ClinicalTrials.gov
ClinicalTrials.gov Menu

Randomized, Controlled, Open-label, Multicenter, Safety and Efficacy Study of rhHNS Administration Via an IDDD in Pediatric Patients With Early Stage MPS IIIA 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: NCT02060526
Recruitment Status : Completed
First Posted : February 12, 2014
Results First Posted : March 3, 2017
Last Update Posted : May 15, 2017
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Sanfilippo Syndrome
Intervention Drug: Recombinant human heparan N-sulfatase [rhHNS]
Enrollment 21
Recruitment Details  
Pre-assignment Details A total of 24 participants were screened, of them 21 participants were enrolled in the study.
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description Participants received no treatment (HGT-1410). Participants received HGT-1410 45 milligram (mg) intrathecally once every two weeks (Q2W) using surgically implanted intrathecal drug delivery device (IDDD) or lumbar puncture (LP) for 48 weeks. Participants received HGT-1410 45 mg intrathecally once every four weeks (Q4W) using surgically implanted IDDD or LP for 48 weeks.
Period Title: Overall Study
Started 7 7 7
Completed 7 7 7
Not Completed 0 0 0
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W Total
Hide Arm/Group Description Participants received no treatment (HGT-1410). Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks. Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks. Total of all reporting groups
Overall Number of Baseline Participants 7 7 7 21
Hide Baseline Analysis Population Description
Intent-to-treat (ITT) population included all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 7 participants 7 participants 7 participants 21 participants
32.42  (9.548) 29.64  (9.989) 33.53  (9.336) 31.87  (9.287)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 7 participants 7 participants 21 participants
Female
3
  42.9%
5
  71.4%
4
  57.1%
12
  57.1%
Male
4
  57.1%
2
  28.6%
3
  42.9%
9
  42.9%
1.Primary Outcome
Title Number of Participants With Overall Response Using Bayley Scales of Infant Development Assessment Third Edition (BSID-III)
Hide Description The BSID-­III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. The development quotient (DQ) is a means to express a neurodevelopmental/cognitive delay which was computed as a ratio and expressed as a percentage using the age equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range: 0, 100). The BSID-­III DQ score is based on the cognitive domain. A positive value indicates improvement in health and cognition. Overall response was the maximum decline in the DQ of 10 points or less over 48 weeks. Number of participants with the overall response were reported here.
Time Frame Baseline (Week 0) up to Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received no treatment (HGT-1410).
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7 7
Measure Type: Number
Unit of Measure: participants
0 2 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection No HGT-1410, HGT-1410 45 mg Q2W
Comments 95% exact unconditional confidence interval of the difference in proportion between each of the treatment groups and the untreated control group was considered for the parameter estimation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4615
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between proportions
Estimated Value 0.286
Confidence Interval (2-Sided) 95%
-0.297 to 0.745
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection No HGT-1410, HGT-1410 45 mg Q4W
Comments 95% exact unconditional confidence interval of the difference in proportion between each of the treatment groups and the untreated control group was considered for the parameter estimation.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference between proportions
Estimated Value 0.143
Confidence Interval (2-Sided) 95%
-0.423 to 0.647
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAE)
Hide Description An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product related. This included an exacerbation of a pre-existing condition. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Time Frame Baseline (Week 0) up to Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received a dose of HGT-1410 either using IDDD implantation or LP; underwent the IDDD surgical implant procedure without receiving a dose of HGT-1410; were randomly assigned to the untreated group and had any safety follow-up data.
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received no treatment (HGT-1410).
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7 7
Measure Type: Number
Unit of Measure: participants
3 5 6
3.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Hide Description An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product related. This included an exacerbation of a pre-existing condition. TEAEs were defined as AE occurring on or after the time of first IDDD implantation or LP procedure to the end of study (EOS) visit (+30 days).
Time Frame Baseline (Week 0) up to Week 52
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received a dose of HGT-1410 using the IDDD implantation or LP; underwent the IDDD surgical implant procedure without receiving a dose of HGT-1410; were randomly assigned to the untreated group and had any safety follow-up data.
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received no treatment (HGT-1410).
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7 7
Measure Type: Number
Unit of Measure: participants
6 7 7
4.Secondary Outcome
Title Number of Participants With Positive Anti-recombinant Human Heparan-N-Sulfatase (rhHNS) Antibody in Serum at Week 48
Hide Description A participant was considered positive if they had at least 1 positive result during the study. Once a participant reported antibody positive, they were considered positive for the remainder of the study.
