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Clinical Trial Results:
Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy and Pharmacokinetics of Myozyme in Patients With Late-Onset Pompe Disease.

Summary
EudraCT number	2005-002759-42
Trial protocol	DE
Global end of trial date	28 Sep 2007

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

AGLU02704

ISRCTN number

US NCT number

NCT00158600

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

21 Nov 2007

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

28 Sep 2007

Was the trial ended prematurely?

Main objective of the trial

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) 3) to determine the effect of Myozyme treatment on respiratory muscle weakness as measured by Forced Vital Capacity (FVC) in the upright position ; and 4) to determine in a subset of subjects the PK profile of Myozyme in subjects with late-onset Pompe disease. The study wil be considered to have met its primary efficacy objective if a statistically significant treatment effect of Myozyme over placebo is demonstrated in the 6 MWT distance walked.

Protection of trial subjects

Pediatric subjects: The study was conducted by investigators experienced in the treatment of pediatric subjects. The parent(s) or guardian(s) as well as the children were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time. In addition to the consent form for the parent(s)/guardian(s), an assent form in child-appropriate language was provided and explained to the child. Repeated invasive procedures were minimized. The number of blood samples as well as the amount of blood drawn were adjusted according to age and weight. A topical anesthesia may have been used to minimize distress and discomfort. Adult 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

06 Sep 2005

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 10

Country: Number of subjects enrolled

United States: 58

Country: Number of subjects enrolled

Netherlands: 22

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

One hundred subjects screened and 90 enrolled.

Period 1 title

Overall Study (overall period)

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

Arm description

Alglucosidase alfa for 78 weeks.

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

Alglucosidase alfa at 20 milligrams (mg)/kilogram (kg) of body weight every other week (qow).

Placebo

Arm description

Placebo for 78 weeks.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for infusion

Routes of administration

Intravenous use

Dosage and administration details

Placebo matched to alglucosidase alfa every other week (qow).

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

Baseline characteristics

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Reporting group title

Alglucosidase Alfa

Reporting group description

Alglucosidase alfa for 78 weeks.

Reporting group title

Placebo

Reporting group description

Placebo for 78 weeks.

Reporting group values	Alglucosidase Alfa	Placebo	Total
Number of subjects	60	30	90
Age categorical
Units: Subjects
Age continuous
Age at First Infusion
Units: years
arithmetic mean (standard deviation)	45.3 ( 12.37 )	42.6 ( 11.63 )	-
Gender categorical
Units: Subjects
Female	26	19	45
Male	34	11	45
Race/Ethnicity
Units: Subjects
Hispanic	1	1	2
Asian	1	1	2
Black or African American	0	0	0
White	57	27	84
Unknown or not reported	1	1	2

End points

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Reporting group title

Alglucosidase Alfa

Reporting group description

Alglucosidase alfa for 78 weeks.

Reporting group title

Placebo

Reporting group description

Placebo for 78 weeks.

Primary: Summary of Subjects Reporting Treatment-Emergent Adverse Events

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End point title

Summary of Subjects Reporting Treatment-Emergent Adverse Events ^[1]

End point description

Overall safety summary of subjects experiencing 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, i.e., alglucosidase alfa or placebo. All subjects who received any amount of study treatment comprise the safety population. Subjects were considered, for safety analysis, to be in the treatment group of the treatment they actually received. Missing or invalid safety or resource utilization data were not replaced.

End point type

Primary

End point timeframe

weeks 0-78

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: Since analysis is descriptive in nature, statistical data could not be provided.

End point values	Alglucosidase Alfa	Placebo
Number of subjects analysed	60	30
Units: subjects
Subjects with Any AEs	60	30
Subjects with Treatment-Related AEs	32	17
Subjects with Infusion-Associated Reactions	17	7
Subjects with SAEs	13	6
Subjects with Severe AEs	14	10
Subjects who Discontinued Due to AEs (incl death)	3	1
Subjects who Died	1	0

No statistical analyses for this end point

Primary: Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline

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End point title

Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline

End point description

Mean distance walked gives an indication of functional endurance. The greater the distance, the greater the endurance. Mean values of distance walked in a six-minute walk test are offered for baseline, week 78 (or last available observation), and the mean change from baseline (at week 78 or last available post-baseline observation). Intent-to-Treat (ITT) population. Last observation carried forward. The last available distance walked for one subject was the Baseline visit; therefore, this subject was excluded from the change from baseline calculation.

