Back to resultsClinical 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)
Primary Purpose
Chronic Troublesome Sialorrhea, Parkinson's Disease, Post-stroke
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
IncobotulinumtoxinA (100 Units)
IncobotulinumtoxinA (75 Units)
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Troublesome Sialorrhea
Eligibility Criteria
Inclusion Criteria:
- Documented diagnosis of the basic neurological condition associated with sialorrhea (as above, (i), (ii) or (iii); with onset at least 6 months before screening).
Chronic troublesome sialorrhea related to parkinsonism or stroke or traumatic brain injury (for at least 3 months) at screening, defined as the presence of all of the following, at screening and at baseline and for at least the 3 months before screening (where retrospective response to questionnaires is impossible, a statement of equivalent severity will suffice):
- A Drooling Severity and Frequency Scale [DSFS] sum score of at least 6 points and
- A score of at least 2 points for each item of the DSFS and
- A score of at least 3 points on the modified Radboud Oral Motor Inventory for Parkinson's Disease [mROMP], Section 'III Drooling', Item A).
- A score of at most 2 points on the mROMP Section 'II Swallowing Symptoms' Item A) and a score of at most 3 points on Item C), at screening and at baseline.
Exclusion Criteria:
- Non-neurological secondary causes of sialorrhea.
- Unstable concomitant medication influencing sialorrhea (such as anticholinergics for the treatment of parkinsonism; dosages of these medications must have been stable for at least 4 weeks before study entry, i.e. screening, and must be planned to remain stable during the course of the study.
- Recent (i.e., four weeks) drug treatment for sialorrhea.
- History of recurrent aspiration pneumonia.
- Extremely poor dental/oral condition as assessed by a qualified dentist.
- Recent (i.e., one year for sialorrhea, 14 weeks for other indications) treatment with - or known hypersensitivity to - Botulinum toxin, or known hypersensitivity to any ingredient of the study preparation.
- Recent (i.e., four weeks) changes in anti-parkinsonian medication.
- Previous or planned surgery or irradiation to control sialorrhea.
Sites / Locations
- Merz investigational site #049172
- Merz Investigational Site #049335
- Merz Investigational Site #049337
- Merz Investigational Site #049072
- Merz Investigational Site #049148
- Merz Investigational Site #049300
- Merz Investigational Site #049303
- Merz investigational site #049348
- Merz Investigational Site #049143
- Merz Investigational Site #049333
- Merz Investigational Site #049302
- Merz investigational site #048068
- Merz Investigational Site #048088
- Merz Investigational Site #048029
- Merz investigational site #048074
- Merz investigational site #048078
- Merz investigational site #048076
- Merz investigational site #048077
- Merz investigational Site #048067
- Merz investigational site #048059
- Merz investigational site #048031
- Merz Investigational Site #048087
- Merz Investigational Site #048022
- Merz investigational site #048070
- Merz investigational site #048085
- Merz investigational site #048072
- Merz Investigational Site #048075
- Merz Investigational Site #048086
- Merz investigational site #048065
- Merz investigational site #048056
- Merz investigational site #048064
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
IncobotulinumtoxinA (Xeomin) (100 Units)
IncobotulinumtoxinA (Xeomin) (75 Units)
Placebo
Arm Description
Main period (1 treatment cycle): Subjects to receive 100 Units. Extension period (3 treatment cycles): Subjects to receive 100 Units per treatment cycle. Mode of administration: Four injections per treatment cycle (parotid and submandibular glands, bilateral)
Main period (1 treatment cycle): Subjects to receive 75 Units. Extension period (3 treatment cycles): Subjects to receive 75 Units per treatment cycle. Mode of administration: Four injections per treatment cycle (parotid and submandibular glands, bilateral)
Main period (1 treatment cycle): Subjects to receive placebo injection. Extension period (3 treatment cycles): Subjects will be randomized to receive either 75 or 100 Units IncobotulinumtoxinA per treatment cycle. Mode of administration: Four injections per treatment cycle (parotid and submandibular glands, bilateral)
Outcomes
Primary Outcome Measures
MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 4
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.
MP: Participant's Global Impression of Change Scale (GICS) at Week 4
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.
Secondary Outcome Measures
MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 8 and 12
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.
MP: Global Impression of Change Scale (GICS) at Week 1, 2, 8 and 12
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.
