who were greater than (>) 25 years old were considered for randomization to be in 19 to 25 years category.

Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 32 participants 32 participants 96 participants
Female
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Male
32
 100.0%
32
 100.0%
32
 100.0%
96
 100.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 32 participants 32 participants 32 participants 96 participants
North America 11 11 12 34
South America 7 7 7 21
Europe 14 14 13 41
1.Primary Outcome
Title Ranked Adjusted 2-Component Composite Variable Score Based on Change From Baseline to Week 53
Hide Description The 2-component composite variable consists of the sum of the ranked changes from baseline to Week 53 for percent predicted Forced Vital Capacity (FVC) and 6-Minute Walking Test (6MWT) total distance walked. For the 2 treatment groups being compared, ranking occurred within the comparison treatment groups combined (idursulfase weekly and placebo treatment groups). These comparison groups were pooled and ranked for each component separately. Within each component (% predicted FVC, 6MWT), the change from baseline was then ranked. The lowest change value was assigned a rank of 1, the next lowest a rank of 2, etc. The composite score for each participant was the sum of the 2 ranked scores corresponding to the 2 individual components (% predicted FVC and 6MWT) for each participant. Thus, the greater the composite score (greater the sum of the ranks of the changes from baseline, where the lowest change was ranked as 1), the greater the improvement.
Time Frame Baseline, Week 53
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population, Only participants receiving “Idursulfase Weekly” or “Placebo” were to be analyzed for this outcome.
Arm/Group Title Idursulfase Weekly (0.5 mg/kg) Placebo
Hide Arm/Group Description:
Idursulfase 0.5 mg/kg administered once-weekly by intravenous infusion for one year (52 infusions).
Placebo matching to idursulfase administered once-weekly by intravenous infusion for one year (52 infusions).
Overall Number of Participants Analyzed 32 32
Mean (Standard Error)
Unit of Measure: sum of the ranked scores
69.81  (7.03) 50.86  (8.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Idursulfase Weekly (0.5 mg/kg), Placebo
Comments p-value for treatment difference based on Analysis of covariance (ANCOVA) model containing treatment, region, baseline participant age, and baseline disease score.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0049
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 18.96
Confidence Interval (2-Sided) 95%
5.99 to 31.93
Parameter Dispersion
Type: Standard Error of the mean
Value: 6.47
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Mean Global Joint Range of Motion (JROM) Score at Week 53
Hide Description Change was calculated at Week 53 from baseline. Global JROM (% of normal range of motion) is the average of 11 ratios multiplied by 100. Ratios are Left/Right means of passive range of motion in Shoulder (Flexion/Extension, Abduction, Internal/External Rotation), Elbow (Flexion/Extension), Wrist (Flexion/Extension), Index Finger (Flexion/Extension [Combined Metacarpophalangeal joint (MCP), Proximal interphalangeal joint (PIP), Distal interphalangeal joint (DIP) motion]), Hip (Flexion/Extension, Abduction, Internal/External Rotation), Knee (Flexion/Extension), and Ankle (Dorsiflexion) divided by the normal range (American Academy of Orthopedic Surgeons and American Medical Association).
Time Frame Baseline, Week 53
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, number of participants analyzed = participants who were evaluable for this measure.
Arm/Group Title Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo
Hide Arm/Group Description:
Idursulfase 0.5 mg/kg administered once-weekly by intravenous infusion for one year (52 infusions).
Idursulfase 0.5 mg/kg administered every other week by intravenous infusion for one year (26 infusions) along with placebo matching to idursulfase every other week (alternating with idursulfase) by intravenous infusion for one year (26 infusions).
Placebo matching to idursulfase administered once-weekly by intravenous infusion for one year (52 infusions).
Overall Number of Participants Analyzed 31 32 31
Mean (Standard Error)
Unit of Measure: percentage of normal range of motion
Baseline 66.86  (1.85) 67.36  (1.43) 67.70  (1.59)
Change at Week 53 0.89  (0.87) -0.61  (0.94) 0.70  (1.10)
3.Secondary Outcome
Title Mean Combined Liver and Spleen Volume at Baseline
Hide Description Liver and Spleen volume was determined by Magnetic Resonance Imaging (MRI).