End point type

Primary

End point timeframe

weeks 0, 78

End point values	Alglucosidase Alfa	Placebo
Number of subjects analysed	60	30
Units: meters
arithmetic mean (standard deviation)
Distance Walked at Baseline	332.2 ( 126.69 )	317.93 ( 132.29 )
Distance Walked at Last Available Observation	357.85 ( 141.32 )	313.07 ( 144.69 )
Change at Last Available Observation from Baseline	26.08 ( 64.41 )	-4.87 ( 45.24 )

Alglucosidase Alfa vs Placebo

Statistical analysis description

The difference between alglucosidase alfa and placebo treatment groups in change in distance walked from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.

Comparison groups

Alglucosidase Alfa v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0347 ^[2]

Method

ANCOVA

Parameter type

Difference

Point estimate

28.12

Confidence interval

level

95%

sides

2-sided

lower limit

2.07

upper limit

54.17

Notes
[2] - The threshold for determining statistical significance was 0.05. A fixed testing sequence procedure was used to preserve an overall error rate of 5% for the co-primary efficacy endpoints by linking the test of FVC to the result of 6MWT.

Primary: Percent of Predicted Forced Vital Capacity (FVC)

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End point title

Percent of Predicted Forced Vital Capacity (FVC)

End point description

Forced vital capacity is a standard pulmonary function test used to quantify respiratory muscle weakness. Forced vital capacity (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%. ITT population. Last observation carried forward.

End point type

Primary

End point timeframe

weeks 0, 78

End point values	Alglucosidase Alfa	Placebo
Number of subjects analysed	60	30
Units: percent predicted FVC
arithmetic mean (standard deviation)
Baseline (week 0)	55.43 ( 14.44 )	53 ( 15.66 )
Week 78 (or last observation)	56.71 ( 16.3 )	50.7 ( 14.88 )
Change at Week 78 from Baseline	1.25 ( 5.55 )	-2.3 ( 4.33 )

Alglucosidase Alfa vs Placebo

Statistical analysis description

The difference between alglucosidase alfa and placebo treatment groups in change in % predicted FVC from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.

Comparison groups

Alglucosidase Alfa v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0055 ^[3]

Method

ANCOVA

Parameter type

Difference

Point estimate

3.4

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

5.77

Notes
[3] - The threshold for determining statistical significance is 0.05. A fixed testing sequence procedure was used to preserve an overall error rate of 5% for the co-primary efficacy endpoints by linking the test of FVC to the result of 6MWT.

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)

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End point title

Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC) ^[4] ^[5]

End point description

Area under the plasma concentration versus time curve from time zero (pre-dose) to 16 hours after the end of infusion. Blood sample time points were 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes. The subgroup of subjects for whom pharmacokinetic samples were obtained was based on those study sites that could accommodate pharmacokinetic sampling needs.

End point type

Primary

End point timeframe

weeks 0, 12 and 52

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: Only descriptive data are reported for pharmacokinetic analysis.
[5] - 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: Pharmacokinetic data were measured only for alglucosidase alfa, hence data were provided for this arm only.

End point values	Alglucosidase Alfa
Number of subjects analysed	32
Units: ug*h/mL
arithmetic mean (standard deviation)
Week 0	2672.47 ( 1139.85 )
Week 12	2386.76 ( 555.09 )
Week 52	2699.28 ( 999.97 )
Pooled	2586.17 ( 933.28 )

No statistical analyses for this end point

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)

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End point title

Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax) ^[6] ^[7]

End point description

Maximum plasma concentration observed in blood samples taken at the following time points: 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes. The subgroup of subjects for whom pharmacokinetic samples were obtained was based on those study sites that could accommodate pharmacokinetic sampling needs.

End point type

Primary

End point timeframe

weeks 0, 12, 52

Notes
[6] - 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 are reported for pharmacokinetic analysis.
[7] - 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: Pharmacokinetic data were measured only for alglucosidase alfa, hence data were provided for this arm only.

End point values	Alglucosidase Alfa
Number of subjects analysed	32
Units: ng/mL
arithmetic mean (standard deviation)
Week 0	385237 ( 105585 )
Week 12	349269 ( 78620 )
Week 52	369744 ( 88203 )
Pooled	368083 ( 91721 )

No statistical analyses for this end point

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)

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End point title

Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax) ^[8] ^[9]

End point description

Time to maximum plasma concentration observed in blood samples taken at the following time points: 0 (before the start of the infusion), 1 and 2 hours after the start of infusion, end of the infusion, and then 0.25, 0.5, 1, 2, 3, 4, 8, 12,and 16 hours after the end of the infusion (with a 5-minute window for time-points after the start of infusion). Pooled figures combine the values for the three timeframes. The subgroup of subjects for whom pharmacokinetic samples were obtained was based on those study sites that could accommodate pharmacokinetic sampling needs.