Full Information
NCT ID
NCT02091739
First Posted
March 18, 2014
Last Updated
February 27, 2018
Sponsor
Merz Pharmaceuticals GmbH
1. Study Identification
Unique Protocol Identification Number
NCT02091739
Brief Title
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
Acronym
SIAXI
Official Title
Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group Multicenter Study, With an Extension Period of Dose-blinded Active Treatment, to Investigate the Efficacy and Safety of Two Dose Levels of NT 201 in Treating Chronic Troublesome Sialorrhea in Various Neurological Conditions
Study Type
Interventional
2. Study Status
Record Verification Date
January 2018
Overall Recruitment Status
Completed
Study Start Date
April 2014 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
November 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merz Pharmaceuticals GmbH
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The objective of this study is to investigate the efficacy and safety of two different dose levels of NT 201 (75 U or 100 U per cycle), compared with placebo, in reducing the salivary flow rate, and the severity and frequency of chronic troublesome sialorrhea that occurs as a result of various neurological conditions in adult subjects.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Troublesome Sialorrhea, Parkinson's Disease, Post-stroke, Traumatic Brain Injury
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
184 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IncobotulinumtoxinA (Xeomin) (100 Units)
Arm Type
Experimental
Arm Description
Main period (1 treatment cycle): Subjects to receive 100 Units.
Extension period (3 treatment cycles): Subjects to receive 100 Units per treatment cycle.
Mode of administration: Four injections per treatment cycle (parotid and submandibular glands, bilateral)
Arm Title
IncobotulinumtoxinA (Xeomin) (75 Units)
Arm Type
Experimental
Arm Description
Main period (1 treatment cycle): Subjects to receive 75 Units.
Extension period (3 treatment cycles): Subjects to receive 75 Units per treatment cycle.
Mode of administration: Four injections per treatment cycle (parotid and submandibular glands, bilateral)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Main period (1 treatment cycle): Subjects to receive placebo injection.
Extension period (3 treatment cycles): Subjects will be randomized to receive either 75 or 100 Units IncobotulinumtoxinA per treatment cycle.
Mode of administration: Four injections per treatment cycle (parotid and submandibular glands, bilateral)
Intervention Type
Drug
Intervention Name(s)
IncobotulinumtoxinA (100 Units)
Other Intervention Name(s)
Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Intervention Description
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
Intervention Type
Drug
Intervention Name(s)
IncobotulinumtoxinA (75 Units)
Other Intervention Name(s)
Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Intervention Description
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
Primary Outcome Measure Information:
Title
MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 4
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
Title
MP: Participant's Global Impression of Change Scale (GICS) at Week 4
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
Secondary Outcome Measure Information:
Title
MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 8 and 12
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
Title
MP: Global Impression of Change Scale (GICS) at Week 1, 2, 8 and 12
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Documented diagnosis of the basic neurological condition associated with sialorrhea (as above, (i), (ii) or (iii); with onset at least 6 months before screening).
Chronic troublesome sialorrhea related to parkinsonism or stroke or traumatic brain injury (for at least 3 months) at screening, defined as the presence of all of the following, at screening and at baseline and for at least the 3 months before screening (where retrospective response to questionnaires is impossible, a statement of equivalent severity will suffice):
A Drooling Severity and Frequency Scale [DSFS] sum score of at least 6 points and
A score of at least 2 points for each item of the DSFS and
A score of at least 3 points on the modified Radboud Oral Motor Inventory for Parkinson's Disease [mROMP], Section 'III Drooling', Item A).
A score of at most 2 points on the mROMP Section 'II Swallowing Symptoms' Item A) and a score of at most 3 points on Item C), at screening and at baseline.
Exclusion Criteria:
Non-neurological secondary causes of sialorrhea.
Unstable concomitant medication influencing sialorrhea (such as anticholinergics for the treatment of parkinsonism; dosages of these medications must have been stable for at least 4 weeks before study entry, i.e. screening, and must be planned to remain stable during the course of the study.
Recent (i.e., four weeks) drug treatment for sialorrhea.
History of recurrent aspiration pneumonia.
Extremely poor dental/oral condition as assessed by a qualified dentist.
Recent (i.e., one year for sialorrhea, 14 weeks for other indications) treatment with - or known hypersensitivity to - Botulinum toxin, or known hypersensitivity to any ingredient of the study preparation.
Recent (i.e., four weeks) changes in anti-parkinsonian medication.
