Chronic Troublesome SialorrheaPhase 3SIAXINCT02091739

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

A Phase 3 study testing IncobotulinumtoxinA (100 Units) and IncobotulinumtoxinA (75 Units) in people with Chronic Troublesome Sialorrhea and Parkinson's Disease, run by Merz Pharmaceuticals GmbH at 31 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Chronic Troublesome Sialorrhea, Parkinson's Disease, Post-stroke
What is being tested?: IncobotulinumtoxinA (100 Units) and IncobotulinumtoxinA (75 Units)
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 184 participants
Where: 31 sitesin 2 countries
Study dates: Apr 2014to Nov 2016
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

31 sites in 2 countries.

Country

City, postcode or hospital

31 sites in 2 countries

Poland20 sites

Merz investigational site #048068
Bydgoszcz, 85-015
Merz Investigational Site #048088
Bydgoszcz, 85-080
Merz Investigational Site #048029
Gdansk, 80-254
Merz investigational site #048074
Gdansk, 80-546
Merz investigational site #048078
Jaworzno, 43-600
Merz investigational site #048076
Katowice, 40-097
Merz investigational site #048077
Katowice, 40-097
Merz investigational Site #048067
Kielce, 25-103
Merz investigational site #048059
Krakow, 30-539
Merz investigational site #048031
Krakow, 31-505
Merz Investigational Site #048087
Krakow, 31-530
Merz Investigational Site #048022
Lodz, 90-130
Merz investigational site #048070
Lublin, 20-718
Merz investigational site #048085
Lublin, 30-539
Merz investigational site #048072
Luboń, 62-030
Merz Investigational Site #048075
Sandomierz, 27-600
Merz Investigational Site #048086
Torun, 87-100
Merz investigational site #048065
Warsaw, 00-453
Merz investigational site #048056
Warsaw, 02-097
Merz investigational site #048064
Warsaw, 03-242

Other trials in Poland

Germany11 sites

Merz investigational site #049172
Bonn, 53105
Merz Investigational Site #049335
Gera, 07551
Merz Investigational Site #049337
Haag i.OB, 83527
Merz Investigational Site #049072
Munich, 80804
Merz Investigational Site #049148
Munich, 81675
Merz Investigational Site #049300
Nümbrecht, 51588
Merz Investigational Site #049303
Regensburg, 93053
Merz investigational site #049348
Stadtroda, 07646
Merz Investigational Site #049143
Ulm, 89081
Merz Investigational Site #049333
Wolfach, 77709
Merz Investigational Site #049302
Würzburg, 97080

Other trials in Germany

About this study

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

Conditions: Chronic Troublesome Sialorrhea, Parkinson's Disease, Post-stroke, Traumatic Brain Injury
Being tested: IncobotulinumtoxinA (100 Units), IncobotulinumtoxinA (75 Units), Placebo
Medical subject headings: Parkinson Disease, Brain Injuries, Traumatic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IncobotulinumtoxinA (100 Units)Drug
Also called Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
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).
IncobotulinumtoxinA (75 Units)Drug
Also called Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
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).
PlaceboDrug
Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).

Study groups in NCT02091739
Study group	Role	What they receive
IncobotulinumtoxinA (Xeomin) (100 Units)	Experimental	* 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) Receives: Drug: IncobotulinumtoxinA (100 Units)
IncobotulinumtoxinA (Xeomin) (75 Units)	Experimental	* 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) Receives: Drug: IncobotulinumtoxinA (75 Units)
Placebo	Placebo comparator	* 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) Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline and Week 4
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.
Measured: Week 4

Secondary outcomes (2)

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.
Measured: Baseline, Week 8 and 12
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.
Measured: Week 1, 2, 8, and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2014Nov 2016

First posted19 Mar 2014 (estimated)
Study startApr 2014
Primary completionAug 2015
Study completionNov 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Chronic Troublesome SialorrheaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 184 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02091739
Sponsor's protocol ID: MRZ60201_3090_1
Other IDs: 2012-005539-10
Acronym: SIAXI
Status last verified: Jan 2018
First submitted: 18 Mar 2014
Last updated: 27 Mar 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

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.
PubMed 31794936
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.
PubMed 30918101

Study at a glance

From the registry record, last updated by the sponsor on 27 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02091739
Acronym / sponsor ID: SIAXI / MRZ60201_3090_1
Conditions: Chronic Troublesome Sialorrhea, Parkinson's Disease, Post-stroke, Traumatic Brain Injury
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 184 participants (actual)
Lead sponsor: Merz Pharmaceuticals GmbHIndustry (pharma, biotech, devices)
Study start: Apr 2014
Primary completion: Aug 2015 (actual)
Study completion: Nov 2016 (actual)
First posted: 19 Mar 2014 (estimated)
Results: Posted 15 Feb 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
IncobotulinumtoxinA (Xeomin) (100 Units)	Experimental	Drug: IncobotulinumtoxinA (100 Units)* 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)
IncobotulinumtoxinA (Xeomin) (75 Units)	Experimental	Drug: IncobotulinumtoxinA (75 Units)* 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)
Placebo	Placebo comparator	Drug: Placebo* 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)

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

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 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.

