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Clinical Trial Results:
Prospective, double-blind, placebo-controlled, randomized, multi-center study with an open-label extension period to investigate the efficacy and safety of NT 201 in the treatment of post-stroke spasticity of the upper limb

Summary
EudraCT number	2010-023043-15
Trial protocol	DE HU CZ
Global end of trial date	13 Feb 2014

Results information
Results version number	v1(current)
This version publication date	18 Feb 2016
First version publication date	29 Jul 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

MRZ 60201/SP/3001

ISRCTN number

US NCT number

NCT01392300

WHO universal trial number (UTN)

Sponsor organisation name

Merz Pharmaceuticals GmbH

Sponsor organisation address

Eckenheimer Landstrasse 100, Frankfurt/Main, Germany, 60318

Public contact

Public Disclosure Manager, Merz Pharmaceuticals GmbH, clinicaltrials@merz.de

Scientific contact

Public Disclosure Manager, Merz Pharmaceuticals GmbH, clinicaltrials@merz.de

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?

Analysis stage

Final

Date of interim/final analysis

20 Aug 2013

Is this the analysis of the primary completion data?

Yes

Primary completion date

21 Mar 2013

Global end of trial reached?

Yes

Global end of trial date

13 Feb 2014

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to determine whether injections of Botulinum toxin type A into muscles of the upper limb are effective in treating spasticity in patients after stroke.

Protection of trial subjects

High medical and ethical standards were followed in accordance with Good Clinical Practice and other applicable regulations. In addition, an independent data monitoring committee was in charge of monitoring patient safety while the study was ongoing.

Background therapy

Physiotherapy, occupational therapy, and other rehabilitation measures to treat spasticity.

Evidence for comparator

Actual start date of recruitment

02 Sep 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 104

Country: Number of subjects enrolled

Czech Republic: 71

Country: Number of subjects enrolled

India: 39

Country: Number of subjects enrolled

United States: 38

Country: Number of subjects enrolled

Hungary: 32

Country: Number of subjects enrolled

Russian Federation: 32

Country: Number of subjects enrolled

Germany: 1

Worldwide total number of subjects

317

EEA total number of subjects

208

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)

237

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

349 subjects were screened, of whom 26 did not meet study entry criteria, and 6 withdrew their consent

Period 1 title

Main Period (MP)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)

Arm description

IncobotulinumtoxinA (Xeomin) (400 Units): Main period, one injection session - double-blind, randomized treatment assignment

Arm type

Experimental

Investigational medicinal product name

IncobotulinumtoxinA (400 U)

Investigational medicinal product code

NT 201

Other name

Xeomin, Bocouture, Botulinum toxin type A (150 kiloDalton) free from complexing proteins

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

400 U total dose per injection session, to be administered by guided (EMG, E-Stim) intramuscular injections. In the double-blind period, a primary target clinical pattern (PTCP, flexed elbow, flexed wrist or clenched fist) was selected for each patient by the investigator and treated with a predefined fixed dose (flexed elbow, 200 U; flexed wrist, 150 U; or clenched fist, 100 U). Doses and injection sites for other muscles were flexible within pre-defined ranges, based on patients’ individual conditions, and on approved (in the EU) dose ranges for individual muscles.

Double-blind Placebo Comparator

Arm description

Placebo to incobotulinumtoxinA (Xeomin) (400 Units): Main period, one injection session - double-blind, randomized treatment assignment

Arm type

Placebo

Investigational medicinal product name

Placebo to incobotulinumtoxinA (Xeomin) powder for solution for injection

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Volume equivalent to 400 U total dose per injection session, to be administered by guided (EMG, E-Stim) intramuscular injections. In the double-blind period, a primary target clinical pattern (PTCP, flexed elbow, flexed wrist or clenched fist) was selected for each patient by the investigator and treated with a predefined fixed dose (flexed elbow, 200 U; flexed wrist, 150 U; or clenched fist, 100 U). Doses and injection sites for other muscles were flexible within pre-defined ranges, based on patients' individual conditions, and on approved (in the EU) dose ranges for individual muscles.