End point type

Primary

End point timeframe

weeks 0, 12, 52

Notes
[8] - 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 are reported for pharmacokinetic analysis.
[9] - 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: Pharmacokinetic data were measured only for alglucosidase alfa, hence data were provided for this arm only.

End point values	Alglucosidase Alfa
Number of subjects analysed	32
Units: hours
arithmetic mean (standard deviation)
Week 0	3.62 ( 0.33 )
Week 12	3.62 ( 0.28 )
Week 52	3.64 ( 0.31 )
Pooled	3.63 ( 0.3 )

No statistical analyses for this end point

Secondary: Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)

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End point title

Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)

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 is 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. ITT population. Last observation carried forward.

End point type

Secondary

End point timeframe

weeks 0, 78

End point values	Alglucosidase Alfa	Placebo
Number of subjects analysed	60	30
Units: percent predicted QMT
arithmetic mean (standard deviation)
Baseline (week 0)	37.69 ( 18.88 )	32.49 ( 18.24 )
Week 78 (or last available observation)	39.05 ( 21.83 )	30.4 ( 20.54 )
Change at Week 78 from Baseline	1.22 ( 9.88 )	-2.08 ( 5.11 )

Alglucosidase Alfa vs Placebo

Statistical analysis description

The difference between alglucosidase alfa and placebo treatment groups in change in QMT from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.

Comparison groups

Alglucosidase Alfa v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1093 ^[10]

Method

ANCOVA

Parameter type

Difference

Point estimate

3.18

Confidence interval

level

95%

sides

2-sided

lower limit

-0.73

upper limit

7.08

Notes
[10] - The threshold for determining statistical significance is 0.05. No adjustment for multiple comparison was made for secondary efficacy endpoints.

Secondary: Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey

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End point title

Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey

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 Scores (PCS) report the four domains of physical functioning, role-physical, bodily pain, and general health. Higher scores are associated with better quality of life. All questions are scored on a scale from 0 to 100, with 100 representing the highest level of functioning possible. The PCS scores are reported. ITT population. Last observation carried forward.

End point type

Secondary

End point timeframe

weeks 0, 78

End point values	Alglucosidase Alfa	Placebo
Number of subjects analysed	60	30
Units: Units on a scale
arithmetic mean (standard deviation)
PCS at Baseline (week 0)	34.33 ( 8.93 )	34.91 ( 7.26 )
PCS at Week 78 (or last available observation)	35.11 ( 9.84 )	36.47 ( 9.57 )

Alglucosidase Alfa vs Placebo

Statistical analysis description

The difference between alglucosidase alfa and placebo treatment groups in change in PCS from baseline to last observation was estimated by ANCOVA after adjusting for baseline value and randomization strata.

Comparison groups

Alglucosidase Alfa v Placebo

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8333 ^[11]

Method

ANCOVA

Parameter type

Difference

Point estimate

-0.37

Confidence interval

level

95%

sides

2-sided

lower limit

-3.83

upper limit

3.09

Notes
[11] - The threshold for determining statistical significance is 0.05. No adjustment for multiple comparison was made for secondary efficacy endpoints.

Adverse events

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Timeframe for reporting adverse events

All Adverse Events (AE) were collected following the initiation of treatment (ie alglucosidase alfa or placebo) up to the end of study (0 - 78 weeks) regardless of seriousness or relationship to investigational product

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

Reporting group description

Alglucosidase alfa for 78 weeks.

Reporting group title

Placebo

Reporting group description

Placebo for 78 weeks.