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, number of participants analyzed = participants who were evaluable for this measure.
Arm/Group Title Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo
Hide Arm/Group Description:
Idursulfase 0.5 mg/kg administered once-weekly by intravenous infusion for one year (52 infusions).
Idursulfase 0.5 mg/kg administered every other week by intravenous infusion for one year (26 infusions) along with placebo matching to idursulfase every other week (alternating with idursulfase) by intravenous infusion for one year (26 infusions).
Placebo matching to idursulfase administered once-weekly by intravenous infusion for one year (52 infusions).
Overall Number of Participants Analyzed 31 29 30
Mean (Standard Error)
Unit of Measure: milliliter (mL)
1578.48  (80.75) 1442.2  (63.54) 1485.28  (70.19)
4.Secondary Outcome
Title Percent Change From Baseline in Mean Combined Liver and Spleen Volume at Week 53
Hide Description Liver and Spleen volume was determined by Magnetic Resonance Imaging (MRI). Change was calculated at Week 53 from baseline.
Time Frame Baseline, Week 53
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, number of participants analyzed = participants who were evaluable for this measure.
Arm/Group Title Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo
Hide Arm/Group Description:
Idursulfase 0.5 mg/kg administered once-weekly by intravenous infusion for one year (52 infusions).
Idursulfase 0.5 mg/kg administered every other week by intravenous infusion for one year (26 infusions) along with placebo matching to idursulfase every other week (alternating with idursulfase) by intravenous infusion for one year (26 infusions).
Placebo matching to idursulfase administered once-weekly by intravenous infusion for one year (52 infusions).
Overall Number of Participants Analyzed 31 29 30
Mean (Standard Error)
Unit of Measure: percent change
-25.81  (1.44) -23.73  (1.49) 0.27  (1.66)
5.Secondary Outcome
Title Change From Baseline in Mean Normalized Urine Glycosaminoglycan (GAG) Levels at Week 53
Hide Description Mean normalized urine GAG was analyzed using urine testing. Change was calculated at Week 53 from baseline. The urine GAG levels were normalized to urine creatinine and were reported as microgram GAG per milligram creatinine (mcg GAG/mg creatinine).
Time Frame Baseline, Week 53
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo
Hide Arm/Group Description:
Idursulfase 0.5 mg/kg administered once-weekly by intravenous infusion for one year (52 infusions).
Idursulfase 0.5 mg/kg administered every other week by intravenous infusion for one year (26 infusions) along with placebo matching to idursulfase every other week (alternating with idursulfase) by intravenous infusion for one year (26 infusions).
Placebo matching to idursulfase administered once-weekly by intravenous infusion for one year (52 infusions).
Overall Number of Participants Analyzed 32 32 32
Mean (Standard Error)
Unit of Measure: mcg GAG/mg creatinine
Baseline 325.59  (25.79) 338.08  (21.03) 419.40  (34.37)
Change at Week 53 -189.23  (25.76) -154.98  (17.18) 18.16  (29.94)
6.Secondary Outcome
Title Mean Cardiac Left Ventricular Mass Index (LVMI) at Baseline
Hide Description Cardiac LVMI was determined by echocardiography. LVMI is the left ventricular mass (LVM, in grams [g]) indexed to body surface area (BSA), in square meter [m^2]. LVMI (in gram per square meter [g/m^2]) = LVM divided by BSA.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, number of participants analyzed = participants who were evaluable for this measure.
Arm/Group Title Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo
Hide Arm/Group Description:
Idursulfase 0.5 mg/kg administered once-weekly by intravenous infusion for one year (52 infusions).
Idursulfase 0.5 mg/kg administered every other week by intravenous infusion for one year (26 infusions) along with placebo matching to idursulfase every other week (alternating with idursulfase) by intravenous infusion for one year (26 infusions).
Placebo matching to idursulfase administered once-weekly by intravenous infusion for one year (52 infusions).
