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An Open-Label Extension Study of GA-GCB ERT in Patients With Type 1 Gaucher 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: NCT00635427
Recruitment Status : Completed
First Posted : March 13, 2008
Results First Posted : January 28, 2014
Last Update Posted : May 18, 2015
Sponsor:
Information provided by (Responsible Party):
Shire

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gaucher Disease, Type 1
Intervention Biological: VPRIV®
Enrollment 95

Recruitment Details The first participant was enrolled in the study on 13 March 2008 and the last participant completed study procedures on 28 December 2012.
Pre-assignment Details 2 participants who did not have type 1 Gaucher disease were withdrawn from the intent-to-treat (ITT) set as per the statistical analysis plan and removed from the long-term efficacy analyses in this study, needed to support the interpretation of the long-term efficacy results. Hence, 93 of 95 participants were included in the HGT-GCB-044 ITT set.
Arm/Group Title VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg) -TKT032) VPRIV 60 U/kg (Parent Study- VPRIV (60 U/kg)-TKT032) VPRIV 60 U/kg (Parent Study- VPRIV (60U/kg) HGT-GCB-039) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg)HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV(15-60 U/kg)TKT034)
Hide Arm/Group Description VPRIV 45 U/kg, IV, every other week (EOW) for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044 VPRIV 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) VPRIV 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631) imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)and switched 60 U/kg VPRIV in HGT-GCB-044 VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647) and continued in HGT-GCB-044 at the same dose as prescribed in TKT034
Period Title: Overall Study
Started 13 [1] 12 [2] 16 16 38
Completed 1 6 5 7 30
Not Completed 12 6 11 9 8
Reason Not Completed
Refusal Of Required DiagnosticEvaluation             0             0             1             0             0
Death             0             0             0             1             0
Termination Of Study By Sponsor             12             6             10             6             6
Withdrawal Of Consent             0             0             0             2             2
[1]
12 participants were considered ITT population as 1 participant did not have type 1 Gaucher disease
[2]
11 participants were considered ITT population as 1 participant did not have type 1 Gaucher disease
Arm/Group Title VPRIV 60 U/kg (Parent Study VPRIV (45 U/kg)-TKT032) VPRIV 60 U/kg (Parent Study VPRIV (60 U/kg)-TKT032) VPRIV 60 U/kg (Parent Study VPRIV (60U/kg) HGT-GCB-039) VPRIV 60 U/kg (Parent Study-imiglucerase (60 U/kg) HGT-GCB-039 VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034) Total
Hide Arm/Group Description VPRIV 45 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044. VPRIV 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625). VPRIV 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631). Imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631) and switched 60 U/kg VPRIV in HGT-GCB-044 VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647). Participants continued to receive VPRIV at a dose of 15-60 U/kg throughout participation in HGT-GCB-044 Total of all reporting groups
Overall Number of Baseline Participants 12 11 16 16 38 93
Hide Baseline Analysis Population Description
Two participants who did not have type 1 Gaucher disease were withdrawn from the ITT study as per SAP definition and removed from the long-term efficacy analyses in this study, needed to support the interpretation of the long-term efficacy results. Therefore, 93 of 95 (97.9%) participants were included in the HGT-GCB-044 ITT population.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 12 participants 11 participants 16 participants 16 participants 38 participants 93 participants
32.5  (16.75) 22  (11.08) 32.9  (16.14) 25  (17.33) 34.3  (17.94) 31.4  (17.15)
[1]
Measure Description: Age at the time the informed consent was obtained in the core study.
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 16 participants 16 participants 38 participants 93 participants
At least 18 years 2 3 3 5 9 22
Between 18 and 65 years 10 8 13 11 26 68
Greater than or equal to 65 years 0 0 0 0 3 3
[1]
Measure Description: Age at the time the informed consent was obtained in the core study.
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 16 participants 16 participants 38 participants 93 participants
Female
7
  58.3%
6
  54.5%
8
  50.0%
7
  43.8%
18
  47.4%
46
  49.5%
Male
5
  41.7%
5
  45.5%
8
  50.0%
9
  56.3%
20
  52.6%
47
  50.5%
Splenectomy status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 11 participants 16 participants 16 participants 38 participants 93 participants
Yes 0 0 9 10 3 22
No 12 11 7 6 35 71
Baseline hemoglobin concentration per treatment group   [1] 
Mean (Full Range)
Unit of measure:  Gram per deciliter
Number Analyzed 12 participants 11 participants 16 participants 16 participants 38 participants 93 participants
10.68
(8.5 to 12.9)
10.68
(7.1 to 12.3)
11.56
(9.7 to 14.4)
10.58
(8.1 to 13.1)
13.82
(10.7 to 16.5)
12.09
(7.1 to 16.5)
[1]
Measure Description: Baseline was defined as data collected prior to the first dose in the core study (TKT032, TKT034, and HGT-GCB-039).
Baseline platelet counts per treatment group   [1] 
Mean (Full Range)
Unit of measure:  x10^9/L
Number Analyzed 12 participants 11 participants 16 participants 16 participants 38 participants 93 participants
69.3
(13 to 146)
79.4
(47 to 139)
160.1
(44 to 310)
186.3
(63 to 430)
165.4
(29 to 399)
144.81
(13 to 430)
[1]
Measure Description: Baseline was defined as data collected prior to the first dose in the core study (TKT032, TKT034, and HGT-GCB-039).
Baseline liver volume per treatment group   [1] 
Mean (Full Range)
Unit of measure:  Percent (%) body weight
Number Analyzed 12 participants 11 participants 16 participants 16 participants 38 participants 93 participants
1.64
(1.1 to 2.9)
1.63
(1 to 3.2)
1.59
(0.8 to 2.2)
1.68
(0.7 to 2.8)
0.82
(0.6 to 1.3)
1.302
(0.6 to 3.2)
[1]
Measure Description: Baseline was defined as data collected prior to the first dose in the core study (TKT032, TKT034, and HGT-GCB-039). Normal liver volume was defined as 2.5 percent of body weight.
Baseline Spleen volume per treatment group   [1] 
Mean (Full Range)
Unit of measure:  Multiple of Normal
Number Analyzed 12 participants 11 participants 16 participants 16 participants 38 participants 93 participants
23.08
(4.8 to 65.1)
18.48
(5.7 to 36.9)
12.69
(7.2 to 31.6)
23.52
(3.1 to 44.4)
4.1
(1.2 to 15.8)
13.07
(1.2 to 65.1)
[1]
Measure Description: Baseline was defined as data collected prior to the first dose in the core study (TKT032, TKT034, and HT-GCB-039). Normal spleen volume is defined as 0.2 percentage of body weight.
1.Primary Outcome
Title Overall Summary of Treatment Emergent Adverse Events
Hide Description Safety was evaluated by an analysis of adverse events (AEs), concomitant medication use, clinical laboratory tests, vital signs during the infusion of study drug, physical examination, and the development of anti-velaglucerase alfa. No formal comparisons or statistical tests were applied for the safety analyses, including for differences between the groups.
Time Frame Baseline to termination of study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion (full or partial) of study drug were evaluated for safety (ie, were included in the safety population). There were 95 participants in the safety population.
Arm/Group Title VPRIV 60 U/kg(Parent Study VPRIV(45 or 60 U/kg) TKT032,GCB039) VPRIV 60 U/kg (Parent Study-imiglucerase (60 U/kg)HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034)
Hide Arm/Group Description:

This is the overall velaglucerase alfa group consisting of the following population:

VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)

imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)and switched to 60 U/kg VPRIV in HGT-GCB-044
VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647). Participants continued to receive VPRIV at a dose of 15-60 U/kg throughout participation in HGT-GCB-044
Overall Number of Participants Analyzed 41 16 38
Measure Type: Number
Unit of Measure: Participants
Experienced no AEs 3 1 3
Experienced at least 1 AE 38 15 35
Experienced at least 1 drug-related AE 9 7 8
Experienced at least 1 infusion-related AE 5 1 5
Experienced at least 1 severe AE 4 3 4
Experienced at least 1 drug-related severe AE 0 0 0
Experienced at least 1 Life-threatening AE 0 0 0
Experienced at least 1 drug-related Life-threateni 0 0 0
Experienced at least 1 serious AE 6 4 6
Experienced at least 1 drug-related serious AE 0 0 0
Discontinued due to an AE 0 0 0
Deaths 0 1 0
2.Secondary Outcome
Title Change From Baseline to 24 Months in Hemoglobin Concentration for Each Treatment Group
Hide Description [Not Specified]
Time Frame Baseline to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034)
Hide Arm/Group Description:

This arm is the Overall velaglucerase alfa (VPRIV) 60 U/kg and includes participants from the following groups:

VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)

imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)and switched to 60 U/kg VPRIV in HGT-GCB-044
VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647). Participants continued to receive VPRIV at a dose of 15-60 U/kg throughout participation in HGT-GCB-044
Overall Number of Participants Analyzed 39 16 38
Mean (95% Confidence Interval)
Unit of Measure: (g/dL)
2.75
(2.28 to 3.22)
2.00
(1.25 to 2.75)
-0.05
(-0.34 to 0.25)
3.Secondary Outcome
Title Change From Baseline to 24 Months in Platelet Counts for Each Treatment Group
Hide Description [Not Specified]
Time Frame Baseline to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034)
Hide Arm/Group Description:

This arm is the Overall velaglucerase alfa (VPRIV) 60 U/kg and includes participants from the following groups:

VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)

imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)and switched to 60 U/kg VPRIV in HGT-GCB-044
VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647). Participants continued to receive VPRIV at a dose of 15-60 U/kg throughout participation in HGT-GCB-044
Overall Number of Participants Analyzed 39 16 38
Mean (95% Confidence Interval)
Unit of Measure: (10^9/L)
87.85
(72.69 to 103.00)
160.94
(117.22 to 204.66)
9.03
(-2.60 to 20.66)
4.Secondary Outcome
Title Change From Baseline to 24 Months in Normalized Liver Volume for Each Treatment Group
Hide Description [Not Specified]
Time Frame Baseline to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034)
Hide Arm/Group Description:

This arm is the Overall velaglucerase alfa (VPRIV) 60 U/kg and includes participants from the following groups:

VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)

imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)and switched to 60 U/kg VPRIV in HGT-GCB-044
VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647). Participants continued to receive VPRIV at a dose of 15-60 U/kg throughout participation in HGT-GCB-044
Overall Number of Participants Analyzed 39 16 38
Mean (95% Confidence Interval)
Unit of Measure: % Body weight
-1.206
(-1.501 to -0.912)
-1.688
(-2.164 to -1.211)
-0.026
(-0.100 to 0.047)
5.Secondary Outcome
Title Percentage Change From Baseline to 24 Months in Normalized Spleen Volume for Each Treatment Group
Hide Description [Not Specified]
Time Frame Baseline to 24 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039) VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034)
Hide Arm/Group Description:

This arm is the Overall velaglucerase alfa (VPRIV) 60 U/kg and includes participants from the following groups:

VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)

imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)and switched to 60 U/kg VPRIV in HGT-GCB-044
VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647). Participants continued to receive VPRIV at a dose of 15-60 U/kg throughout participation in HGT-GCB-044
Overall Number of Participants Analyzed 39 16 38
Mean (95% Confidence Interval)
Unit of Measure: Precent (%) change
-64.49
(-69.26 to -59.73)
-63.82
(-89.65 to -37.98)
-8.04
(-14.00 to -2.08)
Time Frame Treatment Emergent Adverse Events were defined as AEs which occurred on or after the time of the first infusion in HGT-GCB-044, until 30 days after the participant’s last study infusion.
Adverse Event Reporting Description AEs may have been discovered through observation or examination, and questioning of the participant, complaint by the participant, or by an abnormal clinical laboratory value. Severity of AEs was to be assessed by the investigator and recorded on the electronic case report form (eCRF)regardless of the severity or relationship to study drug.
 
Arm/Group Title VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034) VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039)
Hide Arm/Group Description VPRIV 15- 60 U/kg, IV, EOW for 51 weeks in parent study TKT034 (NCT00478647). Participants continued to receive VPRIV at a dose of 15-60 U/kg throughout participation in HGT-GCB-044

This arm is the Overall velaglucerase alfa (VPRIV) 60 U/kg and includes participants from the following groups:

VPRIV 45 U/kg or 60 U/kg, IV, EOW for 51 weeks in parent study TKT032 (NCT00430625) and switched to 60 U/kg in HGT-GCB-044 to maintain blindness or 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631)