Number of subjects in period 1	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Started	210	107
Completed	199	100
Not completed	11	7
Consent withdrawn by subject	5	1
Non-compliance	1	-
Lost to follow-up	3	3
Predefined discontinuation criteria	2	3

Period 2 title

Open Label Extension (OLEX) Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

OLEX IncobotulinumtoxinA (Xeomin) (400 units, 3 Injections)

Arm description

IncobotulinumtoxinA (Xeomin) (400 Units): OLEX period, three injection sessions - open-label treatment assignment

Arm type

Experimental

Investigational medicinal product name

IncobotulinumtoxinA (400 U)

Investigational medicinal product code

NT 201

Other name

Xeomin, Bocouture, Botulinum toxin type A (150 kiloDalton) free from complexing proteins

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

400 U total dose per injection session, to be administered by guided (EMG, E-Stim) intramuscular injections to elbow flexor, forearm pronator, wrist flexor, finger flexor and thumb flexor muscles. In the open-label extension period, doses and injection sites were flexible within pre-defined ranges, based on patients’ individual condition and on approved (in the EU) dose ranges for individual muscles.

Number of subjects in period 2	OLEX IncobotulinumtoxinA (Xeomin) (400 units, 3 Injections)
Started	299
Week 24	283
Week 36	259
Completed	248
Not completed	51
Adverse event, serious fatal	4
Consent withdrawn by subject	17
Adverse event, non-fatal	7
Non-compliance	1
Lost to follow-up	6
Protocol deviation	13
Lack of efficacy	3

Baseline characteristics

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Reporting group title

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)

Reporting group description

IncobotulinumtoxinA (Xeomin) (400 Units): Main period, one injection session - double-blind, randomized treatment assignment

Reporting group title

Double-blind Placebo Comparator

Reporting group description

Placebo to incobotulinumtoxinA (Xeomin) (400 Units): Main period, one injection session - double-blind, randomized treatment assignment

Reporting group values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator	Total
Number of subjects	210	107	317
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	0	0	0
Adolescents (12-17 years)	0	0	0
Adults (18-64 years)	162	75	237
From 65-84 years	48	32	80
85 years and over	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	55.3 ± 11.9	57.8 ± 10.9	-
Gender, Male/Female
Units: participants
Female	120	61	181
Male	90	46	136
Ethnicity (NIH/OMB)
Units: Subjects
Hispanic or Latino	4	0	4
Not Hispanic or Latino	22	12	34
Unknown or Not Reported	184	95	279
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0
Asian	27	13	40
Native Hawaiian or Other Pacific Islander	1	0	1
Black or African American	6	3	9
White	175	91	266
More than one race	0	0	0
Unknown or Not Reported	1	0	1
Region of Enrollment
Units: Subjects
United States	26	12	38
Czech Republic	46	25	71
Hungary	23	9	32
Poland	66	38	104
Russian Federation	22	10	32
Germany	1	0	1
India	26	13	39

End points

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Reporting group title

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)

Reporting group description

IncobotulinumtoxinA (Xeomin) (400 Units): Main period, one injection session - double-blind, randomized treatment assignment

Reporting group title

Double-blind Placebo Comparator

Reporting group description

Placebo to incobotulinumtoxinA (Xeomin) (400 Units): Main period, one injection session - double-blind, randomized treatment assignment

Reporting group title

OLEX IncobotulinumtoxinA (Xeomin) (400 units, 3 Injections)

Reporting group description

IncobotulinumtoxinA (Xeomin) (400 Units): OLEX period, three injection sessions - open-label treatment assignment

Subject analysis set title

Full Analysis Set

Subject analysis set type

Full analysis

Subject analysis set description

All subjects who were randomized after the Amended Protocol Version 3.0 (dated 11-MAY-2012) became effective, who were treated, and for whom at least an AS baseline value for the primary target clinical pattern was given.