Overall Number of Participants Analyzed 31 31 31
Mean (Standard Error)
Unit of Measure: gram per square meter (g/m^2)
105.18  (6.86) 89.42  (4.38) 95.55  (5.96)
7.Secondary Outcome
Title Percent Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 53
Hide Description Cardiac LVMI was determined by echocardiography. Change was calculated at Week 53 from baseline. LVMI is the LVM, in grams indexed to BSA, in square meter [m^2]. LVMI in g/m^2 = LVM divided by BSA.
Time Frame Baseline, Week 53
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population. Here, number of participants analyzed = participants who were evaluable for this measure.
Arm/Group Title Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo
Hide Arm/Group Description:
Idursulfase 0.5 mg/kg administered once-weekly by intravenous infusion for one year (52 infusions).
Idursulfase 0.5 mg/kg administered every other week by intravenous infusion for one year (26 infusions) along with placebo matching to idursulfase every other week (alternating with idursulfase) by intravenous infusion for one year (26 infusions).
Placebo matching to idursulfase administered once-weekly by intravenous infusion for one year (52 infusions).
Overall Number of Participants Analyzed 31 31 31
Mean (Standard Error)
Unit of Measure: percent change
-1.34  (5.05) 6.71  (4.03) 3.56  (4.12)
Time Frame 52 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo
Hide Arm/Group Description Idursulfase 0.5 mg/kg administered once-weekly by intravenous infusion for one year (52 infusions). Idursulfase 0.5 mg/kg administered every other week by intravenous infusion for one year (26 infusions) along with placebo matching to idursulfase every other week (alternating with idursulfase) by intravenous infusion for one year (26 infusions). Placebo matching to idursulfase administered once-weekly by intravenous infusion for one year (52 infusions).
All-Cause Mortality
Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/32 (28.13%)      8/32 (25.00%)      9/32 (28.13%)    
Cardiac disorders       
Aortic valve incompetence  1  1/32 (3.13%)  1 0/32 (0.00%)  0 1/32 (3.13%)  1
Arrhythmia not otherwise specified (nos)  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Atrial tachycardia  1  1/32 (3.13%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0
Cyanosis nos  1  1/32 (3.13%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0
Heart valve insufficiency  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Ear and labyrinth disorders       
Ear disorder nos  1  1/32 (3.13%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0
Hearing impaired  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Otorrhoea  1  1/32 (3.13%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0
Gastrointestinal disorders       
Appendicitis  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Nausea  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Pancreatitis acute  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Umbilical hernia nos  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