Time Frame Baseline (Week 0) up to Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population included all participants who received a dose of HGT-1410 using either the IDDD implantation or LP; underwent the IDDD surgical implant procedure without receiving a dose of HGT-1410; were randomly assigned to the untreated group and had any safety followup data.
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received no treatment (HGT-1410).
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7 7
Measure Type: Number
Unit of Measure: participants
1 7 6
5.Secondary Outcome
Title Change From Baseline in Vineland Adaptive Behavior Scales Second Edition (VABS-II) Development Quotient (DQ) Score at Week 48
Hide Description The VABS-II test measures adaptive behaviors, including the ability to cope with environmental changes, to learn new everyday skills, and to demonstrate independence. The DQ is a means to express a neurodevelopmental/cognitive delay. The DQ was computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range, 0, 100). The overall DQ score is calculated from the mean age-equivalent score obtained by averaging out the age-equivalent scores for the all the sub-domains except for Gross and Fine motor skills. This test measures the following 5 key domains: communication, daily living skills, socialization, motor skills, and the adaptive behavior composite (a composite of the other 4 domains). A positive value indicates improvement in health and cognition.
Time Frame Baseline (Week 0), Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received no treatment (HGT-1410).
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7 7
Mean (Standard Deviation)
Unit of Measure: percentage of chronological age
Communication Domain Number Analyzed 7 participants 6 participants 7 participants
-5.12  (10.981) -20.83  (23.475) -4.97  (17.253)
Daily Living Skills Domain Number Analyzed 6 participants 6 participants 6 participants
-4.20  (29.005) -27.09  (21.444) -11.74  (26.713)
Socialization Domain Number Analyzed 6 participants 6 participants 6 participants
-16.12  (23.320) -24.24  (40.617) -29.34  (29.425)
Motor Skills Domain Number Analyzed 6 participants 6 participants 6 participants
-5.37  (24.741) -27.01  (20.820) -17.88  (12.007)
6.Secondary Outcome
Title Change From Baseline in Development Quotient (DQ) Using Bayley Scales of Infant Development Assessment Third Edition (BSID-III) at Week 48
Hide Description The BSID-­III is a series of measurements to assess the motor (fine and gross), language (receptive and expressive), and cognitive development of infants and toddlers and consists of a series of developmental play tasks. The DQ is a means to express a neurodevelopmental/cognitive delay which was computed as a ratio and expressed as a percentage using the age-equivalent score divided by the age at testing ([age-equivalent score/chronological age] × 100; range: 0, 100). The BSID-­III DQ score is based on the cognitive domain. A positive value indicates improvement in health and cognition.
Time Frame Baseline (Week 0), Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received no treatment (HGT-1410).
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7 7
Mean (Standard Deviation)
Unit of Measure: percentage of chronological age
Cognitive -19.81  (3.974) -23.82  (14.684) -19.87  (12.724)
Receptive Communication -13.15  (13.318) -16.33  (25.373) -12.41  (14.981)
Expressive Communication -14.77  (10.055) -19.71  (22.878) -10.01  (15.573)
Fine Motor -23.72  (14.752) -18.59  (18.879) -18.86  (16.308)
Gross Motor -11.60  (13.668) -12.52  (21.203) -2.77  (18.947)
7.Secondary Outcome
Title Change From Baseline in Total Cortical Grey Matter Volume at Week 48
Hide Description The change from baseline in grey matter volume at Week 48 was assessed by magnetic resonance imaging (MRI).
Time Frame Baseline (Week 0), Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received no treatment (HGT-1410).
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7 7
Mean (Standard Deviation)
Unit of Measure: cubic centimeter (cc)
-45.1  (23.35) -102.0  (68.12) -58.8  (66.24)
8.Secondary Outcome
Title Change From Baseline in Concentration of Glycosaminoglycan (GAG) in Cerebrospinal Fluid (CSF) at Week 48
Hide Description Change from baseline in concentration of GAG in CSF at Week 48 was reported.
Time Frame Baseline (Week 0), Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received no treatment (HGT-1410).
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7 7
Mean (Standard Deviation)
Unit of Measure: micromolar
-0.193  (1.318) -6.888  (5.388) -5.924  (2.470)
9.Secondary Outcome
Title Change From Baseline in Concentration of GAG in Urine at Week 48
Hide Description The concentration of GAG in urine was normalized to the urine creatinine value and reported as milligram (mg) GAG per millimole (mmol) creatinine.