Primary: Change from baseline in Ashworth Scale (AS) Score of primary target clinical pattern

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End point title

Change from baseline in Ashworth Scale (AS) Score of primary target clinical pattern

End point description

Primary target clinical pattern was defined by investigator for each subject at baseline visit and was either flexed wrist or clenched fist or flexed elbow. The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension).

End point type

Primary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.9 ± 0.06	-0.5 ± 0.08

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.5

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

-0.3

Variability estimate

Standard error of the mean

Dispersion value

0.1

Primary: Investigator's Global Impression of Change

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End point title

Investigator's Global Impression of Change

End point description

This is the co-primary outcome measure. The Global Impression of Change Scale [GICS] is used to measure the investigator's impression of change due to treatment. The response option is a common 7-point Likert scale that ranges from -3 = very much worse to +3 = very much improved.

End point type

Primary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	1.2 ± 0.07	0.9 ± 0.09

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.003

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

0.3

Confidence interval

level

95%

sides

2-sided

lower limit

0.1

upper limit

0.5

Variability estimate

Standard error of the mean

Dispersion value

0.11

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the primary target clinical pattern

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End point title

Response rates on the Ashworth Scale at week 4 calculated for the primary target clinical pattern

End point description

Primary target clinical pattern was defined by investigator for each subject at baseline visit and was either flexed wrist or clenched fist or flexed elbow. Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis.

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	119	33

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

4.28

Confidence interval

level

95%

sides

2-sided

lower limit

2.43

upper limit

7.52

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the primary target clinical pattern

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End point title

Response rates on the Ashworth Scale at week 8 calculated for the primary target clinical pattern

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	104	34

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.69

Confidence interval

level

95%

sides

2-sided

lower limit

1.56

upper limit

4.63

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the primary target clinical pattern

Top of page

End point title

Response rates on the Ashworth Scale at week 12 calculated for the primary target clinical pattern

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	68	22

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.004

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.48

Confidence interval

level

95%

sides

2-sided

lower limit

1.33

upper limit

4.61

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group flexed wrist

Top of page

End point title

Response rates on the Ashworth Scale at week 4 calculated for the muscle group flexed wrist

End point description

The Ashworth Scale is well known and commonly used in clinical trials with spasticity. It was used to categorize severity of spasticity by judging resistance to passive movement. It is a 5-point scale that ranges from 0 (=no increase in tone) to 4 (=limb rigid in flexion or extension). Subjects with a reduction of one point were defined as responder for the aim of the efficacy analysis.

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	102	31

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.13

Confidence interval

level

95%

sides

2-sided

lower limit

1.76

upper limit

5.57

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group flexed wrist

Top of page

End point title

Response rates on the Ashworth Scale at week 8 calculated for the muscle group flexed wrist

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	90	33

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.021

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.92

Confidence interval

level

95%

sides

2-sided

lower limit

1.1

upper limit

3.34

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group flexed wrist

Top of page

End point title

Response rates on the Ashworth Scale at week 12 calculated for the muscle group flexed wrist

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	59	17

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.58

Confidence interval

level

95%

sides

2-sided

lower limit

1.32

upper limit

5.05

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group flexed elbow

Top of page

End point title

Response rates on the Ashworth Scale at week 4 calculated for the muscle group flexed elbow

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	99	28

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.72

Confidence interval

level

95%

sides

2-sided

lower limit

2.06

upper limit

6.72

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group flexed elbow

Top of page

End point title

Response rates on the Ashworth Scale at week 8 calculated for the muscle group flexed elbow

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	85	28

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.5

Confidence interval

level

95%

sides

2-sided

lower limit

1.4

upper limit

4.46

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group flexed elbow

Top of page

End point title

Response rates on the Ashworth Scale at week 12 calculated for the muscle group flexed elbow

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	52	21

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.102

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.9

upper limit

3.22

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group clenched fist

Top of page

End point title

Response rates on the Ashworth Scale at week 4 calculated for the muscle group clenched fist