General disorders       
Hernia nos  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Pyrexia  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Infections and infestations       
Bronchopneumonia nos  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Localised infection  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Otitis media chronic nos  1  0/32 (0.00%)  0 0/32 (0.00%)  0 2/32 (6.25%)  2
Otitis media serous nos  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Pilonidal sinus infected  1  1/32 (3.13%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0
Pneumonia streptococcal  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Tooth caries nos  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Wound infection due to staphylococcus aureus  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Injury, poisoning and procedural complications       
Anaesthesia intubation complication  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Medical device complication  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Investigations       
Blood carbon dioxide increased  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/32 (3.13%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0
Nervous system disorders       
Carpal tunnel syndrome  1  1/32 (3.13%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0
Headache  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Psychiatric disorders       
Adjustment disorder with depressed mood  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Phobia  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Adenoidal hypertrophy  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Bronchospasm nos  1  1/32 (3.13%)  1 0/32 (0.00%)  0 1/32 (3.13%)  1
Epistaxis  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Pulmonary embolism  1  1/32 (3.13%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0
Respiratory failure  1  1/32 (3.13%)  1 0/32 (0.00%)  0 0/32 (0.00%)  0
Tonsillar hypertrophy  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Skin and subcutaneous tissue disorders       
Rash nos  1  0/32 (0.00%)  0 0/32 (0.00%)  0 1/32 (3.13%)  1
Vascular disorders       
Orthostatic hypotension  1  0/32 (0.00%)  0 1/32 (3.13%)  1 0/32 (0.00%)  0
Poor venous access  1  2/32 (6.25%)  2 3/32 (9.38%)  4 2/32 (6.25%)  2
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (5.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Idursulfase Weekly (0.5 mg/kg) Idursulfase EOW (0.5 mg/kg) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   32/32 (100.00%)      32/32 (100.00%)      32/32 (100.00%)    
Blood and lymphatic system disorders       
Lymphadenopathy  1  0/32 (0.00%)  0 2/32 (6.25%)  2 0/32 (0.00%)  0
Cardiac disorders       
Atrial hypertrophy  1  2/32 (6.25%)  2 0/32 (0.00%)  0 3/32 (9.38%)  3
Tachycardia nos  1  1/32 (3.13%)  1 3/32 (9.38%)  5 2/32 (6.25%)  10
