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Clinical Study to Investigate the Efficacy and Safety of Two Dose Levels of NT 201 Versus Placebo in Treating Chronic Troublesome Sialorrhea in Various Neurological Conditions (SIAXI)

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ClinicalTrials.gov Identifier: NCT02091739
Recruitment Status : Completed
First Posted : March 19, 2014
Results First Posted : February 15, 2018
Last Update Posted : March 27, 2018
Sponsor:
Information provided by (Responsible Party):
Merz Pharmaceuticals GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Chronic Troublesome Sialorrhea
Parkinson's Disease
Post-stroke
Traumatic Brain Injury
Interventions Drug: IncobotulinumtoxinA (100 Units)
Drug: IncobotulinumtoxinA (75 Units)
Drug: Placebo
Enrollment 184
Recruitment Details The study was conducted at 12 sites in Poland and Germany.
Pre-assignment Details A total of 216 participants were screened for the study, of which 184 participants were randomized and treated in the Main Period (MP) of the study. A total of 173 participants who completed the MP, entered the 2 treatment arms of the Extension Period (EP) of the study.
Arm/Group Title Placebo MP: IncobotulinumtoxinA (Xeomin) (75 Units) MP: IncobotulinumtoxinA (Xeomin) (100 Units) EP: IncobotulinumtoxinA (Xeomin) (75 Units) EP: IncobotulinumtoxinA (Xeomin) (100 Units)
Hide Arm/Group Description Participants received one injection session of overall 2.0 milliliter (mL) placebo matched to the volume of incobotulinumtoxinA via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP. Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 75 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP. Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 100 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP. Participants received overall 2.0 mL incobotulinumtoxinA containing 75 units via bilateral intraglandular injection into the parotid and submandibular glands at each of the three injection sessions in the EP. Participants received overall 2.0 mL incobotulinumtoxinA containing 100 units via bilateral intraglandular injection into the parotid and submandibular glands at each of the three injection sessions in the EP.
Period Title: MP: 16 Weeks
Started 36 74 74 0 0
Completed 32 69 72 0 0
Not Completed 4 5 2 0 0
Reason Not Completed
Adverse Event             1             1             1             0             0
Withdrawal by Subject             3             4             0             0             0
Lost to Follow-up             0             0             1             0             0
Period Title: EP: 48 Weeks
Started 0 0 0 84 89
Completed [1] 0 0 0 76 75
Not Completed 0 0 0 8 14
Reason Not Completed
Other             0             0             0             1             0
Death             0             0             0             3             2
Adverse Event             0             0             0             2             6
Withdrawal by Subject             0             0             0             2             6
[1]
Participants who completed the MP (n=173), entered the 2 treatment arms of the EP of the study.
Arm/Group Title MP: Placebo MP: IncobotulinumtoxinA (Xeomin) (75 Units) MP: IncobotulinumtoxinA (Xeomin) (100 Units) Total
Hide Arm/Group Description Participants received one injection session of overall 2.0 mL placebo matched to the volume of incobotulinumtoxinA via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP. Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 75 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP. Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 100 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP. Total of all reporting groups
Overall Number of Baseline Participants 36 74 74 184
Hide Baseline Analysis Population Description
The Full analysis set (FAS) is the subset of participants who were treated and had at least the baseline value of unstimulated salivary flow (uSFR).
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 74 participants 74 participants 184 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
19
  52.8%
30
  40.5%
28
  37.8%
77
  41.8%
>=65 years
17
  47.2%
44
  59.5%
46
  62.2%
107
  58.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 74 participants 74 participants 184 participants
Female
8
  22.2%
24
  32.4%
22
  29.7%
54
  29.3%
Male
28
  77.8%
50
  67.6%
52
  70.3%
130
  70.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 74 participants 74 participants 184 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
   1.4%
1
   0.5%
Not Hispanic or Latino
36
 100.0%
74
 100.0%
73
  98.6%
183
  99.5%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 74 participants 74 participants 184 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
1
   1.4%
1
   0.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
36
 100.0%
74
 100.0%
73
  98.6%
183
  99.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 36 participants 74 participants 74 participants 184 participants
80.6  (16.4) 78.4  (17.1) 79.8  (14) 79.4  (15.7)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 36 participants 74 participants 74 participants 184 participants
28.5  (6) 26.7  (5.2) 27.7  (3.8) 27.5  (4.9)
1.Primary Outcome
Title MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 4
Hide Description uSFR was assessed by weighing of dental rolls soaked with saliva over 5 minutes and then procedure was repeated after 30 minutes and the average of the 2 results for flow rate was calculated.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis covers all participants from FAS who have at least one post-baseline uSFR assessment. The FAS is the subset of participants who were treated and had at least the baseline value of uSFR.
Arm/Group Title MP: Placebo MP: IncobotulinumtoxinA (Xeomin) (75 Units) MP: IncobotulinumtoxinA (Xeomin) (100 Units)
Hide Arm/Group Description:
Participants received one injection session of overall 2.0 mL placebo matched to the volume of incobotulinumtoxinA via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 75 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 100 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Overall Number of Participants Analyzed 36 73 73
Least Squares Mean (Standard Error)
Unit of Measure: gram per minute (g/min)
-0.04  (0.033) -0.06  (0.027) -0.13  (0.026)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MP: Placebo, MP: IncobotulinumtoxinA (Xeomin) (100 Units)
Comments