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	90	26

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.95

Confidence interval

level

95%

sides

2-sided

lower limit

1.67

upper limit

5.23

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group clenched fist

Top of page

End point title

Response rates on the Ashworth Scale at week 8 calculated for the muscle group clenched fist

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	82	27

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.002

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.46

Confidence interval

level

95%

sides

2-sided

lower limit

1.37

upper limit

4.41

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group clenched fist

Top of page

End point title

Response rates on the Ashworth Scale at week 12 calculated for the muscle group clenched fist

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	49	19

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.069

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.87

Confidence interval

level

95%

sides

2-sided

lower limit

0.95

upper limit

3.69

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group thumb-in-palm

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End point title

Response rates on the Ashworth Scale at week 4 calculated for the muscle group thumb-in-palm

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	56	21

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.034

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.05

Confidence interval

level

95%

sides

2-sided

lower limit

1.05

upper limit

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group thumb-in-palm

Top of page

End point title

Response rates on the Ashworth Scale at week 8 calculated for the muscle group thumb-in-palm

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	52	23

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.169

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.61

Confidence interval

level

95%

sides

2-sided

lower limit

0.82

upper limit

3.16

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group thumb-in-palm

Top of page

End point title

Response rates on the Ashworth Scale at week 12 calculated for the muscle group thumb-in-palm

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	35	20

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.92

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.04

Confidence interval

level

95%

sides

2-sided

lower limit

0.49

upper limit

2.18

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group pronated forearm

Top of page

End point title

Response rates on the Ashworth Scale at week 4 calculated for the muscle group pronated forearm

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	73	19

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

3.56

Confidence interval

level

95%

sides

2-sided

lower limit

1.83

upper limit

6.91

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group pronated forearm

Top of page

End point title

Response rates on the Ashworth Scale at week 8 calculated for the muscle group pronated forearm

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	64	20

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.41

Confidence interval

level

95%

sides

2-sided

lower limit

1.28

upper limit

4.56

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group pronated forearm

Top of page

End point title

Response rates on the Ashworth Scale at week 12 calculated for the muscle group pronated forearm

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: participants
number (not applicable)	51	15

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

2.26

Confidence interval

level

95%

sides

2-sided

lower limit

1.15

upper limit

4.41

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group flexed wrist.

Top of page

End point title

Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group flexed wrist.

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.8 ± 0.06	-0.5 ± 0.08

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.1

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group flexed wrist.

Top of page

End point title

Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group flexed wrist.

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.6 ± 0.06	-0.4 ± 0.08

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.011

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.09

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group flexed wrist.

Top of page

End point title

Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group flexed wrist.

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.3 ± 0.05	-0.1 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.032

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group flexed elbow.

Top of page

End point title

Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group flexed elbow.

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.7 ± 0.05	-0.3 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group flexed elbow.

Top of page

End point title

Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group flexed elbow.

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.6 ± 0.05	-0.3 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.09

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group flexed elbow.

Top of page

End point title

Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group flexed elbow.

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.05	-0.2 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.029

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group clenched fist.

Top of page

End point title

Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group clenched fist.

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.7 ± 0.06	-0.3 ± 0.08

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.09

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group clenched fist.

Top of page

End point title

Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group clenched fist.

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.6 ± 0.05	-0.4 ± 0.08

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.019

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.09

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group clenched fist.

Top of page

End point title

Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group clenched fist.

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.3 ± 0.05	-0.1 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.137

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group thumb-in-palm.

Top of page

End point title

Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group thumb-in-palm.

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.05	-0.2 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.013

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.09

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group thumb-in-palm.

Top of page

End point title

Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group thumb-in-palm.

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.3 ± 0.05	-0.2 ± 0.08

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.131

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.09

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group thumb-in-palm.

Top of page

End point title

Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group thumb-in-palm.

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.2 ± 0.05	-0.1 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.714

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group pronated forearm.

Top of page

End point title

Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group pronated forearm.

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.5 ± 0.05	-0.2 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

-0.2

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group pronated forearm.

Top of page

End point title

Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group pronated forearm.

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.05	-0.2 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.008

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.09

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group pronated forearm.

