Clinical Trial Results:
A Single-arm Uncontrolled 12-month Clinical Study to Evaluate the Safety and Efficacy of
Miglustat (Zavesca®) for the Treatment of Niemann-Pick Disease Type C (NPC) in Chinese Subjects
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Summary
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EudraCT number |
2022-002514-16 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
29 Mar 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
28 Dec 2022
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First version publication date |
28 Dec 2022
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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 |
AC-056C405
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03910621 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Actelion Pharmaceuticals Trading (Shanghai) Co., Ltd
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Sponsor organisation address |
Suite 2002-2003, Henderson 688, No. 688 West Nanjing Road, Shanghai, China, 200041
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Public contact |
Clinical Registry Group, Actelion Pharmaceuticals Trading (Shanghai) Co., Ltd, ClinicalTrialsEU@its.jnj.com
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Scientific contact |
Clinical Registry Group, Actelion Pharmaceuticals Trading (Shanghai) Co., Ltd, ClinicalTrialsEU@its.jnj.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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
29 Mar 2022
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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 |
29 Mar 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main objective of this trial was to evaluate the efficacy of miglustat on the rate of disease progression and disease stabilization in subjects with Niemann-Pick Disease Type C (NPC).
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Protection of trial subjects |
This study was conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with Good Clinical Practices and applicable regulatory requirements.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Apr 2020
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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 |
China: 17
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Worldwide total number of subjects |
17
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EEA total number of subjects |
0
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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) |
5
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Adolescents (12-17 years) |
7
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Adults (18-64 years) |
5
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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 |
- | ||||||||||||
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Pre-assignment
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Screening details |
Out of the 17 enrolled subjects, 14 subjects completed the study. | ||||||||||||
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Period 1
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Period 1 title |
Overall Study (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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Miglustat | ||||||||||||
Arm description |
Adult and pediatric subjects aged 4 years and older, with established diagnosis of niemann-pick disease type C (NPC) were enrolled and recieved miglustat 200 miligrams (mg) from Day 1 through Week 52. Adult subjects received miglustat 200 mg thrice daily (t.i.d), while for subjects with mild renal impairment, the starting dose was 200 mg twice daily (b.i.d) and for moderate renal impairment, the starting dose was 200 mg once daily. For subjects with NPC less than 12 years of age, dosage regimen (0.2 grams [g] t.i.d, 0.2 g b.i.d, 0.1 g t.i.d, 0.1 g b.i.d, and 0.1 g once daily) was adjusted based on body surface area (BSA). | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Miglustat
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Miglustat 200 mg was administered t.i.d from Day 1 through Week 52. The recommended dose was 200 mg t.i.d. and adjusted according to BSA for children less than 12 years of age.
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Baseline characteristics reporting groups
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Reporting group title |
Miglustat
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Reporting group description |
Adult and pediatric subjects aged 4 years and older, with established diagnosis of niemann-pick disease type C (NPC) were enrolled and recieved miglustat 200 miligrams (mg) from Day 1 through Week 52. Adult subjects received miglustat 200 mg thrice daily (t.i.d), while for subjects with mild renal impairment, the starting dose was 200 mg twice daily (b.i.d) and for moderate renal impairment, the starting dose was 200 mg once daily. For subjects with NPC less than 12 years of age, dosage regimen (0.2 grams [g] t.i.d, 0.2 g b.i.d, 0.1 g t.i.d, 0.1 g b.i.d, and 0.1 g once daily) was adjusted based on body surface area (BSA). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Miglustat
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Reporting group description |
Adult and pediatric subjects aged 4 years and older, with established diagnosis of niemann-pick disease type C (NPC) were enrolled and recieved miglustat 200 miligrams (mg) from Day 1 through Week 52. Adult subjects received miglustat 200 mg thrice daily (t.i.d), while for subjects with mild renal impairment, the starting dose was 200 mg twice daily (b.i.d) and for moderate renal impairment, the starting dose was 200 mg once daily. For subjects with NPC less than 12 years of age, dosage regimen (0.2 grams [g] t.i.d, 0.2 g b.i.d, 0.1 g t.i.d, 0.1 g b.i.d, and 0.1 g once daily) was adjusted based on body surface area (BSA). | ||
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End point title |
Change From Baseline to Week 52 in Horizontal Saccadic Eye Movement (HSEM) as Measured by Saccadic Peak Acceleration [1] | ||||||||
End point description |
Change from baseline to Week 52 in HSEM as measured by saccadic peak acceleration was reported. Saccadic eye movements (SEM) were rapid eye movements under voluntary control (including saccade initiation, speed and extent) that were essential for the normal shifting of focus from one object to another within the visual field. Full analysis set included all enrolled subjects who completed the screening period. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline to Week 52
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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: No inferential statistics was planned for this primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline to Week 52 in HSEM as Measured by Mean Velocity [2] | ||||||||
End point description |
Change from baseline to Week 52 in HSEM as measured by mean velocity was reported. SEM were rapid eye movements under voluntary control (including saccade initiation, speed and extent) that were essential for the normal shifting of focus from one object to another within the visual field. Full analysis set included all enrolled subjects who completed the screening period. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline to Week 52