A fixed sequence test procedure was used for the confirmatory analysis of the co-primary endpoints by comparing the least square (LS) means estimates of an mixed model repeated measurement (MMRM) model (2-sided, significance level alpha=0.05) between treatment groups in the following order:

  1. IncobotulinumtoxinA 100 units versus (v) Placebo
  2. IncobotulinumtoxinA 75 units v Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.004
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.15 to 0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.031
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MP: Placebo, MP: IncobotulinumtoxinA (Xeomin) (75 Units)
Comments

A fixed sequence test procedure was used for the confirmatory analysis of the co-primary endpoints by comparing the least square means estimates of an MMRM model (2-sided, significance level alpha=0.05) between treatment groups in the following order:

  1. IncobotulinumtoxinA 100 units v Placebo
  2. IncobotulinumtoxinA 75 units v Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.542
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.08 to 0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.03
Estimation Comments [Not Specified]
2.Primary Outcome
Title MP: Participant's Global Impression of Change Scale (GICS) at Week 4
Hide Description The GICS was used to measure the impression of change due to treatment. The response option was a common 7-point Likert scale that ranged from -3 = very much worse to +3 = very much improved and was applicable for participant and caregiver. If the participant was not able to answer then carer's rating was to be recorded instead of participant's rating and the participant's rating was left blank.
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS is the subset of participants who were treated and had at least the baseline value of uSFR.
Arm/Group Title MP: Placebo MP: IncobotulinumtoxinA (Xeomin) (75 Units) MP: IncobotulinumtoxinA (Xeomin) (100 Units)
Hide Arm/Group Description:
Participants received one injection session of overall 2.0 mL placebo matched to the volume of incobotulinumtoxinA via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 75 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 100 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Overall Number of Participants Analyzed 36 74 74
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.67  (0.186) 1.02  (0.148) 1.25  (0.144)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection MP: Placebo, MP: IncobotulinumtoxinA (Xeomin) (100 Units)
Comments

A fixed sequence test procedure was used for the confirmatory analysis of the co-primary endpoints by comparing the least square means estimates of an MMRM model (2-sided, significance level alpha=0.05) between treatment groups in the following order:

  1. IncobotulinumtoxinA 100 units v Placebo
  2. IncobotulinumtoxinA 75 units v Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.002
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.22 to 0.94
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.183
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection MP: Placebo, MP: IncobotulinumtoxinA (Xeomin) (75 Units)
Comments

A fixed sequence test procedure was used for the confirmatory analysis of the co-primary endpoints by comparing the least square means estimates of an MMRM model (2-sided, significance level alpha=0.05) between treatment groups in the following order:

  1. IncobotulinumtoxinA 100 units v Placebo
  2. IncobotulinumtoxinA 75 units v Placebo
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.055
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
-0.01 to 0.71
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.181
Estimation Comments [Not Specified]
3.Secondary Outcome
Title MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 8 and 12
Hide Description uSFR was assessed by weighing of dental rolls soaked with saliva over 5 minutes and then procedure was repeated after 30 minutes and the average of the 2 results for flow rate was calculated.
Time Frame Baseline, Week 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis covers all participants from FAS who have at least one post-baseline uSFR assessment. The FAS is the subset of participants who were treated and had at least the baseline value of uSFR.
Arm/Group Title MP: Placebo MP: IncobotulinumtoxinA (Xeomin) (75 Units) MP: IncobotulinumtoxinA (Xeomin) (100 Units)
Hide Arm/Group Description:
Participants received one injection session of overall 2.0 mL placebo matched to the volume of incobotulinumtoxinA via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 75 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 100 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Overall Number of Participants Analyzed 36 73 73
Least Squares Mean (Standard Error)
Unit of Measure: g/min
Week 8 -0.02  (0.033) -0.08  (0.027) -0.13  (0.026)
Week 12 -0.03  (0.033) -0.1  (0.027) -0.12  (0.026)
4.Secondary Outcome
Title MP: Global Impression of Change Scale (GICS) at Week 1, 2, 8 and 12
Hide Description The GICS was used to measure the investigator's impression of change due to treatment. The response option was a common 7-point Likert scale that ranged from -3 = very much worse to +3 = very much improved and was applicable for participant and caregiver. If the participant was not able to answer then carer's rating was to be recorded instead of participant's rating and the participant's rating was left blank.
Time Frame Week 1, 2, 8, and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS is the subset of participants who were treated and had at least the baseline value of uSFR.
Arm/Group Title MP: Placebo MP: IncobotulinumtoxinA (Xeomin) (75 Units) MP: IncobotulinumtoxinA (Xeomin) (100 Units)
Hide Arm/Group Description:
Participants received one injection session of overall 2.0 mL placebo matched to the volume of incobotulinumtoxinA via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 75 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 100 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP.
Overall Number of Participants Analyzed 36 74 74
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 1 0.67  (0.17) 0.73  (0.138) 0.96  (0.133)
Week 2 0.83  (0.178) 0.91  (0.143) 1.11  (0.139)
Week 8 0.47  (0.192) 1.07  (0.151) 1.3  (0.148)
Week 12 0.56  (0.197) 0.98  (0.156) 1.21  (0.152)
Time Frame MP: From first injection up to first injection in EP (Week 16). EP: From first injection in EP (Week 16) up to end of study (Week 64).
Adverse Event Reporting Description The investigator asked the participant for adverse events systematically at each visit. Two participants received the wrong or no dose in single EP cycles due to procedural reasons and hence were not included in the safety analyses that cover the complete EP: IncobotulinumtoxinA (Xeomin) (75 Units) arm.
 