imiglucerase 60 U/kg, IV, EOW for 39 weeks in parent study HGT-GCB-039 (NCT00553631) and switched 60 U/kg VPRIV in HGT-GCB-044
All-Cause Mortality
VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034) VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034) VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/38 (15.79%)      6/41 (14.63%)      4/16 (25.00%)    
Blood and lymphatic system disorders       
Splenomegaly  1  1/38 (2.63%)  1 0/41 (0.00%)  0 0/16 (0.00%)  0
Gastrointestinal disorders       
Abdominal hernia  1  1/38 (2.63%)  1 0/41 (0.00%)  0 0/16 (0.00%)  0
Umbilical hernia  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
General disorders       
Non-cardiac chest pain  1  0/38 (0.00%)  0 1/41 (2.44%)  1 0/16 (0.00%)  0
Hepatobiliary disorders       
Cholelithiasis  1  0/38 (0.00%)  0 1/41 (2.44%)  1 1/16 (6.25%)  1
Infections and infestations       
Bronchopneumonia  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Pyelonephritis acute  1  0/38 (0.00%)  0 1/41 (2.44%)  1 0/16 (0.00%)  0
Respiratory tract infection  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Urinary tract infection  1  1/38 (2.63%)  2 0/41 (0.00%)  0 0/16 (0.00%)  0
Injury, poisoning and procedural complications       
Lower limb fracture  1  0/38 (0.00%)  0 1/41 (2.44%)  1 0/16 (0.00%)  0
Post procedural haematoma  1  1/38 (2.63%)  1 0/41 (0.00%)  0 0/16 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/38 (2.63%)  1 1/41 (2.44%)  2 0/16 (0.00%)  0
Lumbar spinal stenosis  1  1/38 (2.63%)  1 0/41 (0.00%)  0 0/16 (0.00%)  0
Osteonecrosis  1  0/38 (0.00%)  0 2/41 (4.88%)  2 2/16 (12.50%)  3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Benign renal neoplasm  1  0/38 (0.00%)  0 1/41 (2.44%)  1 0/16 (0.00%)  0
Nervous system disorders       
Convulsion  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Syncope  1  1/38 (2.63%)  1 0/41 (0.00%)  0 0/16 (0.00%)  0
Pregnancy, puerperium and perinatal conditions       
Abortion  1  0/38 (0.00%)  0 1/41 (2.44%)  1 0/16 (0.00%)  0
Oligohydramnios  1  1/38 (2.63%)  1 0/41 (0.00%)  0 0/16 (0.00%)  0
Renal and urinary disorders       
Renal colic  1  0/38 (0.00%)  0 1/41 (2.44%)  1 0/16 (0.00%)  0
Vascular disorders       
Phlebitis  1  1/38 (2.63%)  1 0/41 (0.00%)  0 0/16 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
VPRIV 15-60 U/kg (Parent Study VPRIV (15-60 U/kg) TKT034) VPRIV 60 U/kg(VPRIV Parent Study 45 or 60 U/kg- TKT032,GCB039) VPRIV 60 U/kg (Parent Study-imiglucerase(60 U/kg) HGT-GCB-039)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   35/38 (92.11%)      35/41 (85.37%)      15/16 (93.75%)    
Blood and lymphatic system disorders       
Anaemia  1  1/38 (2.63%)  1 0/41 (0.00%)  0 1/16 (6.25%)  2
Leukocytosis  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Lymphadenitis  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Splenomegaly  1  0/38 (0.00%)  0 3/41 (7.32%)  3 0/16 (0.00%)  0
Endocrine disorders       
Hyperprolactinaemia  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Eye disorders       
Conjunctivitis allergic  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  2
Dry eye  1  2/38 (5.26%)  2 0/41 (0.00%)  0 0/16 (0.00%)  0
Visual acuity reduced  1  0/38 (0.00%)  0 1/41 (2.44%)  1 1/16 (6.25%)  1
Gastrointestinal disorders       
Abdominal pain  1  2/38 (5.26%)  2 3/41 (7.32%)  3 1/16 (6.25%)  1
Abdominal pain upper  1  3/38 (7.89%)  4 4/41 (9.76%)  6 2/16 (12.50%)  2
Diarrhoea  1  2/38 (5.26%)  2 2/41 (4.88%)  3 1/16 (6.25%)  1
Dyspepsia  1  2/38 (5.26%)  4 3/41 (7.32%)  3 0/16 (0.00%)  0
Toothache  1  2/38 (5.26%)  3 6/41 (14.63%)  7 2/16 (12.50%)  2
Rectal haemorrhage  1  1/38 (2.63%)  1 0/41 (0.00%)  0 1/16 (6.25%)  1