Time Frame Baseline (Week 0), Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population included all randomized participants.
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received no treatment (HGT-1410).
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7 7
Mean (Standard Deviation)
Unit of Measure: mg GAG/mmol creatinine
-7.18  (39.175) -31.81  (22.887) -42.46  (29.861)
10.Secondary Outcome
Title Concentration of Recombinant Human Heparan-N-Sulfatase (rhHNS) in Cerebrospinal Fluid (CSF)
Hide Description Concentration of rhHNS in CSF was assessed using validated enzyme-linked immunosorbent assay (ELISA) method.
Time Frame Pre-dose, 4, 48 hours on Week 0 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population included all participants who received HGT-1410, participated in the scheduled PK studies, and had sufficient samples available for analysis.
Arm/Group Title HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/ml)
Week 0: Predose Number Analyzed 7 participants 7 participants
0  (0) 0  (0)
Week 0: 4h Number Analyzed 5 participants 5 participants
313392.49  (142748.885) 266021.60  (113340.887)
Week 0: 48h Number Analyzed 6 participants 6 participants
366.05  (571.528) 2119.59  (2068.093)
Week 48: Predose Number Analyzed 6 participants 7 participants
869.67  (1863.989) 365.04  (965.797)
Week 48: 4h Number Analyzed 5 participants 5 participants
374544.38  (135047.700) 335203.84  (82918.537)
Week 48: 48h Number Analyzed 4 participants 5 participants
104.49  (65.881) 8892.93  (19519.717)
11.Secondary Outcome
Title Maximum Observed Drug Concentration (Cmax) of Recombinant Human Heparan-N-Sulfatase (rhHNS) in Serum
Hide Description Cmax of rhHNS in serum was evaluated using enzyme-linked immunosorbent assay (ELISA) method and liquid chromatography tandem mass spectrometry (LC-MS) method.
Time Frame Predose, 0.5 h, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h, and 48 h post-dose on Week 0 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) population included all participants who received HGT-1410, participated in the scheduled PK studies, and had sufficient samples available for analysis.
Arm/Group Title HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description:
Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks.
Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
Overall Number of Participants Analyzed 7 7
Mean (Standard Deviation)
Unit of Measure: ng/ml
ELISA Method: Week 0 Number Analyzed 7 participants 7 participants
120.9  (84.77) 237.0  (159.68)
ELISA Method: Week 48 Number Analyzed 7 participants 4 participants
63.5  (149.76) 118.8  (161.98)
LC-MS Method: Week 0 Number Analyzed 7 participants 7 participants
102.4  (63.00) 191.0  (125.84)
LC-MS Method: Week 48 Number Analyzed 7 participants 5 participants
188.1  (127.40) 119.7  (133.18)
Time Frame From start of study drug administration up to Week 52
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Hide Arm/Group Description Participants received no treatment (HGT-1410). Participants received HGT-1410 45 mg intrathecally Q2W using surgically implanted IDDD or LP for 48 weeks. Participants received HGT-1410 45 mg intrathecally Q4W using surgically implanted IDDD or LP for 48 weeks.