Arm/Group Title Placebo MP: IncobotulinumtoxinA (Xeomin) (75 Units) MP: IncobotulinumtoxinA (Xeomin) (100 Units) EP: IncobotulinumtoxinA (Xeomin) (75 Units) EP: IncobotulinumtoxinA (Xeomin) (100 Units)
Hide Arm/Group Description Participants received one injection session of overall 2.0 mL placebo matched to the volume of incobotulinumtoxinA via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP. Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 75 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP. Participants received one injection session of overall 2.0 mL incobotulinumtoxinA containing 100 units via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 in the MP. Participants received overall 2.0 mL incobotulinumtoxinA containing 75 units via bilateral intraglandular injection into the parotid and submandibular glands at each of the three injection sessions in the EP. Participants received overall 2.0 mL incobotulinumtoxinA containing 100 units via bilateral intraglandular injection into the parotid and submandibular glands at each of the three injection sessions in the EP.
All-Cause Mortality
Placebo MP: IncobotulinumtoxinA (Xeomin) (75 Units) MP: IncobotulinumtoxinA (Xeomin) (100 Units) EP: IncobotulinumtoxinA (Xeomin) (75 Units) EP: IncobotulinumtoxinA (Xeomin) (100 Units)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/36 (0.00%)      0/74 (0.00%)      0/74 (0.00%)      3/82 (3.66%)      2/89 (2.25%)    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo MP: IncobotulinumtoxinA (Xeomin) (75 Units) MP: IncobotulinumtoxinA (Xeomin) (100 Units) EP: IncobotulinumtoxinA (Xeomin) (75 Units) EP: IncobotulinumtoxinA (Xeomin) (100 Units)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/36 (8.33%)      6/74 (8.11%)      9/74 (12.16%)      15/82 (18.29%)      14/89 (15.73%)    
Blood and lymphatic system disorders           
Coagulopathy  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Cardiac disorders           
Atrial fibrillation  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Cardiac failure  1  1/36 (2.78%)  1 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Aortic valve stenosis  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Bradycardia  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Cardio-respiratory arrest  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Ear and labyrinth disorders           
Vertigo  1  1/36 (2.78%)  1 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 1/89 (1.12%)  1
Gastrointestinal disorders           
Diarrhoea  1  0/36 (0.00%)  0 0/74 (0.00%)  0 1/74 (1.35%)  1 0/82 (0.00%)  0 0/89 (0.00%)  0
Gastritis erosive  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Gastrointestinal obstruction  1  0/36 (0.00%)  0 0/74 (0.00%)  0 1/74 (1.35%)  1 0/82 (0.00%)  0 0/89 (0.00%)  0
Subileus  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Volvulus  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 2/82 (2.44%)  2 0/89 (0.00%)  0
Dysphagia  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  2
Faecal vomiting  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Gastric ulcer haemorrhage  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Gastrooesophageal reflux disease  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Giant cell epulis  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Megacolon  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Nausea  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Oesophageal food impaction  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
General disorders           
Chest pain  1  0/36 (0.00%)  0 0/74 (0.00%)  0 1/74 (1.35%)  1 0/82 (0.00%)  0 0/89 (0.00%)  0
General physical health deterioration  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Pain  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Pyrexia  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Hepatobiliary disorders           
Drug-induced liver injury  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Infections and infestations           
Pneumonia  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Pyuria  1  1/36 (2.78%)  1 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Urinary tract infection  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 2/82 (2.44%)  2 0/89 (0.00%)  0
Acute sinusitis  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Cellulitis  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Clostridium difficile infection  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Injury, poisoning and procedural complications           
Fall  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Femur fracture  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Lumbar vertebral fracture  1  0/36 (0.00%)  0 0/74 (0.00%)  0 1/74 (1.35%)  1 0/82 (0.00%)  0 0/89 (0.00%)  0
Rib fracture  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 1/89 (1.12%)  1
Chest injury  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Head injury  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Hip fracture  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  2 0/89 (0.00%)  0
Laceration  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Skin abrasion  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Spinal column injury  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Craniocerebral injury  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Investigations           
Angiogram  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Back pain  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Nervous system disorders           
Parkinson's disease  1  0/36 (0.00%)  0 1/74 (1.35%)  1 1/74 (1.35%)  1 6/82 (7.32%)  8 2/89 (2.25%)  2
Drop attacks  1  0/36 (0.00%)  0 0/74 (0.00%)  0 1/74 (1.35%)  1 0/82 (0.00%)  0 0/89 (0.00%)  0