Serious adverse events	Alglucosidase Alfa	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	13 / 60 (21.67%)	6 / 30 (20.00%)
number of deaths (all causes)	1	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus Fracture
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vascular disorders
Aneurysm
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (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 / 30 (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 / 30 (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 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Headache
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	1 / 1
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 / 30 (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 / 30 (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 / 30 (0.00%)
occurrences causally related to treatment / all	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Abdominal Pain Upper
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
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 / 30 (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 / 30 (0.00%)
occurrences causally related to treatment / all	1 / 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 / 30 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Septal Panniculitis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Flank Pain
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral Disc Protrusion
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (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
Diverticulitis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (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 / 30 (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 / 30 (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	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	60 / 60 (100.00%)	30 / 30 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic Naevus
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Vascular disorders
Aneurysm
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Diastolic Hypotension
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Flushing
subjects affected / exposed	3 / 60 (5.00%)	2 / 30 (6.67%)
occurrences all number	5	2
Haematoma
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Hot Flush
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Hypertension
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	3	1
Hypotension
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	1
Phlebitis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Raynaud's Phenomenon
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Vasoconstriction
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
General disorders and administration site conditions
Application Site Vesicles
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Asthenia
subjects affected / exposed	3 / 60 (5.00%)	4 / 30 (13.33%)
occurrences all number	3	8
Axillary Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Catheter Related Complication
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Catheter Site Pain
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	7	0
Catheter Site Related Reaction
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Chest Discomfort
subjects affected / exposed	6 / 60 (10.00%)	1 / 30 (3.33%)
occurrences all number	15	1
Chest Pain
subjects affected / exposed	4 / 60 (6.67%)	1 / 30 (3.33%)
occurrences all number	4	1
Chills
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	3	4
Fatigue
subjects affected / exposed	7 / 60 (11.67%)	6 / 30 (20.00%)
occurrences all number	9	14
Feeling Abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Feeling Cold
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Feeling Hot
subjects affected / exposed	3 / 60 (5.00%)	2 / 30 (6.67%)
occurrences all number	4	3
Feeling Hot And Cold
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Gait Disturbance
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Hangover
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Influenza Like Illness
subjects affected / exposed	2 / 60 (3.33%)	4 / 30 (13.33%)
occurrences all number	2	5
Infusion Site Bruising
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Infusion Site Pain
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Infusion Site Paraesthesia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Infusion Site Reaction
subjects affected / exposed	5 / 60 (8.33%)	0 / 30 (0.00%)
occurrences all number	6	0
Injection Site Phlebitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Local Swelling
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	14	2
Malaise
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	3	0
Non-Cardiac Chest Pain
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Oedema Peripheral
subjects affected / exposed	10 / 60 (16.67%)	3 / 30 (10.00%)
occurrences all number	12	5
Pain
subjects affected / exposed	5 / 60 (8.33%)	1 / 30 (3.33%)
occurrences all number	8	1
Pitting Oedema
subjects affected / exposed	2 / 60 (3.33%)	2 / 30 (6.67%)
occurrences all number	2	2
Puncture Site Haemorrhage
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Thirst
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Pyrexia
subjects affected / exposed	8 / 60 (13.33%)	8 / 30 (26.67%)
occurrences all number	8	11
Vessel Puncture Site Haematoma
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	4
Immune system disorders
Hypersensitivity
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	24	0
Reproductive system and breast disorders
Breast Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Breast Swelling
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Breast Tenderness
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Dysmenorrhoea
subjects affected / exposed	0 / 60 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	3
Fibrocystic Breast Disease
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Genital Pruritus Female
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Menstrual Discomfort
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Menstruation Irregular
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Scrotal Cyst
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Vaginal Haemorrhage
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	2
Bronchospasm
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Cough
subjects affected / exposed	6 / 60 (10.00%)	5 / 30 (16.67%)
occurrences all number	6	5
Dyspnoea
subjects affected / exposed	7 / 60 (11.67%)	4 / 30 (13.33%)
occurrences all number	10	6
Dyspnoea Exertional
subjects affected / exposed	4 / 60 (6.67%)	0 / 30 (0.00%)
occurrences all number	5	0
Epistaxis
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	8	0
Increased Bronchial Secretion
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	5
Lung Disorder
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Lung Infiltration
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Nasal Congestion
subjects affected / exposed	2 / 60 (3.33%)	2 / 30 (6.67%)
occurrences all number	2	3
Paranasal Sinus Hypersecretion
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Pharyngolaryngeal Pain
subjects affected / exposed	12 / 60 (20.00%)	5 / 30 (16.67%)
occurrences all number	19	9
Postnasal Drip
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Rales
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Respiratory Distress
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Respiratory Failure
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Respiratory Tract Congestion