All-Cause Mortality
No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/7 (42.86%)      5/7 (71.43%)      6/7 (85.71%)    
Gastrointestinal disorders       
Haematemesis * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Vomiting * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
General disorders       
Adverse drug reaction * 1  0/7 (0.00%)  0 1/7 (14.29%)  8 0/7 (0.00%)  0
Asthenia * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Device breakage * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Device failure * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 1/7 (14.29%)  1
Implant site extravasation * 1  0/7 (0.00%)  0 2/7 (28.57%)  3 0/7 (0.00%)  0
Implant site pain * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Infections and infestations       
Central nervous system infection * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Gastroenteritis viral * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Gastrointestinal infection * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Implant site infection * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Influenza * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Pneumonia * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Postoperative wound infection * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Skin infection * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Urinary tract infection * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Viral upper respiratory tract infection * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Wound infection * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Injury, poisoning and procedural complications       
Incision site swelling * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Tooth injury * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Nervous system disorders       
Cerebrospinal fluid leakage * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 2/7 (28.57%)  2
Somnolence * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Psychiatric disorders       
Irritability * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Respiratory, thoracic and mediastinal disorders       
Sleep apnoea syndrome * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
No HGT-1410 HGT-1410 45 mg Q2W HGT-1410 45 mg Q4W
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/7 (85.71%)      7/7 (100.00%)      7/7 (100.00%)    
Blood and lymphatic system disorders       
Leukopenia * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Cardiac disorders       
Bradycardia * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Left ventricular hypertrophy * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Sinus tachycardia * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Ear and labyrinth disorders       
Motion sickness * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Otorrhoea * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Gastrointestinal disorders       
Abdominal pain * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Constipation * 1  0/7 (0.00%)  0 1/7 (14.29%)  2 0/7 (0.00%)  0
Diarrhoea * 1  1/7 (14.29%)  1 1/7 (14.29%)  1 2/7 (28.57%)  2
Dysphagia * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Enteritis * 1  1/7 (14.29%)  1 2/7 (28.57%)  4 0/7 (0.00%)  0
Gastrointestinal disorder * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Nausea * 1  0/7 (0.00%)  0 1/7 (14.29%)  2 0/7 (0.00%)  0
Salivary gland enlargement * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Salivary hypersecretion * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Vomiting * 1  1/7 (14.29%)  2 5/7 (71.43%)  12 3/7 (42.86%)  4
General disorders       
Adverse drug reaction * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Catheter site haemorrhage * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Developmental delay * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Impaired healing * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Implant site erythema * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Implant site extravasation * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 2/7 (28.57%)  4
Implant site swelling * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Local swelling * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Pyrexia * 1  4/7 (57.14%)  10 4/7 (57.14%)  22 4/7 (57.14%)  5
Hepatobiliary disorders       
Liver disorder * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Immune system disorders       
Drug hypersensitivity * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Seasonal allergy * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Infections and infestations       
Acute tonsillitis * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Bronchitis * 1  1/7 (14.29%)  4 0/7 (0.00%)  0 0/7 (0.00%)  0
Conjunctivitis * 1  1/7 (14.29%)  1 1/7 (14.29%)  1 1/7 (14.29%)  1
Ear infection * 1  2/7 (28.57%)  3 0/7 (0.00%)  0 4/7 (57.14%)  6
Gastroenteritis * 1  1/7 (14.29%)  1 1/7 (14.29%)  3 1/7 (14.29%)  2
Gastroenteritis viral * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Gastrointestinal infection * 1  1/7 (14.29%)  1 2/7 (28.57%)  2 0/7 (0.00%)  0
Hand-Foot-And-Mouth disease * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Implant site infection * 1  0/7 (0.00%)  0 1/7 (14.29%)  2 1/7 (14.29%)  1
Influenza * 1  1/7 (14.29%)  1 1/7 (14.29%)  1 0/7 (0.00%)  0
Meningitis aseptic * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Nasopharyngitis * 1  3/7 (42.86%)  6 0/7 (0.00%)  0 2/7 (28.57%)  4
Oral candidiasis * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Otitis media * 1  0/7 (0.00%)  0 3/7 (42.86%)  3 1/7 (14.29%)  1
Otitis media acute * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Pharyngitis * 1  2/7 (28.57%)  4 1/7 (14.29%)  3 1/7 (14.29%)  1
Respiratory syncytial virus infection * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Rhinitis * 1  2/7 (28.57%)  3 3/7 (42.86%)  4 1/7 (14.29%)  2
Scarlet fever * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Sinusitis * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 2/7 (28.57%)  2
Stitch abscess * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Tinea pedis * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Tonsillitis bacterial * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Tonsillitis streptococcal * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Tooth abscess * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Upper respiratory tract infection * 1  2/7 (28.57%)  6 5/7 (71.43%)  18 1/7 (14.29%)  2
Viral infection * 1  0/7 (0.00%)  0 1/7 (14.29%)  2 0/7 (0.00%)  0
Viral upper respiratory tract infection * 1  1/7 (14.29%)  1 1/7 (14.29%)  2 1/7 (14.29%)  1
Injury, poisoning and procedural complications       
Airway complication of anaesthesia * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Arthropod bite * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 1/7 (14.29%)  1