Vomiting  1  2/38 (5.26%)  2 1/41 (2.44%)  1 0/16 (0.00%)  0
General disorders       
Fatigue  1  7/38 (18.42%)  8 3/41 (7.32%)  3 0/16 (0.00%)  0
Pyrexia  1  2/38 (5.26%)  2 6/41 (14.63%)  10 1/16 (6.25%)  1
Adverse drug reaction  1  2/38 (5.26%)  2 0/41 (0.00%)  0 0/16 (0.00%)  0
Chest discomfort  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Gait disturbance  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Influenza like illness  1  2/38 (5.26%)  3 0/41 (0.00%)  0 0/16 (0.00%)  0
Hepatobiliary disorders       
Biliary colic  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  2
Cytolytic hepatitis  1  0/38 (0.00%)  0 3/41 (7.32%)  6 0/16 (0.00%)  0
Cholelithiasis  1  0/38 (0.00%)  0 0/41 (0.00%)  0 2/16 (12.50%)  2
Liver disorder  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Infections and infestations       
Bronchitis  1  1/38 (2.63%)  1 5/41 (12.20%)  13 1/16 (6.25%)  1
Bronchitis acute  1  0/38 (0.00%)  0 5/41 (12.20%)  5 1/16 (6.25%)  1
Gastroenteritis  1  2/38 (5.26%)  2 7/41 (17.07%)  10 1/16 (6.25%)  1
Influenza  1  4/38 (10.53%)  6 6/41 (14.63%)  10 4/16 (25.00%)  12
Nasopharyngitis  1  16/38 (42.11%)  31 11/41 (26.83%)  20 3/16 (18.75%)  4
Pharyngitis  1  5/38 (13.16%)  11 2/41 (4.88%)  2 1/16 (6.25%)  1
Tinea versicolour  1  0/38 (0.00%)  0 4/41 (9.76%)  13 1/16 (6.25%)  2
Tonsillitis  1  1/38 (2.63%)  1 4/41 (9.76%)  4 0/16 (0.00%)  0
Upper respiratory tract infection  1  9/38 (23.68%)  9 4/41 (9.76%)  7 6/16 (37.50%)  14
Urinary tract infection  1  3/38 (7.89%)  5 3/41 (7.32%)  5 0/16 (0.00%)  0
Dental caries  1  0/38 (0.00%)  0 1/41 (2.44%)  1 1/16 (6.25%)  1
Diarrhoea infectious  1  2/38 (5.26%)  2 0/41 (0.00%)  0 0/16 (0.00%)  0
Hepatitis a  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Hordeolum  1  1/38 (2.63%)  1 2/41 (4.88%)  3 1/16 (6.25%)  1
Lower respiratory tract infection  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Pyelonephritis acute  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Respiratory tract infection  1  1/38 (2.63%)  2 0/41 (0.00%)  0 2/16 (12.50%)  3
Rhinitis  1  0/38 (0.00%)  0 3/41 (7.32%)  3 1/16 (6.25%)  1
Sinusitis  1  3/38 (7.89%)  5 0/41 (0.00%)  0 0/16 (0.00%)  0
Staphylococcal infection  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Vaginal infection  1  3/38 (7.89%)  3 1/41 (2.44%)  1 0/16 (0.00%)  0
Varicella  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Vulvovaginal mycotic infection  1  2/38 (5.26%)  2 1/41 (2.44%)  1 0/16 (0.00%)  0
Injury, poisoning and procedural complications       
Anaemia postoperative  1  0/38 (0.00%)  0 1/41 (2.44%)  1 1/16 (6.25%)  1
Burns first degree  1  0/38 (0.00%)  0 3/41 (7.32%)  5 0/16 (0.00%)  0
Contusion  1  1/38 (2.63%)  2 0/41 (0.00%)  0 1/16 (6.25%)  1
Injury  1  0/38 (0.00%)  0 2/41 (4.88%)  2 1/16 (6.25%)  1
Excoriation  1  1/38 (2.63%)  1 0/41 (0.00%)  0 1/16 (6.25%)  1
Joint injury  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Muscle strain  1  2/38 (5.26%)  2 0/41 (0.00%)  0 0/16 (0.00%)  0
Procedural pain  1  3/38 (7.89%)  6 0/41 (0.00%)  0 0/16 (0.00%)  0
Skin laceration  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Investigations       
Alanine aminotransferase increased  1  2/38 (5.26%)  2 0/41 (0.00%)  0 1/16 (6.25%)  1
Aspartate aminotransferase Increased  1  1/38 (2.63%)  1 0/41 (0.00%)  0 1/16 (6.25%)  1
Blood creatine phosphokinase Increased  1  2/38 (5.26%)  2 1/41 (2.44%)  3 0/16 (0.00%)  0
Blood urine present  1  0/38 (0.00%)  0 1/41 (2.44%)  1 1/16 (6.25%)  1