Ventricular hypertrophy  1  2/32 (6.25%)  2 2/32 (6.25%)  2 1/32 (3.13%)  1
Ear and labyrinth disorders       
Cerumen impaction  1  0/32 (0.00%)  0 2/32 (6.25%)  2 2/32 (6.25%)  2
Deafness nos  1  1/32 (3.13%)  1 0/32 (0.00%)  0 2/32 (6.25%)  2
Deafness unilateral  1  0/32 (0.00%)  0 2/32 (6.25%)  2 0/32 (0.00%)  0
Ear disorder nos  1  2/32 (6.25%)  3 1/32 (3.13%)  1 0/32 (0.00%)  0
Ear haemorrhage  1  0/32 (0.00%)  0 0/32 (0.00%)  0 2/32 (6.25%)  3
Ear pain  1  7/32 (21.88%)  7 5/32 (15.63%)  9 6/32 (18.75%)  13
Eustachian tube dysfunction  1  1/32 (3.13%)  1 2/32 (6.25%)  5 0/32 (0.00%)  0
Hypoacusis  1  1/32 (3.13%)  1 5/32 (15.63%)  5 4/32 (12.50%)  5
Otorrhoea  1  7/32 (21.88%)  20 7/32 (21.88%)  17 9/32 (28.13%)  21
Sensation of block in ear  1  0/32 (0.00%)  0 3/32 (9.38%)  3 1/32 (3.13%)  1
Tympanic membrane perforation  1  0/32 (0.00%)  0 0/32 (0.00%)  0 2/32 (6.25%)  2
Eye disorders       
Conjunctivitis  1  1/32 (3.13%)  1 0/32 (0.00%)  0 3/32 (9.38%)  3
Conjunctivitis allergic  1  2/32 (6.25%)  2 1/32 (3.13%)  1 0/32 (0.00%)  0
Eye pain  1  3/32 (9.38%)  3 1/32 (3.13%)  1 1/32 (3.13%)  1
Hypermetropia  1  2/32 (6.25%)  2 0/32 (0.00%)  0 0/32 (0.00%)  0
Lacrimation increased  1  3/32 (9.38%)  6 0/32 (0.00%)  0 1/32 (3.13%)  2
Myopia  1  0/32 (0.00%)  0 2/32 (6.25%)  2 0/32 (0.00%)  0
Vision blurred  1  3/32 (9.38%)  5 0/32 (0.00%)  0 2/32 (6.25%)  2
Gastrointestinal disorders       
Abdominal discomfort  1  0/32 (0.00%)  0 2/32 (6.25%)  2 1/32 (3.13%)  1
Abdominal pain nos  1  11/32 (34.38%)  24 17/32 (53.13%)  36 11/32 (34.38%)  20
Abdominal pain upper  1  5/32 (15.63%)  14 2/32 (6.25%)  2 2/32 (6.25%)  3
Constipation  1  2/32 (6.25%)  4 1/32 (3.13%)  1 1/32 (3.13%)  2
Diarrhoea nos  1  11/32 (34.38%)  22 12/32 (37.50%)  24 15/32 (46.88%)  29
Dyspepsia  1  4/32 (12.50%)  5 4/32 (12.50%)  18 0/32 (0.00%)  0
Flatulence  1  0/32 (0.00%)  0 2/32 (6.25%)  13 1/32 (3.13%)  1
Gastroenteritis nos  1  1/32 (3.13%)  1 3/32 (9.38%)  4 3/32 (9.38%)  3
Gastrooesophageal reflux disease  1  1/32 (3.13%)  1 2/32 (6.25%)  2 0/32 (0.00%)  0
Inguinal hernia nos  1  0/32 (0.00%)  0 0/32 (0.00%)  0 2/32 (6.25%)  2
Loose stools  1  1/32 (3.13%)  1 0/32 (0.00%)  0 2/32 (6.25%)  4
Nausea  1  7/32 (21.88%)  18 9/32 (28.13%)  16 9/32 (28.13%)  17
Swollen tongue  1  2/32 (6.25%)  2 0/32 (0.00%)  0 0/32 (0.00%)  0
Toothache  1  2/32 (6.25%)  2 0/32 (0.00%)  0 2/32 (6.25%)  2
Umbilical hernia nos  1  0/32 (0.00%)  0 2/32 (6.25%)  2 1/32 (3.13%)  1
Vomiting nos  1  8/32 (25.00%)  22 18/32 (56.25%)  37 16/32 (50.00%)  43
General disorders       
Asthenia  1  3/32 (9.38%)  3 1/32 (3.13%)  1 0/32 (0.00%)  0
Catheter site pain  1  0/32 (0.00%)  0 2/32 (6.25%)  3 3/32 (9.38%)  3
Chest pain  1  3/32 (9.38%)  7 2/32 (6.25%)  2 0/32 (0.00%)  0
Fall  1  0/32 (0.00%)  0 4/32 (12.50%)  7 4/32 (12.50%)  10
Fatigue  1  2/32 (6.25%)  2 4/32 (12.50%)  10 3/32 (9.38%)  5
Gait abnormal  1  0/32 (0.00%)  0 1/32 (3.13%)  1 2/32 (6.25%)  2
Hernia pain  1  1/32 (3.13%)  1 2/32 (6.25%)  3 1/32 (3.13%)  2