Contusion * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Craniocerebral injury * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 2/7 (28.57%)  2
Fall * 1  1/7 (14.29%)  1 3/7 (42.86%)  3 1/7 (14.29%)  1
Head injury * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Incision site complication * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Limb injury * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Postoperative fever * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Procedural dizziness * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Procedural headache * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Procedural hypotension * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Procedural pain * 1  1/7 (14.29%)  1 3/7 (42.86%)  4 0/7 (0.00%)  0
Stab wound * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Subdural haematoma * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 1/7 (14.29%)  1
Tooth fracture * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Tooth injury * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Wound complication * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Investigations       
Blood alkaline phosphatase increased * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Blood creatine phosphokinase increased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  2
Blood pressure decreased * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Blood pressure diastolic decreased * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 1/7 (14.29%)  5
Blood pressure diastolic increased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  3
Blood pressure increased * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Blood pressure systolic decreased * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 1/7 (14.29%)  10
Blood pressure systolic increased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  2
Body temperature decreased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  3
Crystal urine present * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Csf protein increased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Csf test abnormal * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Csf white blood cell count increased * 1  0/7 (0.00%)  0 1/7 (14.29%)  2 3/7 (42.86%)  3
Haematocrit decreased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Haemoglobin decreased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Heart rate decreased * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 1/7 (14.29%)  2
Heart rate increased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  8
Hepatic enzyme increased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Oxygen saturation decreased * 1  1/7 (14.29%)  1 1/7 (14.29%)  5 1/7 (14.29%)  2
Platelet count decreased * 1  0/7 (0.00%)  0 1/7 (14.29%)  2 0/7 (0.00%)  0
Protein total increased * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Red blood cell count decreased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Respiratory rate decreased * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  2
Urine uric acid * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Metabolism and nutrition disorders       
Hypokalaemia * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Iron deficiency * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Vitamin d deficiency * 1  0/7 (0.00%)  0 2/7 (28.57%)  2 0/7 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Back pain * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Rickets * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Nervous system disorders       
Aphasia * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Cerebral atrophy * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Cerebrospinal fluid leakage * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Cognitive disorder * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Demyelination * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Drooling * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Headache * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Motor dysfunction * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Psychomotor hyperactivity * 1  0/7 (0.00%)  0 2/7 (28.57%)  2 0/7 (0.00%)  0
Psychiatric disorders       
Agitation * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 0/7 (0.00%)  0
Attention deficit/hyperactivity disorder * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Insomnia * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 1/7 (14.29%)  1
Irritability * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Sleep disorder * 1  1/7 (14.29%)  1 1/7 (14.29%)  1 0/7 (0.00%)  0
Sleep terror * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Reproductive system and breast disorders       
Vulvovaginal erythema * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Bronchospasm * 1  1/7 (14.29%)  2 1/7 (14.29%)  2 0/7 (0.00%)  0
Cough * 1  1/7 (14.29%)  2 1/7 (14.29%)  1 0/7 (0.00%)  0
Nasal congestion * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Nasal obstruction * 1  1/7 (14.29%)  1 1/7 (14.29%)  1 0/7 (0.00%)  0
Rhinitis allergic * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Rhinorrhoea * 1  2/7 (28.57%)  2 1/7 (14.29%)  1 1/7 (14.29%)  1
Sinus disorder * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Skin and subcutaneous tissue disorders       
Dermatitis contact * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Dermatitis diaper * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Dry skin * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Ecchymosis * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Mucocutaneous rash * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  2
Pityriasis rosea * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Pruritus * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Rash * 1  0/7 (0.00%)  0 2/7 (28.57%)  2 0/7 (0.00%)  0
Rash macular * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Vascular disorders       
Diastolic hypertension * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  1
Diastolic hypotension * 1  1/7 (14.29%)  1 0/7 (0.00%)  0 1/7 (14.29%)  1
Haematoma * 1  0/7 (0.00%)  0 1/7 (14.29%)  1 0/7 (0.00%)  0
Systolic hypertension * 1  0/7 (0.00%)  0 0/7 (0.00%)  0 1/7 (14.29%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 17.1
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.
If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
Results Point of Contact
Name/Title: Study Physician
Organization: Shire
Phone: ClinicalTransparency@shire.com
Responsible Party: Shire
ClinicalTrials.gov Identifier: NCT02060526     History of Changes
Other Study ID Numbers: HGT-SAN-093
2013-003450-24 ( EudraCT Number )
First Submitted: February 10, 2014
First Posted: February 12, 2014
Results First Submitted: January 11, 2017
Results First Posted: March 3, 2017
Last Update Posted: May 15, 2017