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	3	0
Rhinorrhoea
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	2
Sinus Congestion
subjects affected / exposed	2 / 60 (3.33%)	3 / 30 (10.00%)
occurrences all number	2	3
Sleep Apnoea Syndrome
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Sneezing
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	2
Throat Irritation
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Throat Tightness
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Wheezing
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Psychiatric disorders
Abnormal Dreams
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Anxiety
subjects affected / exposed	2 / 60 (3.33%)	3 / 30 (10.00%)
occurrences all number	4	3
Depression
subjects affected / exposed	1 / 60 (1.67%)	2 / 30 (6.67%)
occurrences all number	3	2
Insomnia
subjects affected / exposed	6 / 60 (10.00%)	2 / 30 (6.67%)
occurrences all number	7	2
Panic Attack
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	2
Stress
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	9	0
Investigations
Alanine Aminotransferase Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Aspartate Aminotransferase Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Blood Creatine Phosphokinase Mb Increased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Blood Alkaline Phosphatase Increased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	2
Blood Folate Decreased
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Blood Glucose Increased
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Blood Parathyroid Hormone Increased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Blood Pressure Increased
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	3	2
Blood Thyroid Stimulating Hormone Increased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Blood Urine Present
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Blood Uric Acid Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Carbon Dioxide Increased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Electrocardiogram Qt Corrected Interval Prolonged
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Eosinophil Count Increased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Glucose Urine Present
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Forced Expiratory Volume Decreased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Heart Rate Irregular
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
International Normalised Ratio Decreased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Lymph Node Palpable
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Neutrophil Count Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Oxygen Saturation Decreased
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Protein Total Increased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	2
Protein Urine Present
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Specific Gravity Urine Decreased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Urine Ketone Body Present
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Vitamin D Decreased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Weight Decreased
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Weight Increased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
White Blood Cell Count Increased
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
White Blood Cells Urine Positive
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Injury, poisoning and procedural complications
Accident
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Animal Bite
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Arthropod Bite
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Arthropod Sting
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Back Injury
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Contusion
subjects affected / exposed	4 / 60 (6.67%)	6 / 30 (20.00%)
occurrences all number	6	7
Excoriation
subjects affected / exposed	0 / 60 (0.00%)	3 / 30 (10.00%)
occurrences all number	0	4
Fall
subjects affected / exposed	39 / 60 (65.00%)	20 / 30 (66.67%)
occurrences all number	154	120
Femur Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Foot Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Humerus Fracture
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Injury
subjects affected / exposed	4 / 60 (6.67%)	1 / 30 (3.33%)
occurrences all number	4	1
Injury Corneal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Joint Dislocation
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Joint Sprain
subjects affected / exposed	1 / 60 (1.67%)	2 / 30 (6.67%)
occurrences all number	1	2
Laceration
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Ligament Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Limb Crushing Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Limb Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Muscle Strain
subjects affected / exposed	4 / 60 (6.67%)	4 / 30 (13.33%)
occurrences all number	5	5
Periorbital Haematoma
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Procedural Pain
subjects affected / exposed	9 / 60 (15.00%)	3 / 30 (10.00%)
occurrences all number	11	6
Repetitive Strain Injury
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Rib Fracture
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	2	1
Road Traffic Accident
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Skeletal Injury
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Skin Laceration
subjects affected / exposed	4 / 60 (6.67%)	1 / 30 (3.33%)
occurrences all number	5	1
Tendon Injury
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Thermal Burn
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	1
Tooth Fracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Traumatic Ulcer
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Vaccination Complication
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Wound
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Cardiac disorders
Angina Pectoris
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Bundle Branch Block Left
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Bundle Branch Block Right
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Coronary Artery Disease
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Palpitations
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	9	1
Sinus Tachycardia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Tachycardia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Tricuspid Valve Incompetence
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Nervous system disorders
Areflexia
subjects affected / exposed	3 / 60 (5.00%)	2 / 30 (6.67%)
occurrences all number	4	2
Balance Disorder
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Burning Sensation
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	3	0
Carpal Tunnel Syndrome
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Disturbance In Attention
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Dizziness
subjects affected / exposed	14 / 60 (23.33%)	6 / 30 (20.00%)
occurrences all number	31	14
Dizziness Postural
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Dysgeusia
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	17
Facial Palsy
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Head Discomfort
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	4
Headache
subjects affected / exposed	24 / 60 (40.00%)	15 / 30 (50.00%)
occurrences all number	91	129
