Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability (SIPEXI)

Merz Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Traumatic Brain Injury; Stroke; Cerebral Palsy; Chronic Troublesome Sialorrhea; Intellectual Disability

Treatments: Drug: NT 201 Placebo; Drug: NT 201

Study type: Interventional

Funder types: Industry

Identifiers

NCT02270736

MRZ60201_3091_1

2013-004532-30 (EudraCT Number)

Details and patient eligibility

About

The objective of this study is to investigate the efficacy and safety of NT 201 compared with placebo for the treatment of chronic troublesome sialorrhea associated with neurological disorders (e.g. cerebral palsy, traumatic brain injury) and/or intellectual disability in children and adolescents naïve to Botulinum neurotoxin treatment and aged 2-17 years.

Enrollment: 256 patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female child/adolescent age 2-17 years.
• Any neurological disorder (e.g. cerebral palsy or traumatic brain injury) and/or intellectual disability associated with chronic troublesome sialorrhea for at least 3 months up to the screening. In subjects with intellectual disability (ID) without neurological disorders, a diagnosis of ID by a specialist, e.g. pediatrician or by a center for developmental medicine is required for inclusion.
• Severe drooling (modified Teacher´s Drooling Scale [mTDS] ≥ 6; clothing occasionally becomes damp) as rated by the investigator.
• Parental consent and the subject's oral or written assent as the subject is able to provide.

Exclusion criteria

• Chronic troublesome sialorrhea not related to neurological disorders and/or intellectual disability.
• Body weight < 12 kg.
• Pharmacological treatment for sialorrhea or concomitant medication known to influence sialorrhea strongly (e.g. anticholinergics with exception of locally applied or short acting drugs used under general anesthesia) within 45 days before baseline and during the entire study period.
• Any previous known or suspected hypersensitivity to Botulinum toxin.
• Aspiration pneumonia within 6 month before screening.
• Any previous treatment with Botulinum toxin for any body region during the year before screening or within the screening period
• Prior, concomitant or planned surgery or irradiation to head and neck to control sialorrhea (including salivary gland surgery or salivary gland irradiation) within one year before screening or planned for any part of the entire study period.
• Concurrent diseases, including hematological, hepatic, renal, gastrointestinal, endocrine, pulmonary, musculoskeletal, or psychiatric diseases or conditions, which in the judgment of the investigator would put the subject at risk while in the study, could influence the results of the study, or negatively impact the subject's ability to participate in the study.
• Extremely poor dental and/or oral condition that might preclude safe study participation by the judgment of the investigator.
• Nursing mother or pregnant female subject.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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256 participants in 5 patient groups

Double-blind MP: Placebo (Age 6 to 17 Years)

Experimental group

Description:

Participants will receive placebo via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks. Volumes will be matched to the volumes of NT 201 (incobotulinumtoxinA; Xeomin) injected in the experimental arm.

Treatment:

Drug: NT 201 Placebo

Double-blind, MP: NT 201 (Age 6 to 17 Years)

Experimental group

Description:

Participants will receive NT 201 (up to 2.5 Units per kilogram \[U/kg\] body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.

Treatment:

Drug: NT 201

Open-label, MP: NT 201 (Age 2 to 5 Years)

Experimental group

Description:

Participants will receive NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands in one injection session on Day 1 (Visit 2) of the MP, followed by an observation period of 16 weeks.

Treatment:

Drug: NT 201

OLEX: NT 201 (Age 6 to 17 Years)

Experimental group

Description:

Participants will receive NT 201 (up to 2.5 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total). This arm will consist of participants who will participate in MP arms "Double-blind, MP: placebo (age 6 to 17 years)" and "Double-blind, MP: NT 201 (age 6 to 17 years)".

Treatment:

Drug: NT 201

OLEX: NT 201 (Age 2 to 5 Years)

Experimental group

Description:

Participants will receive NT 201 (about 1.5-2 U/kg body weight) via bilateral intraglandular injection into the parotid and submandibular glands on Day 1 of second (Visit 6), third (Visit 10), and fourth (Visit 14) injection cycle of the OLEX, followed by an observation period of 16 weeks each (48 weeks in total).

Treatment:

Drug: NT 201