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Clinical Trial Results:
An Open-Label Extension Study of Patients with Late-Onset Pompe Disease Who Were Previously Enrolled in Protocol AGLU02704

Summary
EudraCT number	2006-003644-31
Trial protocol	FR NL DE
Global end of trial date	13 Nov 2008

Results information
Results version number	v1(current)
This version publication date	23 May 2016
First version publication date	12 Jun 2015
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

AGLU03206

ISRCTN number

US NCT number

NCT00455195

WHO universal trial number (UTN)

Sponsor organisation name

Genzyme Corporation

Sponsor organisation address

500 Kendall Street, Cambridge, MA, United States, 02142

Public contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Scientific contact

Trial Transparency Team, Sanofi aventis recherche & développement, Contact-US@sanofi.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

12 Feb 2009

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

13 Nov 2008

Was the trial ended prematurely?

Main objective of the trial

The objective of this extension study is to assess the long-term safety and efficacy of Myozyme treatment in subjects with Late-Onset Pompe Disease who were previously treated under the placebo-controlled, double-blind study AGLU02704. The primary objectives of the study are: 1) to evaluate the safety profile of Myozyme; 2) to determine the effect of Myozyme treatment on functional endurance as measured by the Six Minute Walk Test (6MWT); and 3) to determine the effect of Myozyme treatment on respiratory muscle weakness as measured by Forced Vital Capacity (FVC) in the upright position.

Protection of trial subjects

Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.

Background therapy

Evidence for comparator

Actual start date of recruitment

23 Mar 2007

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Netherlands: 22

Country: Number of subjects enrolled

France: 10

Country: Number of subjects enrolled

United States: 58

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

81 of the 90 subjects enrolled in the double-blind placebo controlled AGLU02704 (NCT00158600) study continued on to the open-label extension study AGLU03206.

Period 1 title

Double-blind Study AGLU02704

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Alglucosidase Alfa/Alglucosidase Alfa

Arm description

Subjects who received alglucosidase alfa during the double-blind study AGLU02704 (NCT00158600) and, if they completed the double blind study, continued alglucosidase alfa in the extension study. Both study experiences on alglucosidase alfa are represented within AGLU03206.

Arm type

Experimental

Investigational medicinal product name

Alglucosidase alfa

Investigational medicinal product code

Other name

Myozyme, Lumizyme

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

20 mg/kg every other week (qow) until their participation in both the AGLU02704 (NCT00158600) and AGLU03206 studies combined equaled a minimum of 104 weeks.

Placebo/Alglucosidase Alfa

Arm description

Subjects who received placebo during the double-blind study AGLU02704 (NCT00158600), completed the double-blind study, and started alglucosidase alfa in the extension study. Only subjects' experience on alglucosidase alfa in the extension study is represented.

Arm type

Experimental

Investigational medicinal product name

Alglucosidase alfa

Investigational medicinal product code

Other name

Myozyme, Lumizyme

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

20 mg/kg every other week (qow) for up to 52 weeks. Only the alglucosidase alfa treatment experience is included in this extension study.

Number of subjects in period 1	Alglucosidase Alfa/Alglucosidase Alfa	Placebo/Alglucosidase Alfa
Started	60	30
Completed	55	26
Not completed	5	4
Adverse Event	2	1
Death	1	-
Withdrawal by Subject	2	2
Unable to commit time to study	-	1

Period 2 title

Extension Study AGLU03206

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Alglucosidase Alfa/Alglucosidase Alfa

Arm description

Arm type

Experimental

Investigational medicinal product name

Alglucosidase alfa

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

20 mg/kg every other week (qow) until their participation in both the AGLU02704 (NCT00158600) and AGLU03206 studies combined equaled a minimum of 104 weeks.

Placebo/Alglucosidase Alfa

Arm description

Arm type

Experimental

Investigational medicinal product name

Alglucosidase alfa

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

20 mg/kg every other week (qow) for up to 52 weeks. Only the alglucosidase alfa treatment experience is included in this extension study.

Number of subjects in period 2	Alglucosidase Alfa/Alglucosidase Alfa	Placebo/Alglucosidase Alfa
Started	55	26
Completed	55	26