Hyperreflexia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Hypoaesthesia
subjects affected / exposed	2 / 60 (3.33%)	2 / 30 (6.67%)
occurrences all number	2	3
Hyporeflexia
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	1
Intercostal Neuralgia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Intracranial Hypotension
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Lethargy
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	4	0
Loss Of Consciousness
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	3	0
Migraine
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	5	4
Nerve Compression
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Paraesthesia
subjects affected / exposed	6 / 60 (10.00%)	4 / 30 (13.33%)
occurrences all number	16	10
Poor Quality Sleep
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Sinus Headache
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Somnolence
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	5	0
Syncope Vasovagal
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	2
Tremor
subjects affected / exposed	4 / 60 (6.67%)	0 / 30 (0.00%)
occurrences all number	4	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Lymphadenopathy
subjects affected / exposed	5 / 60 (8.33%)	0 / 30 (0.00%)
occurrences all number	6	0
Macrocytosis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Normochromic Normocytic Anaemia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Ear and labyrinth disorders
Auricular Swelling
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Ear Congestion
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Ear Discomfort
subjects affected / exposed	4 / 60 (6.67%)	1 / 30 (3.33%)
occurrences all number	23	1
Ear Pain
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	3	4
Hypoacusis
subjects affected / exposed	20 / 60 (33.33%)	7 / 30 (23.33%)
occurrences all number	22	7
Presbyacusis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Tinnitus
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	1
Tympanic Membrane Disorder
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Tympanic Membrane Scarring
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Vertigo
subjects affected / exposed	4 / 60 (6.67%)	0 / 30 (0.00%)
occurrences all number	6	0
Eye disorders
Altered Visual Depth Perception
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Asthenopia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Cataract
subjects affected / exposed	4 / 60 (6.67%)	2 / 30 (6.67%)
occurrences all number	4	2
Conjunctivitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Diplopia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Dry Eye
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Eye Irritation
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Eye Pruritus
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Lacrimation Increased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Photophobia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Vision Blurred
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	3	0
Visual Disturbance
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Vitreous Floaters
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Gastrointestinal disorders
Abdominal Discomfort
subjects affected / exposed	2 / 60 (3.33%)	2 / 30 (6.67%)
occurrences all number	2	2
Abdominal Distension
subjects affected / exposed	1 / 60 (1.67%)	2 / 30 (6.67%)
occurrences all number	1	2
Abdominal Mass
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Abdominal Pain
subjects affected / exposed	4 / 60 (6.67%)	3 / 30 (10.00%)
occurrences all number	4	3
Abdominal Pain Lower
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Abdominal Pain Upper
subjects affected / exposed	6 / 60 (10.00%)	2 / 30 (6.67%)
occurrences all number	23	3
Constipation
subjects affected / exposed	6 / 60 (10.00%)	0 / 30 (0.00%)
occurrences all number	8	0
Dental Caries
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Diarrhoea
subjects affected / exposed	18 / 60 (30.00%)	13 / 30 (43.33%)
occurrences all number	43	20
Diverticulum
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Dry Mouth
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Dyspepsia
subjects affected / exposed	5 / 60 (8.33%)	0 / 30 (0.00%)
occurrences all number	8	0
Dysphagia
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Epigastric Discomfort
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Flatulence
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Food Poisoning
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Gastrointestinal Disorder
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Gastrooesophageal Reflux Disease
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	4	0
Glossodynia
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Haematochezia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Hiatus Hernia
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Inguinal Hernia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Lip Swelling
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	3	0
Nausea
subjects affected / exposed	11 / 60 (18.33%)	10 / 30 (33.33%)
occurrences all number	38	49
Oesophageal Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Oral Mucosal Blistering
subjects affected / exposed	0 / 60 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	2
Oral Pruritus
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	2	0
Paraesthesia Oral
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Retching
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Stomach Discomfort
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	2	1
Swollen Tongue
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Toothache
subjects affected / exposed	1 / 60 (1.67%)	4 / 30 (13.33%)
occurrences all number	1	6
Vomiting
subjects affected / exposed	13 / 60 (21.67%)	3 / 30 (10.00%)
occurrences all number	16	5
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	2
Blister
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	3
Cold Sweat
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	4	0
Decubitus Ulcer
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Dermatitis Contact
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Drug Eruption
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Ecchymosis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Eczema
subjects affected / exposed	0 / 60 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	2
Erythema
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	5	1
Heat Rash
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Hyperhidrosis
subjects affected / exposed	5 / 60 (8.33%)	0 / 30 (0.00%)
occurrences all number	10	0
Ingrowing Nail
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Photosensitivity Reaction
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Pruritus
subjects affected / exposed	6 / 60 (10.00%)	1 / 30 (3.33%)
occurrences all number	15	1
Rash
subjects affected / exposed	6 / 60 (10.00%)	3 / 30 (10.00%)
occurrences all number	10	5
Rash Macular
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	5	0
Rash Maculo-Papular
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	4	0
Rash Papular
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	4	0
Rash Pruritic
subjects affected / exposed	4 / 60 (6.67%)	1 / 30 (3.33%)
occurrences all number	7	3
Skin Burning Sensation
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Skin Lesion
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Skin Nodule
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	21	0