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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: No inferential statistics was planned for this primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline to Week 52 in HSEM as Measured by Peak Duration [3] | ||||||||
End point description |
Change from baseline to Week 52 in HSEM as measured by peak duration was reported. SEM were rapid eye movements under voluntary control (including saccade initiation, speed and extent) that were essential for the normal shifting of focus from one object to another within the visual field. Full analysis set included all enrolled subjects who completed the screening period. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline to Week 52
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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: No inferential statistics was planned for this primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline to Week 52 in HSEM as Measured by Linear Regression Slopes [4] | ||||||||
End point description |
Change from baseline to Week 52 in HSEM as measured by linear regression slopes was reported. SEM were rapid eye movements under voluntary control (including saccade initiation, speed and extent) that were essential for the normal shifting of focus from one object to another within the visual field. Full analysis set included all enrolled subjects who completed the screening period. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline to Week 52
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| Notes [4] - 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: No inferential statistics was planned for this primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline to Week 52 in HSEM as Measured by Line Slopes [5] | ||||||||
End point description |
Change from baseline to Week 52 in HSEM as measured by line slopes was reported. SEM were rapid eye movements under voluntary control (including saccade initiation, speed and extent) that were essential for the normal shifting of focus from one object to another within the visual field. Full analysis set included all enrolled subjects who completed the screening period. Here, 'N' (number of subjects analysed) signifies number of subjects who were evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Baseline to Week 52
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| Notes [5] - 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: No inferential statistics was planned for this primary endpoint. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Change From Baseline to Week 26 and Week 52 in Pineda Disability Scale Score | ||||||||||||||||||||||||||||||||
End point description |
Change form baseline to Week 26 and Week 52 in pineda disability scale score was reported. The changes in Pineda disability scale was a total additive score of 6 items which included ambulation ranged from 1(clumsy)-5(wheelchair-bound), manipulation ranged from 1(tremor)-4(severe dysmetria/dystonia), language ranged from 1(delayed acquisitions)-5(absence of communication), swallowing ranged from 1(abnormal chewing)-4(nasogastric/gastric button feeding), seizures ranged from 1(occasional seizures)-3(seizures resistant to antiepileptic drugs), and ocular movements ranged from 1(slow ocular pursuit)-3(complete ophthalmoplegia). The total score ranged from 0-24, where higher score indicates poorer condition. Full analysis set included all enrolled subjects who completed the screening period. Here, 'N'(number of subjects analysed) signifies number of subjects who were evaluable for this endpoint and 'n'(number analysed) signifies number of subjects evaluable at the specified timepoints.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26, and Week 52
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||
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End point title |
Number of Subjects with Treatment-emergent Adverse Events (TEAEs) | ||||||
End point description |
An AE was any untoward medical occurrence, that was, any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs in a subject during the course of the study, whether or not considered by the investigator as related to study treatment. TEAE was any AE temporally associated with the use of study treatment (from study treatment initiation until 30 days after study treatment discontinuation) whether or not considered by the investigator as related to study treatment. The safety set (SS) included all subjects who received at least one dose of miglustat.
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End point type |
Secondary
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End point timeframe |
Up to Week 52
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Subjects with Treatment-emergent Serious Adverse Events (TESAEs) | ||||||
End point description |
A SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. An AE is any untoward medical occurrence, i.e., any unfavorable and unintended sign, including an abnormal laboratory finding, symptom, or disease that occurs in a subject during the course of the study, whether or not considered by the investigator as related to study treatment. Treatment-emergent SAEs are defined as serious events between administration of study drug and after the last dose that were absent before treatment or that worsen relative to pretreatment state. The safety set (SS) included all subjects who received at least one dose of miglustat.
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End point type |
Secondary
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End point timeframe |
Up to Week 52
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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 |
Up to 52 weeks for serious and other (non-serious) adverse events and up to 56 weeks for all-cause mortality
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Adverse event reporting additional description |
The safety set (SS) included all subjects who received at least one dose of miglustat.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
19.0
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Reporting groups
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Reporting group title |
Miglustat
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Reporting group description |
Adult and pediatric subjects aged 4 years and older, with established diagnosis of niemann-pick disease type C (NPC) were enrolled and recieved miglustat 200 miligrams (mg) from Day 1 through Week 52. Adult subjects received miglustat 200 mg thrice daily (t.i.d), while for subjects with mild renal impairment, the starting dose was 200 mg twice daily (b.i.d) and for moderate renal impairment, the starting dose was 200 mg once daily. For subjects with NPC less than 12 years of age, dosage regimen (0.2 grams [g] t.i.d, 0.2 g b.i.d, 0.1 g t.i.d, 0.1 g b.i.d, and 0.1 g once daily) was adjusted based on body surface area (BSA). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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25 Mar 2020 |
The purpose of this amendment was to add an additional choice of laboratory for genetic test that confirms the Niemann-Pick Disease Type C (NPC) disease diagnosis. |
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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. | |||
| None reported | |||