Baseline characteristics

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Reporting group title

Alglucosidase Alfa/Alglucosidase Alfa

Reporting group description

Reporting group title

Placebo/Alglucosidase Alfa

Reporting group description

Reporting group values	Alglucosidase Alfa/Alglucosidase Alfa	Placebo/Alglucosidase Alfa	Total
Number of subjects	60	30	90
Age categorical
Units: Subjects
Age continuous
Age at first infusion of alglucosidase alfa. The Alglucosidase Alfa/Alglucosidase Alfa treatment arm includes sujects' study experience in the double-blind study (AGLU02704 (NCT00158600)) and the extension study (AGLU03206 (NCT00455195) hence 60 subjects are represented. The Placebo/Alglucosidase Alfa treatment arm includes subjects' study experience on Alglucosidase Alfa in the extension study (AGLU03206) hence 26 subjects are represented.
Units: years
arithmetic mean (standard deviation)	45.3 ± 12.37	46.8 ± 8.62	-
Gender categorical
Units: Subjects
Female	26	15	41
Male	34	11	45
Data not available	0	4	4
Race/Ethnicity
The Alglucosidase Alfa/Alglucosidase Alfa treatment arm includes subjects' study experience in the double-blind study (AGLU02704 (NCT00158600)) and the extension study (AGLU03206 (NCT00455195) hence 60 subjects are represented. The Placebo/Alglucosidase Alfa treatment arm includes subjects' study experience on Alglucosidase Alfa in the extension study (AGLU03206) hence 26 subjects are represented.
Units: Subjects
Hispanic	1	1	2
Asian	1	0	1
Black or African American	0	0	0
White	57	24	81
Unknown or Not Reported	1	1	2
Data not available	0	4	4

End points

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Reporting group title

Alglucosidase Alfa/Alglucosidase Alfa

Reporting group description

Reporting group title

Placebo/Alglucosidase Alfa

Reporting group description

Reporting group title

Alglucosidase Alfa/Alglucosidase Alfa

Reporting group description

Reporting group title

Placebo/Alglucosidase Alfa

Reporting group description

Primary: Summary of Subjects Reporting Treatment-Emergent Adverse Events For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

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End point title

Summary of Subjects Reporting Treatment-Emergent Adverse Events For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) ^[1] ^[2]

End point description

The numbers of subjects who experienced Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, and Infusion Associated Reactions (IARs). Summary is based on treatment-emergent AEs (TEAEs), defined as AEs that occurred following the initiation of study treatment with alglucosidase alfa. Subjects with long-term exposure to alglucosidase alfa (those from the Alglucosidase Alfa/Alglucosidase Alfa treatment group) are included. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). The safety population includes all subjects randomized to alglucosidase alfa treatment in AGLU02704 (NCT00158600) who received at least one infusion of alglucosidase alfa.

End point type

Primary

End point timeframe

Week 0 to 2.5 years

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: Only descriptive data were planned to be reported for efficacy analysis.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The outcome focus only those subjects who received Alglucosidase Alfa during study AGLU02704.

End point values	Alglucosidase Alfa/Alglucosidase Alfa
Number of subjects analysed	60
Units: subjects
Subjects with any AEs	60
Subjects with Treatment-Related AEs	37
Subjects with Infusion-Associated Reactions	21
Subjects with Serious AEs	15
Subjects with Severe AEs	16
Subjects- Discontinued Due to AEs (incl death)	3
Subjects Who Died	1

No statistical analyses for this end point

Primary: Baseline Values (Week 0) of Functional Endurance as Measured by Six-Minute Walk Test (6MWT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

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End point title

Baseline Values (Week 0) of Functional Endurance as Measured by Six-Minute Walk Test (6MWT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) ^[3] ^[4]

End point description

End point type

Primary

End point timeframe

Week 0

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: Only descriptive data were planned to be reported for efficacy analysis.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The outcome focus only those subjects who received Alglucosidase Alfa during study AGLU02704.

End point values	Alglucosidase Alfa/Alglucosidase Alfa
Number of subjects analysed	60
Units: meters
arithmetic mean (standard deviation)	332.2 ± 126.69

No statistical analyses for this end point

Primary: Change From Baseline (Week 0) in the Six-Minute Walk Test (6MWT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

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End point title

Change From Baseline (Week 0) in the Six-Minute Walk Test (6MWT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) ^[5] ^[6]

End point description

Six-Minute Walk Test (6MWT) measures the distance walked (in meters) in 6 minutes. A longer distance indicates greater endurance. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). Change is calculated as the value minus the baseline value. Intent-to-treat population of subjects who had both baseline (Week 0) and Week 104 data.

End point type

Primary

End point timeframe

Week 0, Week 104

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: Analysis was descriptive, hence no statistical analysis is reported.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The outcome focus only those subjects who received Alglucosidase Alfa during study AGLU02704.

End point values	Alglucosidase Alfa/Alglucosidase Alfa
Number of subjects analysed	53
Units: meters
arithmetic mean (standard deviation)	21.3 ± 78.02

No statistical analyses for this end point

Primary: Baseline Values (Week 0) for Percent Predicted Forced Vital Capacity (FVC) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

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End point title

Baseline Values (Week 0) for Percent Predicted Forced Vital Capacity (FVC) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) ^[7] ^[8]

End point description

Forced vital capacity (FVC) is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC is the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted forced vital capacity is based on a formula using sex, age and height of a person, and is an estimate of healthy lung capacity. Percent of predicted FVC = (observed value)/(predicted value) * 100%. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). Intent-to-treat population.

End point type

Primary

End point timeframe

Week 0

Notes
[7] - 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: Only descriptive data were planned to be reported for efficacy analysis.
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The outcome focus only those subjects who received Alglucosidase Alfa during study AGLU02704.