Skin Odour Abnormal
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Skin Warm
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Subcutaneous Nodule
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Telangiectasia
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Urticaria
subjects affected / exposed	6 / 60 (10.00%)	0 / 30 (0.00%)
occurrences all number	15	0
Renal and urinary disorders
Haematuria
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	4	1
Leukocyturia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Nephrolithiasis
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	4	0
Pollakiuria
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Proteinuria
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	2
Pyuria
subjects affected / exposed	1 / 60 (1.67%)	2 / 30 (6.67%)
occurrences all number	1	2
Urinary Incontinence
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Urine Flow Decreased
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Urine Odour Abnormal
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	18 / 60 (30.00%)	9 / 30 (30.00%)
occurrences all number	27	21
Back Pain
subjects affected / exposed	14 / 60 (23.33%)	7 / 30 (23.33%)
occurrences all number	22	15
Bone Pain
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Bursitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Buttock Pain
subjects affected / exposed	3 / 60 (5.00%)	1 / 30 (3.33%)
occurrences all number	4	1
Costochondritis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Exostosis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Flank Pain
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Foot Deformity
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Groin Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Joint Range Of Motion Decreased
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Joint Swelling
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Muscle Atrophy
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Muscle Contracture
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Muscle Spasms
subjects affected / exposed	14 / 60 (23.33%)	6 / 30 (20.00%)
occurrences all number	18	7
Muscle Tightness
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	2
Muscle Twitching
subjects affected / exposed	5 / 60 (8.33%)	1 / 30 (3.33%)
occurrences all number	7	1
Muscular Weakness
subjects affected / exposed	6 / 60 (10.00%)	3 / 30 (10.00%)
occurrences all number	8	4
Musculoskeletal Chest Pain
subjects affected / exposed	5 / 60 (8.33%)	1 / 30 (3.33%)
occurrences all number	6	1
Musculoskeletal Discomfort
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Musculoskeletal Disorder
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Musculoskeletal Pain
subjects affected / exposed	8 / 60 (13.33%)	2 / 30 (6.67%)
occurrences all number	14	3
Musculoskeletal Stiffness
subjects affected / exposed	8 / 60 (13.33%)	1 / 30 (3.33%)
occurrences all number	11	1
Myalgia
subjects affected / exposed	12 / 60 (20.00%)	5 / 30 (16.67%)
occurrences all number	40	14
Neck Pain
subjects affected / exposed	7 / 60 (11.67%)	5 / 30 (16.67%)
occurrences all number	9	11
Nose Deformity
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Osteopenia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Osteoporosis
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	2	0
Pain In Extremity
subjects affected / exposed	15 / 60 (25.00%)	7 / 30 (23.33%)
occurrences all number	27	25
Plantar Fasciitis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Scoliosis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	2
Sensation Of Heaviness
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	6	1
Temporomandibular Joint Syndrome
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Tendon Pain
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Tendonitis
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	4	1
Tenosynovitis Stenosans
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Infections and infestations
Bronchitis
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	1
Cellulitis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Bronchopneumonia
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Dermatophytosis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Cystitis
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	2	2
Eye Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Folliculitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Fungal Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Fungal Skin Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Gastroenteritis
subjects affected / exposed	5 / 60 (8.33%)	1 / 30 (3.33%)
occurrences all number	5	1
Gastroenteritis Viral
subjects affected / exposed	3 / 60 (5.00%)	3 / 30 (10.00%)
occurrences all number	5	3
Gastrointestinal Infection
subjects affected / exposed	0 / 60 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	2
Genital Infection
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Gingival Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Herpes Simplex
subjects affected / exposed	4 / 60 (6.67%)	3 / 30 (10.00%)
occurrences all number	6	4
Herpes Virus Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Influenza
subjects affected / exposed	5 / 60 (8.33%)	7 / 30 (23.33%)
occurrences all number	8	8
Kidney Infection
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Laryngitis
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Localised Infection
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Mucosal Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Nasopharyngitis
subjects affected / exposed	25 / 60 (41.67%)	16 / 30 (53.33%)
occurrences all number	45	25
Otitis Media
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Postoperative Wound Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Rash Pustular
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Respiratory Tract Infection
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	3	0
Rhinitis
subjects affected / exposed	0 / 60 (0.00%)	2 / 30 (6.67%)
occurrences all number	0	2
Sinusitis
subjects affected / exposed	4 / 60 (6.67%)	4 / 30 (13.33%)
occurrences all number	5	5
Tinea Pedis
subjects affected / exposed	2 / 60 (3.33%)	0 / 30 (0.00%)
occurrences all number	4	0
Tonsillitis
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Tooth Infection
subjects affected / exposed	2 / 60 (3.33%)	1 / 30 (3.33%)
occurrences all number	2	1
Upper Respiratory Tract Infection
subjects affected / exposed	11 / 60 (18.33%)	3 / 30 (10.00%)
occurrences all number	16	3
Urinary Tract Infection
subjects affected / exposed	5 / 60 (8.33%)	4 / 30 (13.33%)
occurrences all number	6	7
Vaginal Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	4	0
Viral Infection
subjects affected / exposed	2 / 60 (3.33%)	2 / 30 (6.67%)
occurrences all number	2	2
Vulvovaginal Mycotic Infection
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Wound Infection
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Metabolism and nutrition disorders
Decreased Appetite
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Diabetes Mellitus Non-Insulin-Dependent
subjects affected / exposed	0 / 60 (0.00%)	1 / 30 (3.33%)
occurrences all number	0	1
Hyperglycaemia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Hypernatraemia
subjects affected / exposed	1 / 60 (1.67%)	1 / 30 (3.33%)
occurrences all number	1	1
Hypertriglyceridaemia
subjects affected / exposed	1 / 60 (1.67%)	0 / 30 (0.00%)
occurrences all number	1	0
Hypokalaemia
subjects affected / exposed	3 / 60 (5.00%)	0 / 30 (0.00%)
occurrences all number	5	0

