Clinical Trial Results:
A Cross-sectional Study of Renal Function in Treatment-naïve, Young Male Patients with Fabry Disease
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Summary
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EudraCT number |
2012-001966-14 |
Trial protocol |
ES |
Global end of trial date |
17 Aug 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
02 Mar 2017
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First version publication date |
02 Mar 2017
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
AGAL19110
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01839526 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Genzyme Corporation
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Sponsor organisation address |
500 Kendall Street, Cambridge, MA, United States, 02142
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Public contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Scientific contact |
Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Nov 2016
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Aug 2016
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To document renal function and other Fabry disease manifestations across age in treatment-naïve, young male subjects with Fabry disease.
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Protection of trial subjects |
The study was conducted by investigators experienced in the treatment of pediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
13 May 2013
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Argentina: 3
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
Austria: 1
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Country: Number of subjects enrolled |
Brazil: 2
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Country: Number of subjects enrolled |
Spain: 4
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Country: Number of subjects enrolled |
United Kingdom: 3
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Country: Number of subjects enrolled |
Canada: 3
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Country: Number of subjects enrolled |
Finland: 1
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Country: Number of subjects enrolled |
France: 3
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Country: Number of subjects enrolled |
Hungary: 1
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Country: Number of subjects enrolled |
Norway: 4
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Country: Number of subjects enrolled |
Poland: 5
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Country: Number of subjects enrolled |
United States: 8
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Worldwide total number of subjects |
39
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EEA total number of subjects |
23
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
16
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Adolescents (12-17 years) |
12
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Adults (18-64 years) |
11
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study was conducted at 19 centers in 13 countries between 13 May 2013 and 17 August 2016. A total of 45 subjects were screened, of whom 6 were screen failures. Screen failures were due to failure to meet inclusion criteria. | ||||||
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Pre-assignment
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Screening details |
Out of 45 screened subjects, 39 subjects were enrolled in the study. | ||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Fabry Disease - All Subjects | ||||||
Arm description |
All male subjects, with Fabry disease and who had not received any interventional treatment for the disease within 30 days of screening. They were observed in this cross-sectional study. | ||||||
Arm type |
No intervention | ||||||
Investigational medicinal product name |
Non interventional medicinal product (NIMP): Iohexol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Small dose of iohexol was administered for determining glomerular filtration rate (GFR).
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Baseline characteristics reporting groups
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Reporting group title |
Overall Period
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Reporting group description |
All male subjects, with Fabry disease and who had not received any interventional treatment for the disease within 30 days of screening. They were observed in this cross-sectional study. | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Fabry Disease - All Subjects
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Reporting group description |
All male subjects, with Fabry disease and who had not received any interventional treatment for the disease within 30 days of screening. They were observed in this cross-sectional study. | ||
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End point title |
Fabry Disease Parameter: GFR Estimated from Serum Creatinine (eGFR) [1] | ||||||||||||
End point description |
GFR was assessed by estimation from serum creatinine level (eGFR) using an age-appropriate method based on the subject's age at the screening visit (for the purpose of determining a subject’s eligibility for measurement of iohexol glomerular filtration rate [iGFR]) and at the clinical investigational visit (for use in statistical analyses). For subjects <18 years old, the Bedside Schwartz equation was used to calculate eGFR, while for subjects >18 years old, the CKD-EPI equation was used. Analysis was performed on safety population which included all subjects who signed the informed consent and deemed eligible to enroll based on screening assessments. Number of subjects analyzed = subjects with available data for this point. Here, 'n' signifies number of subjects with available data for specified category.
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End point type |
Primary
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End point timeframe |
Screening, Day 1
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Fabry Disease Parameter: Glomerular Filtration Rate (GFR) Measured Using Plasma Iohexol Clearance (iGFR) [2] | ||||||||
End point description |
GFR was calculated by plasma iohexol clearance after the required medication washout. Analysis was performed on safety population. Number of subjects analyzed = subjects with available data for this endpoint.
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End point type |
Primary
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End point timeframe |
Day 1 onwards up to safety follow-up phone contact (up to Day 28)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Fabry Disease Parameter: Protein Excretion Assessed from Three First-Morning Urine Voids [3] | ||||||||||||||||||||||
End point description |
Protein excretion was evaluated from the 3 first morning urine voids, each obtained at least 1 week apart and not more than 2 weeks apart. Mean value for each parameter was calculated and reported. Parameters determined for each urine sample were albumin; total protein; creatinine (for calculation of albumin:creatinine ratio [ACR] and protein-creatinine ratio [PCR]); retinol binding protein (RBP); and Beta-2 microglobulin. Analysis was performed on safety population. Number of subjects analyzed = subjects with available data for this endpoint.
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End point type |
Primary
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End point timeframe |
Day 1 after the medication washout up to follow-up phone contact (Day28)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: As the endpoint is descriptive in nature, no statistical analysis is provided. |
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Fabry Disease Parameter: Electrocardiogram (ECG) Parameters | ||||||||||||||||||||||
End point description |
ECG parameters included heart rate, PR interval, QRS interval, QT interval, RR interval, QTcB interval and QTcF interval. PR interval is the time on ECG tracing from the start of the P wave to the start of the R wave. PR interval represents the time from the onset of atrial depolarization until the onset of ventricular depolarization. QRS interval is the time from the start of the Q wave to the end of S wave. QRS interval represents depolarization of the ventricular myocardium. QT interval is a measure of the time between the start of the Q wave and the end of the T wave and represents electrical depolarization and repolarization of the ventricles. The QTcB includes a Bazett’s correction factor for changes in heart rate and QTcF includes a Fredericia’s correction factor for changes in heart rate. The RR interval is the time between QRS complexes. Analysis was performed on safety population. Number of subjects analyzed = subjects with available data for this endpoint.