Key exclusion criteria (8 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IncobotulinumtoxinA (100 Units)Also: Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteinsActive ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).	Drug	IncobotulinumtoxinA (Xeomin) (100 Units)
IncobotulinumtoxinA (75 Units)Also: Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteinsActive ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).	Drug	IncobotulinumtoxinA (Xeomin) (75 Units)
PlaceboSolution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).	Drug	Placebo

Primary outcome

MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 4
Time frame: Baseline and 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
Time frame: 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.

2 secondary outcomes

MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 8 and 12
Time frame: Baseline, Week 8 and 12
MP: Global Impression of Change Scale (GICS) at Week 1, 2, 8 and 12
Time frame: Week 1, 2, 8, and 12

Results and safety

Results posted to the registry on 15 Feb 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo	36	32
MP: IncobotulinumtoxinA (Xeomin) (75 Units)	74	69
MP: IncobotulinumtoxinA (Xeomin) (100 Units)	74	72
EP: IncobotulinumtoxinA (Xeomin) (75 Units)	0	0
EP: IncobotulinumtoxinA (Xeomin) (100 Units)	0	0

Primary outcome: MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 4

Time frame: Baseline and Week 4. Least squares mean (Standard Error). Unit: gram per minute (g/min)

Measure	MP: Placebo n = 36	MP: IncobotulinumtoxinA (Xeomin) (75 Units) n = 73	MP: IncobotulinumtoxinA (Xeomin) (100 Units) n = 73
Value	-0.04 (0.033)	-0.06 (0.027)	-0.13 (0.026)

MP: Placebo vs MP: IncobotulinumtoxinA (Xeomin) (100 Units): LS mean difference: -0.09 (95% CI -0.15 to 0.03), p = 0.004, MMRM
MP: Placebo vs MP: IncobotulinumtoxinA (Xeomin) (75 Units): LS mean difference: -0.02 (95% CI -0.08 to 0.04), p = 0.542, MMRM

Population analysed: 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.

Primary outcome: MP: Participant's Global Impression of Change Scale (GICS) at Week 4

Time frame: Week 4. Least squares mean (Standard Error). Unit: units on a scale

Measure	MP: Placebo n = 36	MP: IncobotulinumtoxinA (Xeomin) (75 Units) n = 74	MP: IncobotulinumtoxinA (Xeomin) (100 Units) n = 74
Value	0.67 (0.186)	1.02 (0.148)	1.25 (0.144)

MP: Placebo vs MP: IncobotulinumtoxinA (Xeomin) (100 Units): LS mean difference: 0.58 (95% CI 0.22 to 0.94), p = 0.002, MMRM
MP: Placebo vs MP: IncobotulinumtoxinA (Xeomin) (75 Units): LS mean difference: 0.35 (95% CI -0.01 to 0.71), p = 0.055, MMRM

Population analysed: The FAS is the subset of participants who were treated and had at least the baseline value of uSFR.

2 secondary outcomes are reported in the full results.

Adverse events

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).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo	3 of 36 (8.3%)	2 of 36 (5.6%)	0 of 36
MP: IncobotulinumtoxinA (Xeomin) (75 Units)	6 of 74 (8.1%)	14 of 74 (18.9%)	0 of 74
MP: IncobotulinumtoxinA (Xeomin) (100 Units)	9 of 74 (12.2%)	10 of 74 (13.5%)	0 of 74
EP: IncobotulinumtoxinA (Xeomin) (75 Units)	15 of 82 (18.3%)	22 of 82 (26.8%)	3 of 82
EP: IncobotulinumtoxinA (Xeomin) (100 Units)	14 of 89 (15.7%)	22 of 89 (24.7%)	2 of 89

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31794936Jost 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.
Derived from this study: PubMed 30918101Jost 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Merz Medical Expert study director

Merz Pharmaceuticals GmbH

31 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in Poland, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Feb 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 4 (time frame: Baseline and Week 4). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02091739, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2018.