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

NCT ID: NCT02091739

Last Updated: 2018-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 184 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2016-11-30

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.

Conditions

Chronic Troublesome Sialorrhea; Parkinson's Disease; Post-stroke; Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

IncobotulinumtoxinA (Xeomin) (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)

Group Type: EXPERIMENTAL

IncobotulinumtoxinA (100 Units)

Intervention Type: 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).

IncobotulinumtoxinA (Xeomin) (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)

Group Type: EXPERIMENTAL

IncobotulinumtoxinA (75 Units)

Intervention Type: 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).

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)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

IncobotulinumtoxinA (100 Units)

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

IncobotulinumtoxinA (75 Units)

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

Placebo

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

Intervention Type: DRUG

Other Intervention Names

Xeomin; NT 201; Botulinum toxin type A (150 kiloDalton), free from complexing proteins; Xeomin; NT 201; Botulinum toxin type A (150 kiloDalton), free from complexing proteins

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merz Pharmaceuticals GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Merz Medical Expert

Role: STUDY_DIRECTOR

Merz Pharmaceuticals GmbH

Locations

Merz investigational site #049172

Bonn, , Germany

Merz Investigational Site #049335

Gera, , Germany

Merz Investigational Site #049337

Haag i.OB, , Germany

Merz Investigational Site #049072

Munich, , Germany

Merz Investigational Site #049148

Munich, , Germany

Merz Investigational Site #049300

Nümbrecht, , Germany

Merz Investigational Site #049303

Regensburg, , Germany

Merz investigational site #049348

Stadtroda, , Germany

Merz Investigational Site #049143

Ulm, , Germany

Merz Investigational Site #049333

Wolfach, , Germany

Merz Investigational Site #049302

Würzburg, , Germany

Merz investigational site #048068

Bydgoszcz, , Poland

Merz Investigational Site #048088

Bydgoszcz, , Poland

Merz Investigational Site #048029

Gdansk, , Poland

Merz investigational site #048074

Gdansk, , Poland

Merz investigational site #048078

Jaworzno, , Poland

Merz investigational site #048076

Katowice, , Poland

Merz investigational site #048077

Katowice, , Poland

Merz investigational Site #048067

Kielce, , Poland

Merz investigational site #048059

Krakow, , Poland

Merz investigational site #048031

Krakow, , Poland

Merz Investigational Site #048087

Krakow, , Poland

Merz Investigational Site #048022

Lodz, , Poland

Merz investigational site #048070

Lublin, , Poland

Merz investigational site #048085

Lublin, , Poland

Merz investigational site #048072

Luboń, , Poland

Merz Investigational Site #048075

Sandomierz, , Poland

Merz Investigational Site #048086

Torun, , Poland

Merz investigational site #048065

Warsaw, , Poland

Merz investigational site #048056

Warsaw, , Poland

Merz investigational site #048064

Warsaw, , Poland

Countries

Germany; Poland

References

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.

Reference Type: DERIVED

PMID: 31794936 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30918101 (View on PubMed)

Other Identifiers

2012-005539-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MRZ60201_3090_1

Identifier Type: -

Identifier Source: org_study_id