Haemoglobin decreased  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Mean cell volume increased  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Red blood cell count decreased  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Neutrophil count increased  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Red blood cells urine positive  1  0/38 (0.00%)  0 1/41 (2.44%)  1 1/16 (6.25%)  1
White blood cell count increased  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
White blood cells urine positive  1  2/38 (5.26%)  2 0/41 (0.00%)  0 1/16 (6.25%)  1
Musculoskeletal and connective tissue disorders       
Arthralgia  1  9/38 (23.68%)  13 14/41 (34.15%)  33 2/16 (12.50%)  34
Back pain  1  4/38 (10.53%)  7 5/41 (12.20%)  6 1/16 (6.25%)  1
Bone pain  1  7/38 (18.42%)  12 7/41 (17.07%)  20 2/16 (12.50%)  7
Myalgia  1  2/38 (5.26%)  3 3/41 (7.32%)  3 0/16 (0.00%)  0
Pain in extremity  1  4/38 (10.53%)  6 5/41 (12.20%)  6 1/16 (6.25%)  1
Shoulder pain  1  3/38 (7.89%)  4 2/41 (4.88%)  4 1/16 (6.25%)  2
Arthritis  1  1/38 (2.63%)  1 0/41 (0.00%)  0 2/16 (12.50%)  2
Muscle spasms  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Osteoarthritis  1  3/38 (7.89%)  3 1/41 (2.44%)  1 0/16 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Lentigo  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Nervous system disorders       
Headache  1  6/38 (15.79%)  10 7/41 (17.07%)  16 4/16 (25.00%)  6
Paraesthesia  1  2/38 (5.26%)  2 2/41 (4.88%)  2 1/16 (6.25%)  3
Convulsion  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Dizziness  1  0/38 (0.00%)  0 3/41 (7.32%)  3 1/16 (6.25%)  3
Drop attacks  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Hypoaesthesia  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Sciatica  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Renal and urinary disorders       
Nephrolithiasis  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Reproductive system and breast disorders       
Galactorrhoea  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Respiratory, thoracic and mediastinal disorders       
Cough  1  5/38 (13.16%)  6 0/41 (0.00%)  0 3/16 (18.75%)  4
Pharyngolaryngeal pain  1  5/38 (13.16%)  8 3/41 (7.32%)  4 0/16 (0.00%)  0
Epistaxis  1  1/38 (2.63%)  2 0/41 (0.00%)  0 1/16 (6.25%)  1
Dysphonia  1  2/38 (5.26%)  2 0/41 (0.00%)  0 0/16 (0.00%)  0
Dyspnoea  1  1/38 (2.63%)  2 0/41 (0.00%)  0 1/16 (6.25%)  3
Postnasal drip  1  2/38 (5.26%)  2 0/41 (0.00%)  0 0/16 (0.00%)  0
Productive cough  1  0/38 (0.00%)  0 4/41 (9.76%)  5 0/16 (0.00%)  0
Rhinitis allergic  1  0/38 (0.00%)  0 1/41 (2.44%)  1 1/16 (6.25%)  3
Sinus congestion  1  3/38 (7.89%)  3 0/41 (0.00%)  0 0/16 (0.00%)  0
Tachypnoea  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  2
Skin and subcutaneous tissue disorders       
Dermatitis allergic  1  2/38 (5.26%)  2 0/41 (0.00%)  0 0/16 (0.00%)  0
Dermatitis contact  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Rash vesicular  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  7
Erythema  1  0/38 (0.00%)  0 0/41 (0.00%)  0 1/16 (6.25%)  1
Pruritus generalised  1  1/38 (2.63%)  1 0/41 (0.00%)  0 1/16 (6.25%)  1
Vascular disorders       
Hypertension  1  4/38 (10.53%)  6 5/41 (12.20%)  6 0/16 (0.00%)  0
Haematoma  1  2/38 (5.26%)  2 1/41 (2.44%)  1 0/16 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (9.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Shire’s agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤180 days from the time submitted to Shire for review. Shire does not prohibit publication, but can require the removal of confidential information(excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial’s multi-center publication
Results Point of Contact
Name/Title: MedInfo
Organization: Shire
Phone: +1-866-888-0660