NCT02091739

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
184

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Apr 2014

Typical duration for phase_3

Geographic Reach
2 countries

31 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 18, 2014

Completed
1 day until next milestone

First Posted

Study publicly available on registry

March 19, 2014

Completed
13 days until next milestone

Study Start

First participant enrolled

April 1, 2014

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2015

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2016

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

February 15, 2018

Completed
Last Updated

March 27, 2018

Status Verified

January 1, 2018

Enrollment Period

1.3 years

First QC Date

March 18, 2014

Results QC Date

January 15, 2018

Last Update Submit

February 27, 2018

Conditions

Chronic Troublesome SialorrheaParkinson's DiseasePost-strokeTraumatic Brain Injury

Outcome Measures

Primary Outcomes (2)

  • 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.

    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.

    Week 4

Secondary Outcomes (2)

  • MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 8 and 12

    Baseline, Week 8 and 12

  • MP: Global Impression of Change Scale (GICS) at Week 1, 2, 8 and 12

    Week 1, 2, 8, and 12

Study Arms (3)

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)

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)

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)

Drug: Placebo

Interventions

IncobotulinumtoxinA (100 Units)DRUG

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).

Also known as: Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
IncobotulinumtoxinA (Xeomin) (100 Units)
IncobotulinumtoxinA (75 Units)DRUG

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).

Also known as: Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
IncobotulinumtoxinA (Xeomin) (75 Units)
PlaceboDRUG

Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).

Placebo

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (31)

Merz investigational site #049172

Bonn, 53105, Germany

Location

Merz Investigational Site #049335

Gera, 07551, Germany

Location

Merz Investigational Site #049337

Haag i.OB, 83527, Germany

Location

Merz Investigational Site #049072

Munich, 80804, Germany

Location

Merz Investigational Site #049148

Munich, 81675, Germany

Location

Merz Investigational Site #049300

Nümbrecht, 51588, Germany

Location

Merz Investigational Site #049303

Regensburg, 93053, Germany

Location

Merz investigational site #049348

Stadtroda, 07646, Germany

Location

Merz Investigational Site #049143

Ulm, 89081, Germany

Location

Merz Investigational Site #049333

Wolfach, 77709, Germany

Location

Merz Investigational Site #049302

Würzburg, 97080, Germany

Location

Merz investigational site #048068

Bydgoszcz, 85-015, Poland

Location

Merz Investigational Site #048088

Bydgoszcz, 85-080, Poland

Location

Merz Investigational Site #048029

Gdansk, 80-254, Poland

Location

Merz investigational site #048074

Gdansk, 80-546, Poland

Location

Merz investigational site #048078

Jaworzno, 43-600, Poland

Location

Merz investigational site #048076

Katowice, 40-097, Poland

Location

Merz investigational site #048077

Katowice, 40-097, Poland

Location

Merz investigational Site #048067

Kielce, 25-103, Poland

Location

Merz investigational site #048059

Krakow, 30-539, Poland

Location

Merz investigational site #048031

Krakow, 31-505, Poland

Location

Merz Investigational Site #048087

Krakow, 31-530, Poland

Location

Merz Investigational Site #048022

Lodz, 90-130, Poland

Location

Merz investigational site #048070

Lublin, 20-718, Poland

Location

Merz investigational site #048085

Lublin, 30-539, Poland

Location

Merz investigational site #048072

Luboń, 62-030, Poland

Location

Merz Investigational Site #048075

Sandomierz, 27-600, Poland

Location

Merz Investigational Site #048086

Torun, 87-100, Poland

Location

Merz investigational site #048065

Warsaw, 00-453, Poland

Location

Merz investigational site #048056

Warsaw, 02-097, Poland

Location

Merz investigational site #048064

Warsaw, 03-242, Poland

Location

Related Publications (2)

  • 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.

    PMID: 31794936DERIVED

  • 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.

    PMID: 30918101DERIVED

MeSH Terms

Conditions

Parkinson DiseaseBrain Injuries, Traumatic

Interventions

incobotulinumtoxinABotulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Parkinsonian DisordersBasal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersSynucleinopathiesNeurodegenerative DiseasesBrain InjuriesCraniocerebral TraumaTrauma, Nervous SystemWounds and Injuries

Intervention Hierarchy (Ancestors)

Botulinum ToxinsMetalloendopeptidasesEndopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesMetalloproteasesBacterial ProteinsProteinsAmino Acids, Peptides, and ProteinsBacterial ToxinsToxins, BiologicalBiological Factors

Results Point of Contact

Title
Public Disclosure Manager
Organization
Merz Pharmaceuticals GmbH
clinicaltrials@merz.de
+49 69 1503 1

Study Officials

  • Merz Medical Expert

    Merz Pharmaceuticals GmbH

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 18, 2014

First Posted

March 19, 2014

Study Start

April 1, 2014

Primary Completion

August 1, 2015

Study Completion

November 1, 2016

Last Updated

March 27, 2018

Results First Posted

February 15, 2018

Record last verified: 2018-01

Locations

PL(20)DE(11)