End point values	Alglucosidase Alfa/Alglucosidase Alfa
Number of subjects analysed	60
Units: percent of predicted FVC
arithmetic mean (standard deviation)	55.4 ± 14.44

No statistical analyses for this end point

Primary: Change From Baseline (Week 0) in the Percent Predicted Forced Vital Capacity (FVC) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

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End point title

Change From Baseline (Week 0) in the Percent Predicted Forced Vital Capacity (FVC) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) ^[9] ^[10]

End point description

End point type

Primary

End point timeframe

Week 0, Week 104

Notes
[9] - 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: Analysis was descriptive, hence no statistical analysis is reported.
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The outcome focus only those subjects who received Alglucosidase Alfa during study AGLU02704.

End point values	Alglucosidase Alfa/Alglucosidase Alfa
Number of subjects analysed	53
Units: percent of predicted FVC
arithmetic mean (standard deviation)	0.8 ± 6.68

No statistical analyses for this end point

Secondary: Baseline Values (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

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End point title

Baseline Values (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) ^[11]

End point description

Quantitative muscle testing (QMT) is a standardized system to measure muscle force production during maximal voluntary isometric contraction. QMT data were collected directly from sensors into laptop computers. Predicted normal values for QMT are based on a formula using sex, age and body mass index of a person, and are an estimate of healthy muscle force. Percent of predicted QMT = (observed value)/(predicted value) * 100%. The QMT Leg Score is the average of the bilateral means for percent predicted knee flexors and extensors. A value of 100% indicates 'normal' muscle strength. Intent-to-treat population.

End point type

Secondary

End point timeframe

Week 0

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The outcome focus only those subjects who received Alglucosidase Alfa during study AGLU02704.

End point values	Alglucosidase Alfa/Alglucosidase Alfa
Number of subjects analysed	60
Units: percent of predicted QMT
arithmetic mean (standard deviation)	37.7 ± 18.88

No statistical analyses for this end point

Secondary: Change From Baseline (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

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End point title

Change From Baseline (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) ^[12]

End point description

End point type

Secondary

End point timeframe

Week 0, Week 104

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The outcome focus only those subjects who received Alglucosidase Alfa during study AGLU02704.

End point values	Alglucosidase Alfa/Alglucosidase Alfa
Number of subjects analysed	53
Units: percent of predicted QMT
arithmetic mean (standard deviation)	2.1 ± 11.06

No statistical analyses for this end point

Secondary: Baseline Values (Week 0) for Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

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End point title

Baseline Values (Week 0) for Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) ^[13]

End point description

The Medical Outcomes Study Short Form (MOS SF)-36 questionnaire consists of 36 items grouped into 8 domains designed to assess generic health-related quality of life in healthy and ill adult populations. Physical Component Score reports the four domains of physical functioning, role-physical, bodily pain, and general health and are standardized as Z-scores (scale of 0-100). Higher scores are associated with better quality of life. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). Intent-to-treat population of subjects with valid baseline (Week 0) PCS surveys.

End point type

Secondary

End point timeframe

Week 0

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only descriptive data were planned to be reported for efficacy analysis.

End point values	Alglucosidase Alfa/Alglucosidase Alfa
Number of subjects analysed	58
Units: units on a scale
arithmetic mean (standard deviation)	34.33 ± 8.934

No statistical analyses for this end point

Secondary: Change From Baseline in Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

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End point title

Change From Baseline in Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600) ^[14]

End point description

The Medical Outcomes Study Short Form (MOS SF)-36 questionnaire consists of 36 items grouped into 8 domains designed to assess generic health-related quality of life in healthy and ill adult populations. Physical Component Score reports the four domains of physical functioning, role-physical, bodily pain, and general health and is standardized as Z-scores (scale of 0-100). Higher scores are associated with better quality of life. Change is calculated as the value minus the baseline value. Time frames are stated from the start of the double-blind study AGLU02704 (NCT00158600). Intent-to-treat population of subjects who had valid baseline (Week 0) and Week 104 data.

End point type

Secondary

End point timeframe

Week 0 , Week 104

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The outcome focus only those subjects who received Alglucosidase Alfa during study AGLU02704.

End point values	Alglucosidase Alfa/Alglucosidase Alfa
Number of subjects analysed	49
Units: units on a scale
arithmetic mean (standard deviation)	0.64 ± 7.618

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events for the Alglucosidase Alfa/Alglucosidase Alfa group cover up to 2.5 years (Week 0 to 2.5 years), and for Placebo/Alglucosidase Alfa group cover up to 1.0 year (Week 78 to 2.5 years) regardless of seriousness or relationship to study drug.

