Clinical trial NCT02091739: 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
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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Troublesome Sialorrhea
Parkinson's Disease
Post-stroke
Traumatic Brain Injury
Lead sponsor: Merz Pharmaceuticals GmbH
Sponsor class: INDUSTRY
First posted: 2014-03-19
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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):

  1. A Drooling Severity and Frequency Scale \[DSFS\] sum score of at least 6 points and
  2. A score of at least 2 points for each item of the DSFS and
  3. 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.

Primary outcomes:
measure: MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 4
timeFrame: Baseline and Week 4
measure: MP: Participant's Global Impression of Change Scale (GICS) at Week 4
timeFrame: Week 4
Secondary outcomes:
measure: MP: Change From Baseline in Unstimulated Salivary Flow (uSFR) Rate at Week 8 and 12
timeFrame: Baseline, Week 8 and 12
measure: MP: Global Impression of Change Scale (GICS) at Week 1, 2, 8 and 12
timeFrame: Week 1, 2, 8, and 12
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: Merz investigational site #049172
city: Gera
country: Germany
facility: Merz Investigational Site #049335
city: Haag i.OB
country: Germany
facility: Merz Investigational Site #049337
city: Munich
country: Germany
facility: Merz Investigational Site #049072
city: Munich
country: Germany
facility: Merz Investigational Site #049148
city: Nümbrecht
country: Germany
facility: Merz Investigational Site #049300
city: Regensburg
country: Germany
facility: Merz Investigational Site #049303
city: Stadtroda
country: Germany
facility: Merz investigational site #049348
city: Ulm
country: Germany
facility: Merz Investigational Site #049143
city: Wolfach
country: Germany
facility: Merz Investigational Site #049333
city: Wuerzburg
country: Germany
facility: Merz Investigational Site #049302
city: Bydgoszcz
country: Poland
facility: Merz investigational site #048068
city: Bydgoszcz
country: Poland
facility: Merz Investigational Site #048088
city: Gdansk
country: Poland
facility: Merz Investigational Site #048029
city: Gdansk
country: Poland
facility: Merz investigational site #048074
city: Jaworzno
country: Poland
facility: Merz investigational site #048078
city: Katowice
country: Poland
facility: Merz investigational site #048076
city: Katowice
country: Poland
facility: Merz investigational site #048077
city: Kielce
country: Poland
facility: Merz investigational Site #048067
city: Krakow
country: Poland
facility: Merz investigational site #048059
city: Krakow
country: Poland
facility: Merz investigational site #048031
city: Krakow
country: Poland
facility: Merz Investigational Site #048087
city: Lodz
country: Poland
facility: Merz Investigational Site #048022
city: Lublin
country: Poland
facility: Merz investigational site #048070
city: Lublin
country: Poland
facility: Merz investigational site #048085
city: Lubon
country: Poland
facility: Merz investigational site #048072
city: Sandomierz
country: Poland
facility: Merz Investigational Site #048075
city: Torun
country: Poland
facility: Merz Investigational Site #048086
city: Warszawa
country: Poland
facility: Merz investigational site #048065
city: Warszawa
country: Poland
facility: Merz investigational site #048056
city: Warszawa
country: Poland
facility: Merz investigational site #048064
Study officials:
affiliation: Merz Pharmaceuticals GmbH
name: Merz Medical Expert
role: STUDY_DIRECTOR
References:
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.
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.