Inflammation localised  1  2/32 (6.25%)  3 0/32 (0.00%)  0 1/32 (3.13%)  1
Influenza like illness  1  3/32 (9.38%)  7 8/32 (25.00%)  12 4/32 (12.50%)  6
Infusion site pain  1  3/32 (9.38%)  5 3/32 (9.38%)  3 2/32 (6.25%)  2
Infusion site swelling  1  4/32 (12.50%)  6 4/32 (12.50%)  4 1/32 (3.13%)  1
Injection site bruising  1  0/32 (0.00%)  0 2/32 (6.25%)  3 0/32 (0.00%)  0
Injection site extravasation  1  2/32 (6.25%)  2 2/32 (6.25%)  3 2/32 (6.25%)  3
Injection site haemorrhage  1  1/32 (3.13%)  1 0/32 (0.00%)  0 2/32 (6.25%)  2
Lethargy  1  2/32 (6.25%)  4 0/32 (0.00%)  0 0/32 (0.00%)  0
Malaise  1  5/32 (15.63%)  7 1/32 (3.13%)  1 3/32 (9.38%)  3
Oedema peripheral  1  2/32 (6.25%)  11 0/32 (0.00%)  0 1/32 (3.13%)  1
Pain nos  1  1/32 (3.13%)  1 1/32 (3.13%)  1 2/32 (6.25%)  2
Pyrexia  1  20/32 (62.50%)  83 18/32 (56.25%)  68 19/32 (59.38%)  63
Rigors  1  1/32 (3.13%)  1 3/32 (9.38%)  8 1/32 (3.13%)  1
Sensation of foreign body nos  1  2/32 (6.25%)  2 0/32 (0.00%)  0 0/32 (0.00%)  0
Infections and infestations       
Ear infection nos  1  8/32 (25.00%)  15 9/32 (28.13%)  17 9/32 (28.13%)  19
Furuncle  1  1/32 (3.13%)  1 2/32 (6.25%)  3 1/32 (3.13%)  1
Herpes simplex  1  2/32 (6.25%)  2 1/32 (3.13%)  4 0/32 (0.00%)  0
Hordeolum  1  0/32 (0.00%)  0 2/32 (6.25%)  2 3/32 (9.38%)  3
Influenza  1  2/32 (6.25%)  2 1/32 (3.13%)  1 1/32 (3.13%)  2
Lice infestation  1  2/32 (6.25%)  2 0/32 (0.00%)  0 2/32 (6.25%)  2
Localised infection  1  0/32 (0.00%)  0 3/32 (9.38%)  3 0/32 (0.00%)  0
Lower respiratory tract infection nos  1  0/32 (0.00%)  0 2/32 (6.25%)  2 1/32 (3.13%)  1
Otitis media nos  1  6/32 (18.75%)  8 7/32 (21.88%)  11 7/32 (21.88%)  9
Otitis media serous nos  1  4/32 (12.50%)  8 2/32 (6.25%)  7 4/32 (12.50%)  6
Respiratory tract infection nos  1  1/32 (3.13%)  1 2/32 (6.25%)  2 1/32 (3.13%)  1
Sinusitis nos  1  5/32 (15.63%)  5 2/32 (6.25%)  5 3/32 (9.38%)  4
Tonsillitis  1  2/32 (6.25%)  2 3/32 (9.38%)  3 1/32 (3.13%)  1
Tracheobronchitis  1  1/32 (3.13%)  1 1/32 (3.13%)  1 3/32 (9.38%)  4
Upper respiratory tract infection nos  1  12/32 (37.50%)  26 12/32 (37.50%)  34 10/32 (31.25%)  19
Urinary tract infection nos  1  2/32 (6.25%)  3 0/32 (0.00%)  0 0/32 (0.00%)  0
Varicella  1  2/32 (6.25%)  2 0/32 (0.00%)  0 0/32 (0.00%)  0
Viral infection nos  1  1/32 (3.13%)  1 1/32 (3.13%)  1 2/32 (6.25%)  2
Injury, poisoning and procedural complications       
Abrasion nos  1  0/32 (0.00%)  0 3/32 (9.38%)  6 3/32 (9.38%)  6
Arthropod bite  1  3/32 (9.38%)  5 1/32 (3.13%)  1 0/32 (0.00%)  0
Head injury  1  0/32 (0.00%)  0 4/32 (12.50%)  5 1/32 (3.13%)  1
Muscle strain  1  0/32 (0.00%)  0 2/32 (6.25%)  2 0/32 (0.00%)  0
Post procedural pain  1  2/32 (6.25%)  3 3/32 (9.38%)  5 3/32 (9.38%)  3
Skin laceration  1  2/32 (6.25%)  2 3/32 (9.38%)  3 1/32 (3.13%)  1
Investigations       
Alanine aminotransferase increased  1  0/32 (0.00%)  0 0/32 (0.00%)  0 4/32 (12.50%)  6