Top of page

End point title

Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group pronated forearm.

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.3 ± 0.05	-0.1 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.062

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to Week 4 in Disability Assessment Scale - principal therapeutic target domain

Top of page

End point title

Changes from baseline to Week 4 in Disability Assessment Scale - principal therapeutic target domain

End point description

The Disability Assessment Scale consists of the four domains hygiene, dressing, limb position, and pain which were assessed on a 4-point scale with the values 0 (=no disability), 1 (=mild disability), 2 (=moderate disability), and 3 (=severe disability).

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.5 ± 0.05	-0.3 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.006

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to Week 8 in Disability Assessment Scale - principal therapeutic target domain

Top of page

End point title

Changes from baseline to Week 8 in Disability Assessment Scale - principal therapeutic target domain

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.5 ± 0.05	-0.3 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.076

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to Week 12 in Disability Assessment Scale - principal therapeutic target domain

Top of page

End point title

Changes from baseline to Week 12 in Disability Assessment Scale - principal therapeutic target domain

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.05	-0.4 ± 0.06

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.416

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to Week 4 in Disability Assessment Scale - domain hygiene

Top of page

End point title

Changes from baseline to Week 4 in Disability Assessment Scale - domain hygiene

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.05	-0.1 ± 0.06

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.001

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.07

Secondary: Changes from baseline to Week 8 in Disability Assessment Scale - domain hygiene

Top of page

End point title

Changes from baseline to Week 8 in Disability Assessment Scale - domain hygiene

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.05	-0.2 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.175

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to Week 12 in Disability Assessment Scale - domain hygiene

Top of page

End point title

Changes from baseline to Week 12 in Disability Assessment Scale - domain hygiene

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.3 ± 0.05	-0.1 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.14

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to Week 4 in Disability Assessment Scale - domain dressing

Top of page

End point title

Changes from baseline to Week 4 in Disability Assessment Scale - domain dressing

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.05	-0.2 ± 0.06

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.007

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

-0.1

Variability estimate

Standard error of the mean

Dispersion value

0.07

Secondary: Changes from baseline to Week 8 in Disability Assessment Scale - domain dressing

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End point title

Changes from baseline to Week 8 in Disability Assessment Scale - domain dressing

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.05	-0.2 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.018

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to Week 12 in Disability Assessment Scale - domain dressing

Top of page

End point title

Changes from baseline to Week 12 in Disability Assessment Scale - domain dressing

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.3 ± 0.04	-0.1 ± 0.06

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.105

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.3

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.07

Secondary: Changes from baseline to Week 4 in Disability Assessment Scale - domain limb position

Top of page

End point title

Changes from baseline to Week 4 in Disability Assessment Scale - domain limb position

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.5 ± 0.05	-0.3 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.016

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to Week 8 in Disability Assessment Scale - domain limb position

Top of page

End point title

Changes from baseline to Week 8 in Disability Assessment Scale - domain limb position

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.05	-0.2 ± 0.07

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.014

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.4

upper limit

Variability estimate

Standard error of the mean

Dispersion value

0.08

Secondary: Changes from baseline to Week 12 in Disability Assessment Scale - domain limb position

Top of page

End point title

Changes from baseline to Week 12 in Disability Assessment Scale - domain limb position

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.4 ± 0.05	-0.3 ± 0.06

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.22

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.07

Secondary: Changes from baseline to Week 4 in Disability Assessment Scale - domain pain

Top of page

End point title

Changes from baseline to Week 4 in Disability Assessment Scale - domain pain

End point description

End point type

Secondary

End point timeframe

Week 4

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.2 ± 0.06	-0.2 ± 0.08

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.429

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.1

Variability estimate

Standard error of the mean

Dispersion value

0.09

Secondary: Changes from baseline to Week 8 in Disability Assessment Scale - domain pain

Top of page

End point title

Changes from baseline to Week 8 in Disability Assessment Scale - domain pain

End point description

End point type

Secondary

End point timeframe

Week 8

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.2 ± 0.06	-0.2 ± 0.08

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.884

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.09

Secondary: Changes from baseline to Week 12 in Disability Assessment Scale - domain pain