Adverse event reporting additional description

Reported AEs and deaths are treatment-emergent that is AEs and deaths that occurred following the initiation of study treatment i.e. alglucosidase alfa or placebo.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

9.1

Reporting group title

Alglucosidase Alfa/Alglucosidase Alfa

Reporting group description

Reporting group title

Placebo/Alglucosidase Alfa

Reporting group description

Serious adverse events	Alglucosidase Alfa/Alglucosidase Alfa	Placebo/Alglucosidase Alfa
Total subjects affected by serious adverse events
subjects affected / exposed	15 / 60 (25.00%)	2 / 26 (7.69%)
number of deaths (all causes)	1	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix Carcinoma Stage Ii
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Aneurysm
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Chest Discomfort
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Non-Cardiac Chest Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Hypersensitivity
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Lung Disorder
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Throat Tightness
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal Compression Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Coronary Artery Disease
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Supraventricular Tachycardia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Brain Stem Ischaemia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastric Ulcer
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioneurotic Oedema
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Hydronephrosis
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal Cyst
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Intervertebral Disc Protrusion
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Gastroenteritis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Alglucosidase Alfa/Alglucosidase Alfa	Placebo/Alglucosidase Alfa
Total subjects affected by non serious adverse events
subjects affected / exposed	60 / 60 (100.00%)	25 / 26 (96.15%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Skin Papilloma
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Vascular disorders
Aneurysm
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Cardiovascular Insufficiency
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Diastolic Hypotension
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Flushing
subjects affected / exposed	3 / 60 (5.00%)	1 / 26 (3.85%)
occurrences all number	5	1
Haematoma
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Hot Flush
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	5	0
Hypertension
subjects affected / exposed	5 / 60 (8.33%)	0 / 26 (0.00%)
occurrences all number	5	0
Hypotension
subjects affected / exposed	2 / 60 (3.33%)	1 / 26 (3.85%)
occurrences all number	3	1
Raynaud's Phenomenon
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Vasoconstriction
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
General disorders and administration site conditions
Adverse Drug Reaction
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Application Site Vesicles
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Asthenia
subjects affected / exposed	4 / 60 (6.67%)	0 / 26 (0.00%)
occurrences all number	5	0
Axillary Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Catheter Related Complication
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Catheter Site Pain
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	8	0
Chest Discomfort
subjects affected / exposed	7 / 60 (11.67%)	0 / 26 (0.00%)
occurrences all number	17	0
Chest Pain
subjects affected / exposed	6 / 60 (10.00%)	2 / 26 (7.69%)
occurrences all number	7	2
Chills
subjects affected / exposed	4 / 60 (6.67%)	1 / 26 (3.85%)
occurrences all number	5	3
Disease Progression
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Fatigue
subjects affected / exposed	13 / 60 (21.67%)	4 / 26 (15.38%)
occurrences all number	19	5
Feeling Abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Feeling Cold
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Feeling Hot
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	4	0
Gait Disturbance
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Influenza Like Illness
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Infusion Site Bruising
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Infusion Site Pain
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Infusion Site Paraesthesia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Infusion Site Reaction
subjects affected / exposed	7 / 60 (11.67%)	0 / 26 (0.00%)
occurrences all number	10	0
Injection Site Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Injection Site Phlebitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Local Swelling
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	14	0
Malaise
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	3	0
Nodule
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Oedema Peripheral
subjects affected / exposed	13 / 60 (21.67%)	1 / 26 (3.85%)
occurrences all number	19	1
Pain
subjects affected / exposed	6 / 60 (10.00%)	0 / 26 (0.00%)
occurrences all number	9	0
Pitting Oedema
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Puncture Site Haemorrhage
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Pyrexia
subjects affected / exposed	12 / 60 (20.00%)	2 / 26 (7.69%)
occurrences all number	13	2
Thirst
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	2 / 60 (3.33%)	1 / 26 (3.85%)
occurrences all number	24	2
Seasonal Allergy
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Reproductive system and breast disorders
Breast Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Breast Swelling
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Breast Tenderness
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Dysmenorrhoea
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Fibrocystic Breast Disease
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Menorrhagia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Menstrual Discomfort
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Menstruation Irregular
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Pelvic Pain
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	4	0
Vaginal Haemorrhage
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Respiratory, thoracic and mediastinal disorders
Bronchospasm
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Choking
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Cough
subjects affected / exposed	8 / 60 (13.33%)	5 / 26 (19.23%)
occurrences all number	9	5
Dyspnoea
subjects affected / exposed	9 / 60 (15.00%)	1 / 26 (3.85%)
occurrences all number	13	1
Dyspnoea Exertional
subjects affected / exposed	5 / 60 (8.33%)	0 / 26 (0.00%)
occurrences all number	9	0
Epistaxis
subjects affected / exposed	4 / 60 (6.67%)	0 / 26 (0.00%)
occurrences all number	9	0
Increased Bronchial Secretion
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Lung Disorder
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Lung Infiltration
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Nasal Congestion
subjects affected / exposed	8 / 60 (13.33%)	0 / 26 (0.00%)
occurrences all number	9	0
Pharyngolaryngeal Pain
subjects affected / exposed	14 / 60 (23.33%)	3 / 26 (11.54%)
occurrences all number	24	3
Postnasal Drip
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Respiratory Distress
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Respiratory Failure
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Respiratory Tract Congestion
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	3	0
Rhinorrhoea
subjects affected / exposed	3 / 60 (5.00%)	1 / 26 (3.85%)
occurrences all number	3	1
Sinus Congestion
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	4	0
Sleep Apnoea Syndrome
