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Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability (SIPEXI)

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ClinicalTrials.gov Identifier: NCT02270736
Recruitment Status : Completed
First Posted : October 21, 2014
Results First Posted : January 20, 2021
Last Update Posted : August 10, 2021
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
Cerebral Palsy
Stroke
Traumatic Brain Injury
Intellectual Disability
Interventions Drug: NT 201 Placebo
Drug: NT 201
Enrollment 256
Recruitment Details The study was conducted at 28 investigational sites in Georgia, Hungary, Poland, Russia, Serbia, and Ukraine.
Pre-assignment Details A total of 281 participants were screened, out of which 256 participants were enrolled/randomized into the study. Of these 256 participants, 255 participants received the study treatment. A total of 247 participants who completed the Main Period (MP) entered the Open-label Extension Period (OLEX) of the study.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) OLEX: NT 201 (Age 6 to 17 Years) OLEX: NT 201 (Age 2 to 5 Years)
Hide Arm/Group Description Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm. Participants received NT 201 (up to 2.5 Units per kilogram [U/kg] body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm consisted of participants who participated in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)". Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).
Period Title: Main Period (MP) (up to 16 Weeks)
Started 72 148 36 0 0
Treated 72 148 35 0 0
Completed 70 146 34 0 0
Not Completed 2 2 2 0 0
Reason Not Completed
Adverse Event             0             1             0             0             0
Withdrawal by Subject             2             0             1             0             0
Lost to Follow-up             0             1             0             0             0
Randomized, not Treated             0             0             1             0             0
Period Title: OLEX Period (up to 48 Weeks)
Started 0 0 0 214 [1] 33 [2]
Completed 0 0 0 189 33
Not Completed 0 0 0 25 0
Reason Not Completed
Physician Decision             0             0             0             1             0
Lack of Efficacy             0             0             0             2             0
Adverse Event             0             0             0             4             0
Withdrawal by Subject             0             0             0             16             0
Lost to Follow-up             0             0             0             2             0
[1]
2 participants from MP did not enter OLEX due to withdrawal of consent.
[2]
1 participant from MP did not enter OLEX due to adverse event.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) Total
Hide Arm/Group Description Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm. Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Total of all reporting groups
Overall Number of Baseline Participants 72 148 35 255
Hide Baseline Analysis Population Description
The safety evaluable set (SES) (MP) is the subset of all participants who received study medication (NT 201 or placebo) during the MP of the study.
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants 148 participants 35 participants 255 participants
In utero
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Preterm newborn infants (gestational age < 37 wks)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Newborns (0-27 days)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Infants and toddlers (28 days-23 months)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Children (2-11 years)
48
  66.7%
96
  64.9%
35
 100.0%
179
  70.2%
Adolescents (12-17 years)
24
  33.3%
52
  35.1%
0
   0.0%
76
  29.8%
Adults (18-64 years)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
From 65-84 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
85 years and over
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants 148 participants 35 participants 255 participants
Female
27
  37.5%
55
  37.2%
13
  37.1%
95
  37.3%
Male
45
  62.5%
93
  62.8%
22
  62.9%
160
  62.7%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 72 participants 148 participants 35 participants 255 participants
White
72
 100.0%
148
 100.0%
35
 100.0%
255
 100.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeter (cm)
Number Analyzed 72 participants 148 participants 35 participants 255 participants
135.3  (16.92) 132.8  (17.15) 101.1  (8.09) 129.1  (19.64)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 72 participants 148 participants 35 participants 255 participants
30.8  (11.67) 28.8  (11.48) 15.7  (3.00) 27.6  (11.78)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 72 participants 148 participants 35 participants 255 participants
16.4  (3.65) 15.8  (3.25) 15.3  (1.85) 15.9  (3.23)
1.Primary Outcome
Title Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4
Hide Description This endpoint was planned to be analyzed in double-blind, MP, 6 to 17 years participants only. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and the procedure was repeated after 30 minutes. Salivary flow rate was equal to weight increase of swabs/time of collection. The average of the 2 results for flow rate was calculated. The reduction of measured weight over the study relates to improvement of sialorrhea.
