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

Study Overview
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Brief Summary
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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.

Official Title
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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
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Chronic Troublesome Sialorrhea, Parkinson's Disease, Post-stroke, Traumatic Brain Injury

Intervention / Treatment
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* Drug: IncobotulinumtoxinA (100 Units)
* Drug: IncobotulinumtoxinA (75 Units)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IncobotulinumtoxinA (Xeomin) (100 Units)<br>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)<br>* 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).<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing proteins;|
| Experimental: IncobotulinumtoxinA (Xeomin) (75 Units)<br>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)<br>* 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).<br>* Other names: Botulinum toxin type A (150 kiloDalton), free from complexing proteins;|
| Placebo Comparator: Placebo<br>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<br>* Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | Week 1, 2, 8, and 12 |