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Throat Irritation
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Sneezing
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Throat Tightness
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Upper Respiratory Tract Congestion
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Wheezing
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	1	1
Psychiatric disorders
Anger
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Anxiety
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	5	0
Depression
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	4	0
Insomnia
subjects affected / exposed	9 / 60 (15.00%)	0 / 26 (0.00%)
occurrences all number	14	0
Post-Traumatic Stress Disorder
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Stress
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	9	0
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Aspartate Aminotransferase Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Blood Creatine Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Blood Folate Decreased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Blood Glucose Increased
subjects affected / exposed	1 / 60 (1.67%)	2 / 26 (7.69%)
occurrences all number	1	2
Blood Pressure Increased
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	3	0
Blood Urine Present
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Blood Uric Acid Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Body Temperature Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Carbon Dioxide Increased
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	1	1
Crystal Urine Present
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Electrocardiogram Qt Corrected Interval Prolonged
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Electrocardiogram St Segment Depression
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Electrocardiogram T Wave Amplitude Decreased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Electrocardiogram Abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Fungus Urine Test Positive
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Glucose Urine Present
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Haematocrit Decreased
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Neutrophil Count Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Oxygen Saturation Decreased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Protein Urine Present
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	3	0
Specific Gravity Urine Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Tandem Gait Test Abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Urine Analysis Abnormal
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Urine Ketone Body Present
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Weight Decreased
subjects affected / exposed	2 / 60 (3.33%)	1 / 26 (3.85%)
occurrences all number	2	1
White Blood Cell Count Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
White Blood Cells Urine Positive
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Injury, poisoning and procedural complications
Animal Bite
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Animal Scratch
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Arthropod Sting
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Arthropod Bite
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Concussion
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Back Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Contusion
subjects affected / exposed	9 / 60 (15.00%)	1 / 26 (3.85%)
occurrences all number	12	2
Excoriation
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Fall
subjects affected / exposed	39 / 60 (65.00%)	13 / 26 (50.00%)
occurrences all number	281	52
Femur Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Foot Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Humerus Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Head Injury
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Injury Corneal
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Injury
subjects affected / exposed	4 / 60 (6.67%)	0 / 26 (0.00%)
occurrences all number	4	0
Joint Sprain
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Ligament Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Limb Crushing Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Limb Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Mouth Injury
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Muscle Strain
subjects affected / exposed	6 / 60 (10.00%)	2 / 26 (7.69%)
occurrences all number	10	2
Neck Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Pelvic Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Post-Traumatic Pain
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Procedural Pain
subjects affected / exposed	9 / 60 (15.00%)	1 / 26 (3.85%)
occurrences all number	11	1
Radial Nerve Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Rib Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Road Traffic Accident
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Scratch
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Skin Laceration
subjects affected / exposed	5 / 60 (8.33%)	0 / 26 (0.00%)
occurrences all number	7	0
Soft Tissue Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Tendon Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Tendon Rupture
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Thermal Burn
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Tooth Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Tooth Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Traumatic Ulcer
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Vaccination Complication
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Wound
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	3	0
Cardiac disorders
Angina Pectoris
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Atrial Hypertrophy
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Bundle Branch Block Left
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Bundle Branch Block Right
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Coronary Artery Disease
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	3	0
Palpitations
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	9	0
Tachycardia
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Sinus Tachycardia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Tricuspid Valve Incompetence
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Ventricular Dysfunction
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Ventricular Hypertrophy
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Nervous system disorders
Areflexia
subjects affected / exposed	5 / 60 (8.33%)	2 / 26 (7.69%)
occurrences all number	8	2
Balance Disorder
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	3	0
Burning Sensation
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	3	0
Carpal Tunnel Syndrome
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Dizziness
subjects affected / exposed	16 / 60 (26.67%)	3 / 26 (11.54%)
occurrences all number	38	4
Dizziness Postural
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Facial Palsy
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Headache
subjects affected / exposed	31 / 60 (51.67%)	6 / 26 (23.08%)
occurrences all number	113	21
Hyperreflexia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Hypoaesthesia
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	3	0
Hyporeflexia
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	3	0
Intercostal Neuralgia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Lethargy
subjects affected / exposed	2 / 60 (3.33%)	1 / 26 (3.85%)
occurrences all number	4	1
Loss Of Consciousness
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	3	0
Migraine
subjects affected / exposed	4 / 60 (6.67%)	0 / 26 (0.00%)