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End point type |
Secondary
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End point timeframe |
Day 1 onwards up to safety follow-up phone contact (up to Day 28)
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| No statistical analyses for this end point | |||||||||||||||||||||||
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End point title |
Fabry Disease Parameter: Number of Subjects with Clinically Significant Echocardiogram Findings | ||||||||||||
End point description |
Analysis was performed on safety population.
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End point type |
Secondary
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End point timeframe |
Day 1 onwards up to safety follow-up phone contact (up to Day 28)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Fabry Disease Parameter: Number of Subjects with Gastrointestinal (GI) Symptoms at Screening | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
GI symptoms were collected at the screening visit by asking the subject-specific questions about the following GI symptoms: abdominal pain; diarrhea; nausea; vomiting (subjects who answered "yes" were reported); maximum number of bowel movements per day in the past week; stool consistency on average in the past week; severity of abdominal pain on average in the past week; severity of bloating on average in the past week. Analysis was performed on safety population.
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End point type |
Secondary
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End point timeframe |
At screening
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End point title |
Fabry Disease Parameter: Quality of Life assessed by Pediatric Pain Questionnaire (PedsQL) Scores | ||||||||||||
End point description |
PedsQL completed by subjects between 5 and 17 years of age. It comprises of 2 questions:‘How do you feel now’ and ‘Worst pain this week’, each measured on a 0-10 cm VAS scale (0=no pain; 10=severe pain). Analysis was performed on safety population. Number of subjects analyzed = subjects with available data for this endpoint.
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End point type |
Secondary
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End point timeframe |
At screening
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Fabry Disease Parameter: Quality of Life assessed by Brief Pain Inventory Short Form (BPI [SF]) Scores | ||||||||||||
End point description |
BPI [SF] was completed by subjects >=18 years of age. BPI (SF) comprises of 2 dimensions of pain: severity/intensity (4 items: worst, least, average and now pain) and interference with daily function (7 items: pain interference with general activity, walking, work, mood, enjoyment of life, relations with others and sleep). Each item was rated by subject on a scale ranges from 0-10, where lower scores indicated less pain. In this endpoint, average pain reported by subjects in last 24 hours along with the mean pain interference was reported. Analysis was performed on safety population. Number of subjects analyzed=subjects with available data for this endpoint.
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End point type |
Secondary
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End point timeframe |
At screening
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Fabry Disease Parameter: Plasma Globotriaosylceramide (GL-3) Concentrations | ||||||||||||
End point description |
Accumulation of Globotriaosylceramide in blood was evaluated by measuring levels of total GL-3 and lyso-GL-3 using tandem mass spectrometry. Blood samples were collected for all subjects and obtained either before or after the medication washout. Analysis was performed on safety population.
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End point type |
Secondary
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End point timeframe |
Day 1 onwards up to safety follow-up phone contact (up to Day 28)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Fabry Disease Parameter: Urine Globotriaosylceramide (GL-3) Concentrations | ||||||||||||
End point description |
Accumulation of Globotriaosylceramide concentration in urine was evaluated by measuring levels of total GL-3 and lyso-GL-3 using tandem mass spectrometry. Urine samples were obtained either before or after the medication washout. Analysis was performed on safety population.
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End point type |
Secondary
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End point timeframe |
Day 1 up to Day 28 (Before or after the medication washout)
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
All Adverse Events (AE) were collected from signature of the informed consent form up to the final visit (Day 28) regardless of seriousness or relationship to investigational product.
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Adverse event reporting additional description |
AEs in the study subject population would be expected to be related to Fabry or concomitant diseases, or related to procedures (i.e., iohexol). All subjects were observed for approximately 4 weeks after iohexol administration. All AEs from the time of written informed consent through completion of the safety follow-up phone contact were reported.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
ed 19.0
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Reporting groups
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Reporting group title |
All Subjects: Age range (5 to <12 years)
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Reporting group description |
All male subjects in the age range of 5 to <12 years, with Fabry disease and who had not received any interventional treatment for the disease within 30 days of screening. They were observed in this cross-sectional study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
All Subjects: Age range (>=18 years)
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Reporting group description |
All male subjects in the age of >=18 years, with Fabry disease and who had not received any interventional treatment for the disease within 30 days of screening. They were observed in this cross-sectional study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
All Subjects: Age range (12 to <18 years)
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Reporting group description |
All male subjects in the age range of 12 to <18 years, with Fabry disease and who had not received any interventional treatment for the disease within 30 days of screening. They were observed in this cross-sectional study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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23 Apr 2012 |
-Clarified that both a medical/surgical history and a Fabry specific history was required in the subjects. -Added a physical examination at the clinical investigation visit and clarified that the physical examination at screening include an assessment of angiokeratomas and Tanner stage. -Added respiratory rate and temperature to the vital signs assessment. -Clarified that laboratory samples were collected at the screening visit. -Added a table describing the Tanner Stages for reference. -Reflected changes in company ownership, study team changes and department name changes. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Enrollment period not extended and screening stopped for slow recruitment and in accordance with provisions of the protocol. Not linked to any safety concern. | |||
