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 (SIAXI)

Merz Pharmaceuticals

Status and phase: Completed; Phase 3

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

Treatments: Drug: IncobotulinumtoxinA (75 Units); Drug: IncobotulinumtoxinA (100 Units); Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02091739

MRZ60201_3090_1

2012-005539-10 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 184 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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184 participants in 3 patient groups, including a placebo group

IncobotulinumtoxinA (Xeomin) (100 Units)

Experimental group

Description:

* 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)

Treatment:

Drug: IncobotulinumtoxinA (100 Units)

IncobotulinumtoxinA (Xeomin) (75 Units)

Experimental group

Description:

* 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)

Treatment:

Drug: IncobotulinumtoxinA (75 Units)

Placebo

Placebo Comparator group

Description:

* 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)

Treatment:

Drug: Placebo