Aspartate aminotransferase increased  1  0/32 (0.00%)  0 0/32 (0.00%)  0 3/32 (9.38%)  3
Blood alkaline phosphatase nos increased  1  1/32 (3.13%)  1 2/32 (6.25%)  2 2/32 (6.25%)  2
Blood lactate dehydrogenase increased  1  1/32 (3.13%)  1 2/32 (6.25%)  3 0/32 (0.00%)  0
Blood triglycerides increased  1  0/32 (0.00%)  0 2/32 (6.25%)  2 0/32 (0.00%)  0
Electrocardiogram abnormal nos  1  1/32 (3.13%)  1 2/32 (6.25%)  2 0/32 (0.00%)  0
Gamma-Glutamyltransferase increased  1  0/32 (0.00%)  0 0/32 (0.00%)  0 2/32 (6.25%)  3
Haematocrit decreased  1  0/32 (0.00%)  0 0/32 (0.00%)  0 2/32 (6.25%)  2
Haemoglobin decreased  1  1/32 (3.13%)  1 0/32 (0.00%)  0 2/32 (6.25%)  2
Metabolism and nutrition disorders       
Appetite decreased nos  1  1/32 (3.13%)  1 2/32 (6.25%)  2 1/32 (3.13%)  3
Hypokalaemia  1  2/32 (6.25%)  2 0/32 (0.00%)  0 1/32 (3.13%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia  1  10/32 (31.25%)  26 14/32 (43.75%)  28 9/32 (28.13%)  15
Back pain  1  8/32 (25.00%)  10 11/32 (34.38%)  25 8/32 (25.00%)  11
Bone pain  1  2/32 (6.25%)  2 1/32 (3.13%)  1 0/32 (0.00%)  0
Chest wall pain  1  4/32 (12.50%)  4 0/32 (0.00%)  0 0/32 (0.00%)  0
Groin pain  1  1/32 (3.13%)  1 2/32 (6.25%)  4 0/32 (0.00%)  0
Muscle cramp  1  2/32 (6.25%)  3 3/32 (9.38%)  4 1/32 (3.13%)  1
Musculoskeletal chest pain  1  1/32 (3.13%)  1 3/32 (9.38%)  3 0/32 (0.00%)  0
Myalgia  1  3/32 (9.38%)  3 4/32 (12.50%)  8 3/32 (9.38%)  4
Neck pain  1  3/32 (9.38%)  4 4/32 (12.50%)  4 3/32 (9.38%)  7
Pain in foot  1  2/32 (6.25%)  2 1/32 (3.13%)  3 2/32 (6.25%)  2
Pain in limb  1  9/32 (28.13%)  20 9/32 (28.13%)  18 10/32 (31.25%)  14
Peripheral swelling  1  1/32 (3.13%)  1 4/32 (12.50%)  4 2/32 (6.25%)  3
Nervous system disorders       
Carpal tunnel syndrome  1  2/32 (6.25%)  2 0/32 (0.00%)  0 1/32 (3.13%)  1
Dizziness  1  4/32 (12.50%)  10 6/32 (18.75%)  9 8/32 (25.00%)  16
Headache  1  19/32 (59.38%)  132 21/32 (65.63%)  118 14/32 (43.75%)  80
Hyperreflexia  1  1/32 (3.13%)  1 2/32 (6.25%)  2 1/32 (3.13%)  1
Hypoaesthesia  1  0/32 (0.00%)  0 1/32 (3.13%)  1 2/32 (6.25%)  2
Insomnia  1  1/32 (3.13%)  1 3/32 (9.38%)  22 1/32 (3.13%)  3
Migraine nos  1  2/32 (6.25%)  2 0/32 (0.00%)  0 1/32 (3.13%)  3
Paraesthesia  1  2/32 (6.25%)  6 2/32 (6.25%)  2 1/32 (3.13%)  3
Post-Traumatic headache  1  0/32 (0.00%)  0 2/32 (6.25%)  3 0/32 (0.00%)  0
Somnolence  1  0/32 (0.00%)  0 3/32 (9.38%)  3 1/32 (3.13%)  1
Tremor  1  2/32 (6.25%)  4 1/32 (3.13%)  1 1/32 (3.13%)  1
Psychiatric disorders       
Abnormal behaviour nos  1  2/32 (6.25%)  2 0/32 (0.00%)  0 3/32 (9.38%)  3
Anxiety  1  2/32 (6.25%)  4 4/32 (12.50%)  5 0/32 (0.00%)  0
Depression  1  3/32 (9.38%)  3 2/32 (6.25%)  2 0/32 (0.00%)  0
Renal and urinary disorders       
Haematuria  1  2/32 (6.25%)  2 0/32 (0.00%)  0 0/32 (0.00%)  0
Reproductive system and breast disorders       
Testicular pain  1  0/32 (0.00%)  0 2/32 (6.25%)  2 0/32 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Asthma nos  1  3/32 (9.38%)  4 1/32 (3.13%)  3 2/32 (6.25%)  4