Previous or planned surgery or irradiation to control sialorrhea.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Merz Medical Expert
Organizational Affiliation
Merz Pharmaceuticals GmbH
Official's Role
Study Director
Facility Information:
Facility Name
Merz investigational site #049172
City
Bonn
ZIP/Postal Code
53105
Country
Germany
Facility Name
Merz Investigational Site #049335
City
Gera
ZIP/Postal Code
07551
Country
Germany
Facility Name
Merz Investigational Site #049337
City
Haag i.OB
ZIP/Postal Code
83527
Country
Germany
Facility Name
Merz Investigational Site #049072
City
Munich
ZIP/Postal Code
80804
Country
Germany
Facility Name
Merz Investigational Site #049148
City
Munich
ZIP/Postal Code
81675
Country
Germany
Facility Name
Merz Investigational Site #049300
City
Nümbrecht
ZIP/Postal Code
51588
Country
Germany
Facility Name
Merz Investigational Site #049303
City
Regensburg
ZIP/Postal Code
93053
Country
Germany
Facility Name
Merz investigational site #049348
City
Stadtroda
ZIP/Postal Code
07646
Country
Germany
Facility Name
Merz Investigational Site #049143
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Facility Name
Merz Investigational Site #049333
City
Wolfach
ZIP/Postal Code
77709
Country
Germany
Facility Name
Merz Investigational Site #049302
City
Wuerzburg
ZIP/Postal Code
97080
Country
Germany
Facility Name
Merz investigational site #048068
City
Bydgoszcz
ZIP/Postal Code
85-015
Country
Poland
Facility Name
Merz Investigational Site #048088
City
Bydgoszcz
ZIP/Postal Code
85-080
Country
Poland
Facility Name
Merz Investigational Site #048029
City
Gdansk
ZIP/Postal Code
80-254
Country
Poland
Facility Name
Merz investigational site #048074
City
Gdansk
ZIP/Postal Code
80-546
Country
Poland
Facility Name
Merz investigational site #048078
City
Jaworzno
ZIP/Postal Code
43-600
Country
Poland
Facility Name
Merz investigational site #048076
City
Katowice
ZIP/Postal Code
40-097
Country
Poland
Facility Name
Merz investigational site #048077
City
Katowice
ZIP/Postal Code
40-097
Country
Poland
Facility Name
Merz investigational Site #048067
City
Kielce
ZIP/Postal Code
25-103
Country
Poland
Facility Name
Merz investigational site #048059
City
Krakow
ZIP/Postal Code
30-539
Country
Poland
Facility Name
Merz investigational site #048031
City
Krakow
ZIP/Postal Code
31-505
Country
Poland
Facility Name
Merz Investigational Site #048087
City
Krakow
ZIP/Postal Code
31-530
Country
Poland
Facility Name
Merz Investigational Site #048022
City
Lodz
ZIP/Postal Code
90-130
Country
Poland
Facility Name
Merz investigational site #048070
City
Lublin
ZIP/Postal Code
20-718
Country
Poland
Facility Name
Merz investigational site #048085
City
Lublin
ZIP/Postal Code
30-539
Country
Poland
Facility Name
Merz investigational site #048072
City
Lubon
ZIP/Postal Code
62-030
Country
Poland
Facility Name
Merz Investigational Site #048075
City
Sandomierz
ZIP/Postal Code
27-600
Country
Poland
Facility Name
Merz Investigational Site #048086
City
Torun
ZIP/Postal Code
87-100
Country
Poland
Facility Name
Merz investigational site #048065
City
Warszawa
ZIP/Postal Code
00-453
Country
Poland
Facility Name
Merz investigational site #048056
City
Warszawa
ZIP/Postal Code
02-097
Country
Poland
Facility Name
Merz investigational site #048064
City
Warszawa
ZIP/Postal Code
03-242
Country
Poland
12. IPD Sharing Statement
Citations:
PubMed Identifier
31794936
Citation
Jost WH, Friedman A, Michel O, Oehlwein C, Slawek J, Bogucki A, Ochudlo S, Banach M, Pagan F, Flatau-Baque B, Dorsch U, Csikos J, Blitzer A. Long-term incobotulinumtoxinA treatment for chronic sialorrhea: Efficacy and safety over 64 weeks. Parkinsonism Relat Disord. 2020 Jan;70:23-30. doi: 10.1016/j.parkreldis.2019.11.024. Epub 2019 Nov 26.
Results Reference
derived
PubMed Identifier
30918101
Citation
Jost WH, Friedman A, Michel O, Oehlwein C, Slawek J, Bogucki A, Ochudlo S, Banach M, Pagan F, Flatau-Baque B, Csikos J, Cairney CJ, Blitzer A. SIAXI: Placebo-controlled, randomized, double-blind study of incobotulinumtoxinA for sialorrhea. Neurology. 2019 Apr 23;92(17):e1982-e1991. doi: 10.1212/WNL.0000000000007368. Epub 2019 Mar 27.
Results Reference
derived
Learn more about this trial
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
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