Top of page

End point title

Changes from baseline to Week 12 in Disability Assessment Scale - domain pain

End point description

End point type

Secondary

End point timeframe

Week 12

End point values	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator
Number of subjects analysed	171	88
Units: units on a scale
least squares mean (standard error)	-0.3 ± 0.06	-0.2 ± 0.09

STATISTICAL_ANALYSIS_TITLE

Comparison groups

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units) v Double-blind Placebo Comparator

Number of subjects included in analysis

259

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.844

Method

ANCOVA

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.2

upper limit

0.2

Variability estimate

Standard error of the mean

Dispersion value

0.1

Adverse events

Top of page

Timeframe for reporting adverse events

From the timepoint of first injection until 12 weeks +/- 3 days after last injection

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)

Reporting group description

IncobotulinumtoxinA (Xeomin) (400 Units): Main period, one injection session - double-blind, randomized treatment assignment

Reporting group title

Double-blind Placebo Comparator

Reporting group description

Placebo to incobotulinumtoxinA (Xeomin) (400 Units): Main period, one injection session - double-blind, randomized treatment assignment

Reporting group title

OLEX IncobotulinumtoxinA (Xeomin) (400 Units, 3 injections)

Reporting group description

IncobotulinumtoxinA (Xeomin) (400 Units): OLEX period, three injection sessions - open-label treatment assignment

Serious adverse events	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator	OLEX IncobotulinumtoxinA (Xeomin) (400 Units, 3 injections)
Total subjects affected by serious adverse events
subjects affected / exposed	7 / 210 (3.33%)	2 / 107 (1.87%)	22 / 296 (7.43%)
number of deaths (all causes)	0	0	4
number of deaths resulting from adverse events	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
subjects affected / exposed	0 / 210 (0.00%)	1 / 107 (0.93%)	0 / 296 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ovarian adenoma
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Vascular disorders
Peripheral ischaemia
subjects affected / exposed	2 / 210 (0.95%)	0 / 107 (0.00%)	0 / 296 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Deep vein thrombosis
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hypertension
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Cardiac death
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Femoral neck fracture
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Femur fracture
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cardiac disorders
Acute myocardial infarction
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Nervous system disorders
Epilepsy
subjects affected / exposed	1 / 210 (0.48%)	0 / 107 (0.00%)	2 / 296 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cerebral haemorrhage
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Ischaemic stroke
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pseudobulbar palsy
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Eye disorders
Glaucoma
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Pancreatic enlargement
subjects affected / exposed	1 / 210 (0.48%)	0 / 107 (0.00%)	0 / 296 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Pancreatitis acute
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	1 / 210 (0.48%)	0 / 107 (0.00%)	0 / 296 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Calculus bladder
subjects affected / exposed	0 / 210 (0.00%)	1 / 107 (0.93%)	0 / 296 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Dysuria
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Infections and infestations
Pneumonia
subjects affected / exposed	1 / 210 (0.48%)	0 / 107 (0.00%)	2 / 296 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 210 (0.48%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	1 / 210 (0.48%)	0 / 107 (0.00%)	0 / 296 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1
Endocarditis
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0
Septic shock
subjects affected / exposed	0 / 210 (0.00%)	0 / 107 (0.00%)	1 / 296 (0.34%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	Double-blind IncobotulinumtoxinA (Xeomin) (400 Units)	Double-blind Placebo Comparator	OLEX IncobotulinumtoxinA (Xeomin) (400 Units, 3 injections)
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 210 (2.86%)	4 / 107 (3.74%)	32 / 296 (10.81%)
Investigations
Blood glucose increased
subjects affected / exposed	1 / 210 (0.48%)	0 / 107 (0.00%)	8 / 296 (2.70%)
occurrences all number	1	0	9
International normalised ratio increased
subjects affected / exposed	1 / 210 (0.48%)	0 / 107 (0.00%)	8 / 296 (2.70%)
occurrences all number	1	0	10
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 210 (0.00%)	1 / 107 (0.93%)	7 / 296 (2.36%)
occurrences all number	0	1	9
Nervous system disorders
Headache
subjects affected / exposed	1 / 210 (0.48%)	3 / 107 (2.80%)	3 / 296 (1.01%)
occurrences all number	1	6	6
Epilepsy
subjects affected / exposed	5 / 210 (2.38%)	0 / 107 (0.00%)	6 / 296 (2.03%)
occurrences all number	6	0	8