Bronchitis nos  1  1/32 (3.13%)  1 1/32 (3.13%)  1 2/32 (6.25%)  2
Bronchospasm nos  1  3/32 (9.38%)  5 2/32 (6.25%)  5 4/32 (12.50%)  11
Cough  1  16/32 (50.00%)  30 16/32 (50.00%)  38 19/32 (59.38%)  42
Dyspnoea nos  1  4/32 (12.50%)  10 3/32 (9.38%)  3 9/32 (28.13%)  11
Epistaxis  1  2/32 (6.25%)  2 1/32 (3.13%)  5 4/32 (12.50%)  5
Hypoxia  1  1/32 (3.13%)  2 3/32 (9.38%)  4 1/32 (3.13%)  1
Nasal congestion  1  12/32 (37.50%)  18 16/32 (50.00%)  39 12/32 (37.50%)  23
Nasal passage irritation  1  2/32 (6.25%)  2 0/32 (0.00%)  0 0/32 (0.00%)  0
Nasopharyngitis  1  4/32 (12.50%)  5 8/32 (25.00%)  16 5/32 (15.63%)  15
Obstructive airways disorder nos  1  2/32 (6.25%)  2 0/32 (0.00%)  0 0/32 (0.00%)  0
Pharyngitis  1  13/32 (40.63%)  19 11/32 (34.38%)  23 10/32 (31.25%)  18
Respiratory tract congestion  1  1/32 (3.13%)  1 2/32 (6.25%)  2 2/32 (6.25%)  3
Rhinitis allergic nos  1  3/32 (9.38%)  7 3/32 (9.38%)  3 3/32 (9.38%)  6
Rhinitis nos  1  4/32 (12.50%)  5 0/32 (0.00%)  0 4/32 (12.50%)  4
Rhinorrhoea  1  9/32 (28.13%)  14 10/32 (31.25%)  19 9/32 (28.13%)  20
Rhonchi  1  3/32 (9.38%)  3 4/32 (12.50%)  4 5/32 (15.63%)  9
Sleep apnoea syndrome  1  2/32 (6.25%)  2 1/32 (3.13%)  1 1/32 (3.13%)  1
Sneezing  1  3/32 (9.38%)  3 2/32 (6.25%)  2 3/32 (9.38%)  4
Tachypnoea  1  2/32 (6.25%)  3 0/32 (0.00%)  0 2/32 (6.25%)  3
Upper respiratory tract congestion  1  1/32 (3.13%)  1 1/32 (3.13%)  1 2/32 (6.25%)  4
Wheezing  1  5/32 (15.63%)  6 5/32 (15.63%)  7 5/32 (15.63%)  8
Skin and subcutaneous tissue disorders       
Acne nos  1  3/32 (9.38%)  3 2/32 (6.25%)  2 0/32 (0.00%)  0
Contusion  1  2/32 (6.25%)  2 5/32 (15.63%)  6 2/32 (6.25%)  2
Dyshidrosis  1  0/32 (0.00%)  0 2/32 (6.25%)  2 0/32 (0.00%)  0
Eczema  1  2/32 (6.25%)  3 0/32 (0.00%)  0 1/32 (3.13%)  2
Erythema  1  2/32 (6.25%)  12 1/32 (3.13%)  3 1/32 (3.13%)  1
Pruritus  1  10/32 (31.25%)  19 6/32 (18.75%)  14 5/32 (15.63%)  10
Rash macular  1  2/32 (6.25%)  2 0/32 (0.00%)  0 1/32 (3.13%)  1
Rash nos  1  8/32 (25.00%)  14 11/32 (34.38%)  39 10/32 (31.25%)  29
Rash pruritic  1  5/32 (15.63%)  9 5/32 (15.63%)  6 0/32 (0.00%)  0
Sweating increased  1  2/32 (6.25%)  3 2/32 (6.25%)  2 3/32 (9.38%)  3
Urticaria nos  1  5/32 (15.63%)  10 4/32 (12.50%)  9 0/32 (0.00%)  0
Vascular disorders       
Flushing  1  5/32 (15.63%)  9 5/32 (15.63%)  9 6/32 (18.75%)  7
Hypertension nos  1  8/32 (25.00%)  23 5/32 (15.63%)  7 7/32 (21.88%)  10
Hypotension nos  1  3/32 (9.38%)  5 2/32 (6.25%)  4 4/32 (12.50%)  9
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (5.1)
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.
Results Point of Contact
Name/Title: Study Physician
Organization: Shire
Phone: 1 866-842-5335
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT00069641     History of Changes
Other Study ID Numbers: TKT024
First Submitted: September 29, 2003
First Posted: October 1, 2003
Results First Submitted: January 16, 2014
Results First Posted: May 13, 2015
Last Update Posted: May 13, 2015