Time Frame Baseline and Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The full analysis set (FAS) is identical to the subset of participants in the SES (MP) where subset of all participants received study medication (NT 201 or placebo) during the MP of the study.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years)
Hide Arm/Group Description:
Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
Participants received NT 201 (up to 2.5 Units per kilogram [U/kg] body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Overall Number of Participants Analyzed 72 148
Least Squares Mean (Standard Error)
Unit of Measure: gram per minute (g/min)
-0.07  (0.015) -0.14  (0.012)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-blind MP: Placebo (Age 6 to 17 Years), Double-blind, MP: NT 201 (Age 6 to 17 Years)
Comments Least square mean (LS-Mean) is from a mixed model repeated measurement (MMRM) analysis with treatment group, pooled investigation sites, and age groups as fixed factors, visit*treatment as interaction term, visit as repeated factor, and baseline uSFR score as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.0012
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean (LS-mean) difference
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-0.1 to -0.03
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.019
Estimation Comments [Not Specified]
2.Primary Outcome
Title Global Impression of Change Scale (GICS) at Week 4 Assessed by the Carer/Parent(s)
Hide Description This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. The GICS was used to measure the carer's/parent's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).
Time Frame Week 4
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS is identical to the subset of participants in the SES (MP) where subset of all participants received study medication (NT 201 or placebo) during the MP of the study.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years)
Hide Arm/Group Description:
Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Overall Number of Participants Analyzed 72 148
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
0.63  (0.104) 0.91  (0.075)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-blind MP: Placebo (Age 6 to 17 Years), Double-blind, MP: NT 201 (Age 6 to 17 Years)
Comments LS-Mean is from a MMRM analysis model with treatment group, pooled investigation sites, and age groups as fixed factors, visit*treatment as interaction term, visit as repeated factor, and baseline Modified Teacher Drooling Scale (mTDS) score as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.032
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean (LS-mean) difference
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.02 to 0.53
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.127
Estimation Comments [Not Specified]
3.Primary Outcome
Title Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle
Hide Description [Not Specified]
Time Frame Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
SES: subset of all participants who received study medication (NT 201 or placebo) during MP or (NT 201) during OLEX of study. "n" is number of participants evaluable for this measure at a given time period and who were included in the assessment.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) OLEX: NT 201 (Age 6 to 17 Years) OLEX: NT 201 (Age 2 to 5 Years)
Hide Arm/Group Description:
Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm consisted of participants who participated in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)".
Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).
Overall Number of Participants Analyzed 72 148 35 214 33
Measure Type: Count of Participants
Unit of Measure: Participants
Overall Number Analyzed 72 participants 148 participants 35 participants 214 participants 33 participants
11
  15.3%
27
  18.2%
5
  14.3%
92
  43.0%
15
  45.5%
First injection cycle (MP) Number Analyzed 72 participants 148 participants 35 participants 0 participants 0 participants
11
  15.3%
27
  18.2%
5
  14.3%
Second injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 214 participants 33 participants
44
  20.6%
7
  21.2%
Third injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 205 participants 33 participants
35
  17.1%
5
  15.2%
Fourth injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 193 participants 33 participants
40
  20.7%
11
  33.3%
4.Secondary Outcome
Title Change From Baseline in uSFR at Weeks 8 and 12
Hide Description This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and then procedure was repeated after 30 minutes. Salivary flow rate was equal to weight increase of swabs/time of collection. The average of the 2 results for flow rate was calculated. The reduction of measured weight over the study relates to improvement of sialorrhea.