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

06 Mar 2012

The amendment specified changes in the study inclusion criteria, selection of primary target pattern, instructions for administration and dosing of NT 201, study assessments and co-primary endpoint and statistical methods to reflect FDA comments and to demonstrate the improvement of spasticity throughout the upper limb with NT 201 treatment accordingly.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
30 Jan 2012	The original protocol was altered by a single major amendment, prompted by comments received in January 2012 from the US Food and Drug Administration following a special protocol assessment. As patient recruitment for this study had already started (in September 2011) and 58 subjects had already been enrolled, recruitment of further patients was set on temporary hold to allow implementation of the comments into the study protocol.	17 Apr 2012

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: Prospective, double-blind, placebo-controlled, randomized, multi-center study with an open-label extension period to investigate the efficacy and safety of NT 201 in the treatment of post-stroke spasticity of the upper limb

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change from baseline in Ashworth Scale (AS) Score of primary target clinical pattern

Primary: Change from baseline in Ashworth Scale (AS) Score of primary target clinical pattern

Primary: Investigator's Global Impression of Change

Primary: Investigator's Global Impression of Change

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the primary target clinical pattern

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the primary target clinical pattern

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the primary target clinical pattern

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the primary target clinical pattern

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the primary target clinical pattern

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the primary target clinical pattern

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group flexed wrist

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group flexed wrist

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group flexed wrist

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group flexed wrist

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group flexed wrist

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group flexed wrist

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group flexed elbow

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group flexed elbow

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group flexed elbow

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group flexed elbow

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group flexed elbow

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group flexed elbow

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group clenched fist

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group clenched fist

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group clenched fist

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group clenched fist

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group clenched fist

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group clenched fist

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group thumb-in-palm

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group thumb-in-palm

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group thumb-in-palm

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group thumb-in-palm

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group thumb-in-palm

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group thumb-in-palm

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group pronated forearm

Secondary: Response rates on the Ashworth Scale at week 4 calculated for the muscle group pronated forearm

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group pronated forearm

Secondary: Response rates on the Ashworth Scale at week 8 calculated for the muscle group pronated forearm

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group pronated forearm

Secondary: Response rates on the Ashworth Scale at week 12 calculated for the muscle group pronated forearm

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group flexed wrist.

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group flexed wrist.

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group flexed wrist.

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group flexed wrist.

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group flexed wrist.

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group flexed wrist.

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group flexed elbow.

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group flexed elbow.

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group flexed elbow.

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group flexed elbow.

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group flexed elbow.

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group flexed elbow.

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group clenched fist.

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group clenched fist.

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group clenched fist.

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group clenched fist.

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group clenched fist.

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group clenched fist.

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group thumb-in-palm.

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group thumb-in-palm.

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group thumb-in-palm.

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group thumb-in-palm.

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group thumb-in-palm.

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group thumb-in-palm.

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group pronated forearm.

Secondary: Changes from baseline to week 4 in Ashworth Scale Score for treated muscle group pronated forearm.

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group pronated forearm.

Secondary: Changes from baseline to week 8 in Ashworth Scale Score for treated muscle group pronated forearm.

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group pronated forearm.

Secondary: Changes from baseline to week 12 in Ashworth Scale Score for treated muscle group pronated forearm.

Clinical Trial Results:
Prospective, double-blind, placebo-controlled, randomized, multi-center study with an open-label extension period to investigate the efficacy and safety of NT 201 in the treatment of post-stroke spasticity of the upper limb