More information

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Were there any global substantial amendments to the protocol? Yes

15 Sep 2005

- Subjects who transferred to regional investigational sites after 6 months of treatment could complete the remaining infusion visits at the transfer site. The Week 38 and Week 52 or early withdrawal infusions were no longer required to be done at the primary site. - Conduct of the 6MWT at Screening/Baseline was changed from 2 tests performed on the same day to testing on 2 consecutive days. - Inclusion criterion, which required the subject to have a forced expiratory volume in the first second of the FVC maneuver (FEV1)/FVC value of 70% predicted in the upright position, was deleted. The purpose of this criterion was to identify subjects with confounding obstructive disease that was NOT related to Pompe disease. However, weakness in the supporting respiratory muscles could prevent subjects from exhaling sufficient volume in the first second of the FVC maneuver (FEV1), causing what appears to be mild obstructive involvement in addition to the restrictive involvement caused by diaphragmatic weakness. - Exclusion for major congenital anomaly was limited to those that in the judgment of the Investigator would significantly interfere with study compliance, including all prescribed evaluations and follow-up activities.

26 May 2006

- The infusion rate schedule was adjusted to a maximum rate of approximately 7 mg/kg/hr to assist in Infusion-associated reaction (IAR) management, consistent with infantile-onset studies of Pompe disease conducted by Genzyme. In Protocol Amendment 3, this infusion rate schedule was subsequently designated as “recommended” to allow investigator discretion in setting the infusion rate.

16 Aug 2006

- The infusion rate schedule as adjusted in Amendment 2 was designated as “recommended” to allow investigator discretion in setting the infusion rate. -It proposed an adaptive, information-based design.

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:
Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy and Pharmacokinetics of Myozyme in Patients With Late-Onset Pompe Disease.

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

Primary: Summary of Subjects Reporting Treatment-Emergent Adverse Events

Primary: Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline

Primary: Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline

Primary: Percent of Predicted Forced Vital Capacity (FVC)

Primary: Percent of Predicted Forced Vital Capacity (FVC)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)

Secondary: Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)

Secondary: Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)

Secondary: Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey

Secondary: Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical trials

Clinical Trial Results: Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy and Pharmacokinetics of Myozyme in Patients With Late-Onset Pompe Disease.

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

Primary: Summary of Subjects Reporting Treatment-Emergent Adverse Events

Primary: Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline

Primary: Mean Distance Walked as Measured by Six-minute Walk Test (6MWT) at Weeks 0 and 78, and Mean Change From Baseline

Primary: Percent of Predicted Forced Vital Capacity (FVC)

Primary: Percent of Predicted Forced Vital Capacity (FVC)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Area Under the Curve (AUC)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Maximum Plasma Concentration(Cmax)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)

Primary: Recombinant Human Acid Alpha-Glucosidase (rhGAA) Pharmacokinetic Parameters: Mean Time to Maximum Plasma Concentration(Tmax)

Secondary: Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)

Secondary: Percent Predicted Proximal Muscle Strength of the Lower Limbs as Measured by Quantitative Muscle Testing (QMT)

Secondary: Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey

Secondary: Health-related Quality of Life Survey Values Related to Physical Components as Measured by the Medical Outcomes Study (MOS) Short Form-36 Health Survey

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Efficacy and Pharmacokinetics of Myozyme in Patients With Late-Onset Pompe Disease.