Freezing phenomenon  1  0/36 (0.00%)  0 0/74 (0.00%)  0 1/74 (1.35%)  1 0/82 (0.00%)  0 0/89 (0.00%)  0
Akinesia  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Altered state of consciousness  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Cerebrovascular accident  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Dementia  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  2 0/89 (0.00%)  0
Generalised tonic-clonic seizure  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Movement disorder  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Orthostatic intolerance  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Presyncope  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Psychomotor hyperactivity  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Speech disorder  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Cardiac pacemaker insertion  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Product Issues           
Device occlusion  1  1/36 (2.78%)  1 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Psychiatric disorders           
Hallucination  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Delusion  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  2
Depression  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Dopamine dysregulation syndrome  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  2
Suicidal ideation  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Renal and urinary disorders           
Hydronephrosis  1  1/36 (2.78%)  1 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Urethral stenosis  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 2/89 (2.25%)  2
Extravasation of urine  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Respiratory, thoracic and mediastinal disorders           
Asthma  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Lower respiratory tract inflammation  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Pulmonary embolism  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Pneumonia aspiration  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 1/89 (1.12%)  1
Skin and subcutaneous tissue disorders           
Skin ulcer  1  0/36 (0.00%)  0 0/74 (0.00%)  0 1/74 (1.35%)  1 0/82 (0.00%)  0 1/89 (1.12%)  1
Surgical and medical procedures           
Coronary arterial stent insertion  1  0/36 (0.00%)  0 1/74 (1.35%)  1 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Medical device battery replacement  1  0/36 (0.00%)  0 0/74 (0.00%)  0 1/74 (1.35%)  1 0/82 (0.00%)  0 1/89 (1.12%)  1
Medical device change  1  0/36 (0.00%)  0 0/74 (0.00%)  0 1/74 (1.35%)  1 0/82 (0.00%)  0 0/89 (0.00%)  0
Rehabilitation therapy  1  0/36 (0.00%)  0 0/74 (0.00%)  0 1/74 (1.35%)  1 0/82 (0.00%)  0 0/89 (0.00%)  0
Angioplasty  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Appendicectomy  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Enterostomy  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Explorative laparotomy  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Laparotomy  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Nephrectomy  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Renal stone removal  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Ureter dilation procedure  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Ureteral stent insertion  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  1
Vascular disorders           
Orthostatic hypotension  1  1/36 (2.78%)  1 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 0/89 (0.00%)  0
Hypertensive crisis  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 1/82 (1.22%)  1 0/89 (0.00%)  0
Peripheral arterial occlusive disease  1  0/36 (0.00%)  0 0/74 (0.00%)  0 0/74 (0.00%)  0 0/82 (0.00%)  0 1/89 (1.12%)  2
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo MP: IncobotulinumtoxinA (Xeomin) (75 Units) MP: IncobotulinumtoxinA (Xeomin) (100 Units) EP: IncobotulinumtoxinA (Xeomin) (75 Units) EP: IncobotulinumtoxinA (Xeomin) (100 Units)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/36 (5.56%)      14/74 (18.92%)      10/74 (13.51%)      22/82 (26.83%)      22/89 (24.72%)    
Gastrointestinal disorders           
Dry mouth  1  0/36 (0.00%)  0 4/74 (5.41%)  5 3/74 (4.05%)  3 3/82 (3.66%)  4 10/89 (11.24%)  13
Infections and infestations           
Nasopharyngitis  1  1/36 (2.78%)  1 2/74 (2.70%)  2 2/74 (2.70%)  2 1/82 (1.22%)  1 6/89 (6.74%)  6
Upper respiratory tract infection  1  0/36 (0.00%)  0 2/74 (2.70%)  2 0/74 (0.00%)  0 5/82 (6.10%)  6 0/89 (0.00%)  0
Injury, poisoning and procedural complications           
Fall  1  0/36 (0.00%)  0 6/74 (8.11%)  8 2/74 (2.70%)  5 5/82 (6.10%)  9 4/89 (4.49%)  5
Contusion  1  0/36 (0.00%)  0 4/74 (5.41%)  5 0/74 (0.00%)  0 3/82 (3.66%)  3 1/89 (1.12%)  1
Surgical and medical procedures           
Tooth extraction  1  0/36 (0.00%)  0 0/74 (0.00%)  0 4/74 (5.41%)  4 3/82 (3.66%)  4 4/89 (4.49%)  5
Vascular disorders           
Hypertension  1  1/36 (2.78%)  1 2/74 (2.70%)  2 3/74 (4.05%)  3 5/82 (6.10%)  5 2/89 (2.25%)  2
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Publication of study information usually requires agreement with the sponsor. In case of justified doubts by the sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.
Results Point of Contact
Name/Title: Public Disclosure Manager
Organization: Merz Pharmaceuticals GmbH
Phone: +49 69 1503 1
Responsible Party: Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier: NCT02091739     History of Changes
Other Study ID Numbers: MRZ60201_3090_1
2012-005539-10 ( EudraCT Number )
First Submitted: March 18, 2014
First Posted: March 19, 2014
Results First Submitted: January 15, 2018
Results First Posted: February 15, 2018
Last Update Posted: March 27, 2018