Time Frame Baseline and Weeks 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS is identical to the subset of participants in the SES (MP) where subset of all participants received study medication (NT 201 or placebo) during the MP of the study.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years)
Hide Arm/Group Description:
Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Overall Number of Participants Analyzed 72 148
Least Squares Mean (Standard Error)
Unit of Measure: g/min
Change at Week 8 -0.07  (0.015) -0.16  (0.012)
Change at Week 12 -0.06  (0.016) -0.16  (0.013)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-blind MP: Placebo (Age 6 to 17 Years), Double-blind, MP: NT 201 (Age 6 to 17 Years)
Comments Statistical analysis at Week 8: LS-Mean is from a MMRM analysis with treatment group, pooled investigation sites, and age groups as fixed factors, visit*treatment as interaction term, visit as repeated factor, and baseline uSFR score as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean (LS-mean) difference
Estimated Value -0.09
Confidence Interval (2-Sided) 95%
-0.12 to -0.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.019
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-blind MP: Placebo (Age 6 to 17 Years), Double-blind, MP: NT 201 (Age 6 to 17 Years)
Comments Statistical analysis at Week 12: LS-Mean is from a MMRM analysis with treatment group, pooled investigation sites, and age groups as fixed factors, visit*treatment as interaction term, visit as repeated factor, and baseline uSFR score as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean (LS-mean) difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-0.14 to -0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.021
Estimation Comments [Not Specified]
5.Secondary Outcome
Title GICS at Weeks 8 and 12
Hide Description This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. The GICS was used to measure the carer's/parent's impression of change due to treatment. The response option was a common 7-point Likert scale with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).
Time Frame Weeks 8 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS is identical to the subset of participants in the SES (MP) where subset of all participants received study medication (NT 201 or placebo) during the MP of the study.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years)
Hide Arm/Group Description:
Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Overall Number of Participants Analyzed 72 148
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
Week 8 0.54  (0.096) 0.94  (0.068)
Week 12 0.47  (0.111) 0.87  (0.073)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Double-blind MP: Placebo (Age 6 to 17 Years), Double-blind, MP: NT 201 (Age 6 to 17 Years)
Comments Statistical analysis at Week 8: LS-Mean is from a MMRM analysis model with treatment group, pooled investigation sites, and age groups as fixed factors, visit*treatment as interaction term, visit as repeated factor, and baseline mTDS score as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0008
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean (LS-mean) difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
0.17 to 0.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.116
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Double-blind MP: Placebo (Age 6 to 17 Years), Double-blind, MP: NT 201 (Age 6 to 17 Years)
Comments Statistical analysis at Week 12: LS-Mean is from a MMRM analysis model with treatment group, pooled investigation sites, and age groups as fixed factors, visit*treatment as interaction term, visit as repeated factor, and baseline mTDS score as covariate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.0026
Comments [Not Specified]
Method MMRM
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean (LS-mean) difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
0.14 to 0.66
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.132
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle
Hide Description [Not Specified]
Time Frame Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
SES: subset of all participants who received study medication (NT 201 or placebo) during MP or (NT 201) during OLEX of study. "n" is number of participants evaluable for this measure at a given time period and who were included in the assessment.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) OLEX: NT 201 (Age 6 to 17 Years) OLEX: NT 201 (Age 2 to 5 Years)
Hide Arm/Group Description:
Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm consisted of participants who participated in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)".
Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).
Overall Number of Participants Analyzed 72 148 35 214 33
Measure Type: Count of Participants
Unit of Measure: Participants
Overall Number Analyzed 72 participants 148 participants 35 participants 214 participants 33 participants
0
   0.0%
1
   0.7%
0
   0.0%
4
   1.9%
0
   0.0%
First injection cycle (MP) Number Analyzed 72 participants 148 participants 35 participants 0 participants 0 participants
0
   0.0%
1
   0.7%
0
   0.0%
Second injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 214 participants 33 participants
3
   1.4%
0
   0.0%
Third injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 205 participants 33 participants
1
   0.5%
0
   0.0%
Fourth injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 193 participants 33 participants
0
   0.0%
0
   0.0%
7.Secondary Outcome
Title Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle
Hide Description [Not Specified]
Time Frame Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
SES: subset of all participants who received study medication (NT 201 or placebo) during MP or (NT 201) during OLEX of study. "n" is number of participants evaluable for this measure at a given time period and who were included in the assessment.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) OLEX: NT 201 (Age 6 to 17 Years) OLEX: NT 201 (Age 2 to 5 Years)
Hide Arm/Group Description:
Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm consisted of participants who participated in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)".
Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).
Overall Number of Participants Analyzed 72 148 35 214 33
Measure Type: Count of Participants
Unit of Measure: Participants
Overall Number Analyzed 72 participants 148 participants 35 participants 214 participants 33 participants
1
   1.4%
0
   0.0%
1
   2.9%
8
   3.7%
0
   0.0%
First injection cycle (MP) Number Analyzed 72 participants 148 participants 35 participants 0 participants 0 participants
1
   1.4%
0
   0.0%
1
   2.9%
Second injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 214 participants 33 participants
3
   1.4%
0
   0.0%
Third injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 205 participants 33 participants
5
   2.4%
0
   0.0%
Fourth injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 193 participants 33 participants
0
   0.0%
0
   0.0%
8.Secondary Outcome
Title Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle
Hide Description [Not Specified]
Time Frame Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
SES: subset of all participants who received study medication (NT 201 or placebo) during MP or (NT 201) during OLEX of study. "n" is number of participants evaluable for this measure at a given time period and who were included in the assessment.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) OLEX: NT 201 (Age 6 to 17 Years) OLEX: NT 201 (Age 2 to 5 Years)
Hide Arm/Group Description:
Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm consisted of participants who participated in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)".
Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).
Overall Number of Participants Analyzed 72 148 35 214 33
Measure Type: Count of Participants
Unit of Measure: Participants
Overall Number Analyzed 72 participants 148 participants 35 participants 214 participants 33 participants
0
   0.0%
2
   1.4%
1
   2.9%
10
   4.7%
0
   0.0%
First injection cycle (MP) Number Analyzed 72 participants 148 participants 35 participants 0 participants 0 participants
0
   0.0%
2
   1.4%
1
   2.9%
Second injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 214 participants 33 participants
5
   2.3%
0
   0.0%
Third injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 205 participants 33 participants
5
   2.4%
0
   0.0%
Fourth injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 193 participants 33 participants
1
   0.5%
0
   0.0%
9.Secondary Outcome
Title Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle
Hide Description [Not Specified]
Time Frame Baseline up to Week 64
Hide Outcome Measure Data
Hide Analysis Population Description
SES: subset of all participants who received study medication (NT 201 or placebo) during MP or (NT 201) during OLEX of study. "n" is number of participants evaluable for this measure at a given time period and who were included in the assessment.
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) OLEX: NT 201 (Age 6 to 17 Years) OLEX: NT 201 (Age 2 to 5 Years)
Hide Arm/Group Description:
Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.
Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm consisted of participants who participated in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)".
Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).
Overall Number of Participants Analyzed 72 148 35 214 33
Measure Type: Count of Participants
Unit of Measure: Participants
Overall Number Analyzed 72 participants 148 participants 35 participants 214 participants 33 participants
1
   1.4%
1
   0.7%
1
   2.9%
4
   1.9%
0
   0.0%
First injection cycle (MP) Number Analyzed 72 participants 148 participants 35 participants 0 participants 0 participants
1
   1.4%
1
   0.7%
1
   2.9%
Second injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 214 participants 33 participants
2
   0.9%
0
   0.0%
Third injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 205 participants 33 participants
2
   1.0%
0
   0.0%
Fourth injection cycle (OLEX) Number Analyzed 0 participants 0 participants 0 participants 193 participants 33 participants
0
   0.0%
0
   0.0%
Time Frame Baseline up to Week 64
Adverse Event Reporting Description The investigator asked the participant for adverse events (AEs) systematically at each visit.
 
Arm/Group Title Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) OLEX: NT 201 (Age 6 to 17 Years) OLEX: NT 201 (Age 2 to 5 Years)
Hide Arm/Group Description Participants received placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes were matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm. Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Participants received NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm consisted of participants who participated in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)". Participants received NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).