occurrences all number	7	0
Nerve Compression
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Neuralgia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Paraesthesia
subjects affected / exposed	7 / 60 (11.67%)	0 / 26 (0.00%)
occurrences all number	17	0
Sciatica
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Sensory Disturbance
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	1	1
Sinus Headache
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	1	1
Somnolence
subjects affected / exposed	4 / 60 (6.67%)	0 / 26 (0.00%)
occurrences all number	6	0
Syncope Vasovagal
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Tremor
subjects affected / exposed	4 / 60 (6.67%)	1 / 26 (3.85%)
occurrences all number	4	2
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	4 / 60 (6.67%)	0 / 26 (0.00%)
occurrences all number	4	0
Lymphadenopathy
subjects affected / exposed	5 / 60 (8.33%)	0 / 26 (0.00%)
occurrences all number	6	0
Macrocytosis
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Normochromic Normocytic Anaemia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Spontaneous Haematoma
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Ear and labyrinth disorders
Cerumen Impaction
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Auricular Swelling
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Ear Congestion
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Ear Discomfort
subjects affected / exposed	5 / 60 (8.33%)	0 / 26 (0.00%)
occurrences all number	33	0
Ear Pain
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	4	0
Hypoacusis
subjects affected / exposed	23 / 60 (38.33%)	3 / 26 (11.54%)
occurrences all number	39	3
Presbyacusis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Tinnitus
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	3	0
Vertigo
subjects affected / exposed	5 / 60 (8.33%)	0 / 26 (0.00%)
occurrences all number	8	0
Vertigo Positional
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Eye disorders
Altered Visual Depth Perception
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Asthenopia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Cataract
subjects affected / exposed	4 / 60 (6.67%)	1 / 26 (3.85%)
occurrences all number	4	1
Conjunctivitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Diplopia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Dry Eye
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Eye Irritation
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Eye Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Eye Pruritus
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Eyelid Ptosis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Keratoconjunctivitis Sicca
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Photophobia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Pinguecula
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Retinal Detachment
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Vision Blurred
subjects affected / exposed	4 / 60 (6.67%)	0 / 26 (0.00%)
occurrences all number	4	0
Visual Acuity Reduced
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Visual Disturbance
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Vitreous Floaters
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Abdominal Distension
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Abdominal Mass
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Abdominal Pain
subjects affected / exposed	5 / 60 (8.33%)	0 / 26 (0.00%)
occurrences all number	6	0
Abdominal Pain Lower
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Abdominal Pain Upper
subjects affected / exposed	6 / 60 (10.00%)	1 / 26 (3.85%)
occurrences all number	23	1
Abdominal Tenderness
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Anal Fissure
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Anorectal Disorder
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Aphthous Stomatitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Bowel Sounds Abnormal
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Chapped Lips
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Constipation
subjects affected / exposed	7 / 60 (11.67%)	0 / 26 (0.00%)
occurrences all number	9	0
Crohn's Disease
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Diarrhoea
subjects affected / exposed	20 / 60 (33.33%)	2 / 26 (7.69%)
occurrences all number	49	2
Diverticulum Intestinal
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Dry Mouth
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Dyspepsia
subjects affected / exposed	7 / 60 (11.67%)	0 / 26 (0.00%)
occurrences all number	11	0
Epigastric Discomfort
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Flatulence
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Food Poisoning
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Gastrooesophageal Reflux Disease
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	4	0
Gingivitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Haematochezia
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	1	1
Haemorrhoids
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Inguinal Hernia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Lip Swelling
subjects affected / exposed	2 / 60 (3.33%)	1 / 26 (3.85%)
occurrences all number	7	1
Mouth Ulceration
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Nausea
subjects affected / exposed	15 / 60 (25.00%)	2 / 26 (7.69%)
occurrences all number	46	26
Oesophageal Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Oral Pruritus
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Paraesthesia Oral
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Rectal Haemorrhage
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Retching
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Stomach Discomfort
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	4	0
Swollen Tongue
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Toothache
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Vomiting
subjects affected / exposed	14 / 60 (23.33%)	2 / 26 (7.69%)
occurrences all number	17	2
Skin and subcutaneous tissue disorders
Cold Sweat
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	4	0
Actinic Keratosis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Decubitus Ulcer
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Dermatitis Contact
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Dry Skin
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Ecchymosis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Erythema
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	5	0
Heat Rash
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Hyperhidrosis
subjects affected / exposed	6 / 60 (10.00%)	1 / 26 (3.85%)
occurrences all number	14	1
Ingrowing Nail
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Photosensitivity Reaction
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Night Sweats
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Pruritus
subjects affected / exposed	8 / 60 (13.33%)	3 / 26 (11.54%)
occurrences all number	23	4
Psoriasis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Rash
subjects affected / exposed	9 / 60 (15.00%)	1 / 26 (3.85%)
occurrences all number	18	1
Rash Macular
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	5	0
Rash Maculo-Papular
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	4	0
Rash Pruritic
subjects affected / exposed	4 / 60 (6.67%)	0 / 26 (0.00%)
occurrences all number	8	0
Rash Papular
subjects affected / exposed	5 / 60 (8.33%)	0 / 26 (0.00%)
occurrences all number	6	0
Rosacea
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Skin Hyperpigmentation
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Skin Inflammation
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Skin Lesion
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Skin Nodule
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	21	0
