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

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

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.

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.