All-Cause Mortality
Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) OLEX: NT 201 (Age 6 to 17 Years) OLEX: NT 201 (Age 2 to 5 Years)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/72 (0.00%)      0/148 (0.00%)      0/35 (0.00%)      0/214 (0.00%)      0/33 (0.00%)    
Hide Serious Adverse Events
Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) OLEX: NT 201 (Age 6 to 17 Years) OLEX: NT 201 (Age 2 to 5 Years)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/72 (1.39%)      0/148 (0.00%)      1/35 (2.86%)      8/214 (3.74%)      0/33 (0.00%)    
Blood and lymphatic system disorders           
Anaemia  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  1 0/33 (0.00%)  0
Gastrointestinal disorders           
Functional gastrointestinal disorder  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 2/214 (0.93%)  2 0/33 (0.00%)  0
Gastrointestinal haemorrhage  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  1 0/33 (0.00%)  0
Haematemesis  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  1 0/33 (0.00%)  0
Infections and infestations           
Staphylococcal bacteraemia  1  0/72 (0.00%)  0 0/148 (0.00%)  0 1/35 (2.86%)  1 0/214 (0.00%)  0 0/33 (0.00%)  0
Gastroenteritis rotavirus  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  1 0/33 (0.00%)  0
Influenza  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  2 0/33 (0.00%)  0
Pneumonia  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  1 0/33 (0.00%)  0
Pneumonia bacterial  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  2 0/33 (0.00%)  0
Respiratory tract infection  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  1 0/33 (0.00%)  0
Injury, poisoning and procedural complications           
Foreign body in gastrointestinal tract  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  1 0/33 (0.00%)  0
Joint dislocation  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  1 0/33 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Limb deformity  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  1 0/33 (0.00%)  0
Nervous system disorders           
Generalised tonic-clonic seizure  1  0/72 (0.00%)  0 0/148 (0.00%)  0 1/35 (2.86%)  1 0/214 (0.00%)  0 0/33 (0.00%)  0
Epilepsy  1  1/72 (1.39%)  1 0/148 (0.00%)  0 0/35 (0.00%)  0 0/214 (0.00%)  0 0/33 (0.00%)  0
Surgical and medical procedures           
Gastric operation  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  1 0/33 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Double-blind MP: Placebo (Age 6 to 17 Years) Double-blind, MP: NT 201 (Age 6 to 17 Years) Open-label, MP: NT 201 (Age 2 to 5 Years) OLEX: NT 201 (Age 6 to 17 Years) OLEX: NT 201 (Age 2 to 5 Years)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/72 (4.17%)      3/148 (2.03%)      2/35 (5.71%)      34/214 (15.89%)      12/33 (36.36%)    
Infections and infestations           
Nasopharyngitis  1  3/72 (4.17%)  3 3/148 (2.03%)  3 2/35 (5.71%)  3 13/214 (6.07%)  16 1/33 (3.03%)  1
Pharyngitis  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 12/214 (5.61%)  13 3/33 (9.09%)  3
Respiratory tract infection  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 6/214 (2.80%)  6 3/33 (9.09%)  4
Viral infection  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 4/214 (1.87%)  7 2/33 (6.06%)  3
Respiratory tract infection viral  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 1/214 (0.47%)  2 4/33 (12.12%)  5
Rhinitis  1  0/72 (0.00%)  0 0/148 (0.00%)  0 0/35 (0.00%)  0 2/214 (0.93%)  2 3/33 (9.09%)  4
1
Term from vocabulary, MedDRA 22.0
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
Layout table for Results Point of Contact information
Name/Title: Public Disclosure Manager
Organization: Merz Pharmaceuticals GmbH
Phone: +49 69 1503 1
EMail: clinicaltrials@merz.com
Layout table for additonal information
Responsible Party: Merz Pharmaceuticals GmbH
ClinicalTrials.gov Identifier: NCT02270736    
Other Study ID Numbers: MRZ60201_3091_1
2013-004532-30 ( EudraCT Number )
First Submitted: October 17, 2014
First Posted: October 21, 2014
Results First Submitted: December 23, 2020
Results First Posted: January 20, 2021
Last Update Posted: August 10, 2021