Skin Odour Abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Subcutaneous Nodule
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Urticaria
subjects affected / exposed	7 / 60 (11.67%)	1 / 26 (3.85%)
occurrences all number	25	1
Urticaria Contact
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	1	1
Haematuria
subjects affected / exposed	3 / 60 (5.00%)	1 / 26 (3.85%)
occurrences all number	6	2
Leukocyturia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Nephrolithiasis
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	4	0
Pollakiuria
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Proteinuria
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	8	0
Pyuria
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Renal Cyst
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Urge Incontinence
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Urinary Incontinence
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Urine Flow Decreased
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Urine Odour Abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	25 / 60 (41.67%)	4 / 26 (15.38%)
occurrences all number	49	6
Arthritis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Back Pain
subjects affected / exposed	19 / 60 (31.67%)	6 / 26 (23.08%)
occurrences all number	38	6
Bone Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Bursitis
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	1	1
Buttock Pain
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	4	0
Costochondritis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Groin Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Flank Pain
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	1	1
Joint Contracture
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	2
Joint Crepitation
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Muscle Atrophy
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Muscle Spasms
subjects affected / exposed	17 / 60 (28.33%)	5 / 26 (19.23%)
occurrences all number	30	6
Muscle Contracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Muscle Twitching
subjects affected / exposed	6 / 60 (10.00%)	0 / 26 (0.00%)
occurrences all number	8	0
Muscle Tightness
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	1	2
Musculoskeletal Chest Pain
subjects affected / exposed	6 / 60 (10.00%)	1 / 26 (3.85%)
occurrences all number	10	1
Muscular Weakness
subjects affected / exposed	11 / 60 (18.33%)	2 / 26 (7.69%)
occurrences all number	19	3
Musculoskeletal Discomfort
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Musculoskeletal Disorder
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Musculoskeletal Pain
subjects affected / exposed	10 / 60 (16.67%)	4 / 26 (15.38%)
occurrences all number	21	6
Myalgia
subjects affected / exposed	16 / 60 (26.67%)	3 / 26 (11.54%)
occurrences all number	53	5
Musculoskeletal Stiffness
subjects affected / exposed	8 / 60 (13.33%)	0 / 26 (0.00%)
occurrences all number	13	0
Nose Deformity
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Neck Pain
subjects affected / exposed	9 / 60 (15.00%)	1 / 26 (3.85%)
occurrences all number	11	1
Osteoarthritis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Osteopenia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Osteoporosis
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	3	0
Senile Ankylosing Vertebral Hyperostosis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Pain In Extremity
subjects affected / exposed	23 / 60 (38.33%)	2 / 26 (7.69%)
occurrences all number	44	2
Temporomandibular Joint Syndrome
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Sensation Of Heaviness
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	6	0
Tendonitis
subjects affected / exposed	2 / 60 (3.33%)	1 / 26 (3.85%)
occurrences all number	4	1
Tenosynovitis Stenosans
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Infections and infestations
Acute Tonsillitis
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Bronchiolitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Bronchitis
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	3	0
Bronchitis Acute
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Cellulitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Cystitis
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	3	0
Dermatophytosis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Ear Infection
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Eye Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	2	0
Folliculitis
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Fungal Infection
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Fungal Skin Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Gastroenteritis
subjects affected / exposed	8 / 60 (13.33%)	0 / 26 (0.00%)
occurrences all number	8	0
Gastroenteritis Viral
subjects affected / exposed	4 / 60 (6.67%)	0 / 26 (0.00%)
occurrences all number	7	0
Gingival Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Herpes Simplex
subjects affected / exposed	4 / 60 (6.67%)	1 / 26 (3.85%)
occurrences all number	8	1
Herpes Virus Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Herpes Zoster
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Influenza
subjects affected / exposed	8 / 60 (13.33%)	3 / 26 (11.54%)
occurrences all number	13	3
Kidney Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Laryngitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Localised Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Lower Respiratory Tract Infection
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Mucosal Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Nasopharyngitis
subjects affected / exposed	29 / 60 (48.33%)	8 / 26 (30.77%)
occurrences all number	68	10
Otitis Media
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Pharyngitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Pharyngitis Streptococcal
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	1	1
Pneumonia
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Postoperative Wound Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Rash Pustular
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	2
Respiratory Tract Infection
subjects affected / exposed	3 / 60 (5.00%)	1 / 26 (3.85%)
occurrences all number	3	1
Rhinitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Sinusitis
subjects affected / exposed	9 / 60 (15.00%)	3 / 26 (11.54%)
occurrences all number	17	3
Tinea Pedis
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	4	0
Tonsillitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Tooth Abscess
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Tooth Infection
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	2	0
Upper Respiratory Tract Infection
subjects affected / exposed	20 / 60 (33.33%)	6 / 26 (23.08%)
occurrences all number	29	6
Urinary Tract Infection Bacterial
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	2
Urinary Tract Infection
subjects affected / exposed	5 / 60 (8.33%)	2 / 26 (7.69%)
occurrences all number	7	3
Vaginal Infection
subjects affected / exposed	1 / 60 (1.67%)	1 / 26 (3.85%)
occurrences all number	5	1
Viral Infection
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	3	0
Wound Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Metabolism and nutrition disorders
Anorexia
subjects affected / exposed	0 / 60 (0.00%)	1 / 26 (3.85%)
occurrences all number	0	1
Decreased Appetite
subjects affected / exposed	2 / 60 (3.33%)	0 / 26 (0.00%)
occurrences all number	3	0
Gout
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Hyperglycaemia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Hypernatraemia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Hypertriglyceridaemia
subjects affected / exposed	1 / 60 (1.67%)	0 / 26 (0.00%)
occurrences all number	1	0
Hypokalaemia
subjects affected / exposed	3 / 60 (5.00%)	0 / 26 (0.00%)
occurrences all number	5	0

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Were there any global substantial amendments to the protocol? Yes

27 Oct 2006

It included following statements: 1. Oligosaccharide testing in plasma was removed because testing in urine was deemed to be better suited for use in clinical practice as urine samples were collected non-invasively, analysis was rapid, and the concentrations were several orders of magnitude higher than in plasma. 2. Inclusion criterion was amended due to ethical concerns for requiring subjects to be treated in the placebo-controlled trial beyond the originally planned 52 weeks to be eligible to participate in the open-label trial in regions where alglucosidase alfa was not provided to subjects with late-onset Pompe disease through government reimbursement or charitable access mechanisms, as subjects in these regions may have felt that their options differ from those in regions where alglucosidase alfa was available via the mechanisms outlined. In actuality, all 81 subjects who enrolled in the Late-Onset Treatment Study (LOTS) extension completed the full 78 weeks in LOTS. 3. Guidance on the infusion rates was added to the treatments administered section, primarily that Infusion-Associated Reactions (IARs) were more likely to occur at higher infusion rates and that the infusion rate might be slowed and/or temporarily stopped in the event of an IAR. 4. Assessment of vital signs during infusion was changed to immediately prior to any infusion rate change rather than every 30 minutes and immediately prior to any infusion rate change if the time point was different. Additionally, the windows for assessment of vital signs were clarified to assure that vital signs assessments before and during infusion were to within 15 minutes before the infusion or an infusion rate change, while the window for assessment of vital signs at the completion of the post-infusion observation period remained 15 minutes before or after the set time.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
An Open-Label Extension Study of Patients with Late-Onset Pompe Disease Who Were Previously Enrolled in Protocol AGLU02704

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Summary of Subjects Reporting Treatment-Emergent Adverse Events For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Summary of Subjects Reporting Treatment-Emergent Adverse Events For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Baseline Values (Week 0) of Functional Endurance as Measured by Six-Minute Walk Test (6MWT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Baseline Values (Week 0) of Functional Endurance as Measured by Six-Minute Walk Test (6MWT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Change From Baseline (Week 0) in the Six-Minute Walk Test (6MWT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Change From Baseline (Week 0) in the Six-Minute Walk Test (6MWT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Baseline Values (Week 0) for Percent Predicted Forced Vital Capacity (FVC) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Baseline Values (Week 0) for Percent Predicted Forced Vital Capacity (FVC) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Change From Baseline (Week 0) in the Percent Predicted Forced Vital Capacity (FVC) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Change From Baseline (Week 0) in the Percent Predicted Forced Vital Capacity (FVC) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Baseline Values (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Baseline Values (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Change From Baseline (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Change From Baseline (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Baseline Values (Week 0) for Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Baseline Values (Week 0) for Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Change From Baseline in Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Change From Baseline in Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Austria
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Outside EU/EEA

Clinical trials

Clinical Trial Results: An Open-Label Extension Study of Patients with Late-Onset Pompe Disease Who Were Previously Enrolled in Protocol AGLU02704

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Summary of Subjects Reporting Treatment-Emergent Adverse Events For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Summary of Subjects Reporting Treatment-Emergent Adverse Events For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Baseline Values (Week 0) of Functional Endurance as Measured by Six-Minute Walk Test (6MWT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Baseline Values (Week 0) of Functional Endurance as Measured by Six-Minute Walk Test (6MWT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Change From Baseline (Week 0) in the Six-Minute Walk Test (6MWT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Change From Baseline (Week 0) in the Six-Minute Walk Test (6MWT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Baseline Values (Week 0) for Percent Predicted Forced Vital Capacity (FVC) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Baseline Values (Week 0) for Percent Predicted Forced Vital Capacity (FVC) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Change From Baseline (Week 0) in the Percent Predicted Forced Vital Capacity (FVC) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Primary: Change From Baseline (Week 0) in the Percent Predicted Forced Vital Capacity (FVC) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Baseline Values (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Baseline Values (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Change From Baseline (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Change From Baseline (Week 0) for Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT) at Week 104 For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Baseline Values (Week 0) for Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Baseline Values (Week 0) for Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Change From Baseline in Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Secondary: Change From Baseline in Quality of Life Related to Physical Component Score (PCS) as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey For Subjects Treated With Alglucosidase Alfa During Study AGLU02704 (NCT00158600)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
An Open-Label Extension Study of Patients with Late-Onset Pompe Disease Who Were Previously Enrolled in Protocol AGLU02704