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

NCT02270736 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: MRZ60201_3091_12013-004532-30
• Study Type: interventional
• Target: 256
• Locations: 6 countries
• Sites: 31

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4

  This endpoint was planned to be analyzed in double-blind, MP, 6 to 17 years participants only. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and the procedure was repeated after 30 minutes. Salivary flow rate was equal to weight increase of swabs/time of collection. The average of the 2 results for flow rate was calculated. The reduction of measured weight over the study relates to improvement of sialorrhea.

  Baseline and Week 4

• Global Impression of Change Scale (GICS) at Week 4 Assessed by the Carer/Parent(s)

  This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. The GICS was used to measure the carer's/parent's impression of change due to treatment. The response option was a common 7-point Likert scale, with the following values: +3 (very much improved); +2 (much improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (much worse); -3 (very much worse).

  Week 4

• Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle

  Baseline up to Week 64

Secondary Outcomes (6)

• Change From Baseline in uSFR at Weeks 8 and 12

  Baseline and Weeks 8 and 12

• GICS at Weeks 8 and 12

  Weeks 8 and 12

• Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle

  Baseline up to Week 64

• Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle

  Baseline up to Week 64

• Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle

  Baseline up to Week 64

Study Arms (5)

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

EXPERIMENTAL

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.

Drug: NT 201 Placebo

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

EXPERIMENTAL

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.

Drug: NT 201

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

EXPERIMENTAL

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.

Drug: NT 201

OLEX: NT 201 (Age 6 to 17 Years)

EXPERIMENTAL

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)".

Drug: NT 201

OLEX: NT 201 (Age 2 to 5 Years)

EXPERIMENTAL

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).

Drug: NT 201

Interventions

NT 201 Placebo DRUG

NT 201 placebo matching injection.

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

NT 201 DRUG

NT 201 injection.

Also known as: IncobotulinumtoxinA, Xeomin, Botulinum toxin type A (150 kiloDalton), free from complexing proteins

Double-blind, MP: NT 201 (Age 6 to 17 Years); OLEX: NT 201 (Age 2 to 5 Years); OLEX: NT 201 (Age 6 to 17 Years); Open-label, MP: NT 201 (Age 2 to 5 Years)

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female child/adolescent age 2-17 years.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merz Pharmaceuticals GmbH: lead

Study Sites (31)

Merz Investigational Site #9950003

K'obulet'i, 6200, Georgia

Location

Merz Investigational Site #9950001

Tbilisi, 0159, Georgia

Location

Merz Investigational Site #9950002

Tbilisi, 0159, Georgia

Location

Merz Investigational Site #0360017

Balassagyarmat, 2660, Hungary

Location

Merz Investigational Site #0360013

Budapest, 1083, Hungary

Location

Merz Investigational Site # 0360014

Budapest, 1125, Hungary

Location

Merz Investigational Site # 0360015

Budapest, 1125, Hungary

Location

Merz Investigational Site #0360018

Budapest, 1146, Hungary

Location

Merz Investigational Site #0360016

Szombathely, 9700, Hungary

Location

Merz Investigational Site #0480092

Bialystok, 15-274, Poland

Location

Merz Investigational Site #0480090

Gdansk, 80-952, Poland

Location

Merz Investigational Site #0480076

Katowice, 40-954, Poland

Location

Merz Investigational Site #0480059

Krakow, 30-359, Poland

Location

Merz Investigational Site #0480060

Wiązowna, 05-462, Poland

Location

Merz Investigational Site #0070016

Kazan', 420012, Russia

Location

Merz Investigational Site # 0070288

Kemerovo, 650066, Russia

Location

Merz Investigational Site #0070290

Khabarovsk, 680038, Russia

Location

Merz Investigational # 0070017

Saint Petersburg, 194100, Russia

Location

Merz Investigational Site #0070013

Smolensk, 214018, Russia

Location

Merz Investigational Site # 070019

Stavropol, 355029, Russia

Location

Merz Investigational Site #0070300

Tomsk, 634052, Russia

Location

Merz Investigational Site #0070301

Yekaterinburg, 620149, Russia

Location

Merz Investigational Site #3810001

Belgrade, 11040, Serbia

Location

Merz Investigational Site #3800001

Dnipropetrovsk, 49027, Ukraine

Location

Merz Investigational Site #3800012

Ivano-Frankivsk, 76014, Ukraine

Location

Merz Investigational Site #3800005

Kharkiv, 61068, Ukraine

Location

Merz Investigational Site #3800007

Kharkiv, 61153, Ukraine

Location

Merz Investigational Site #3800013

Kherson, 73010, Ukraine

Location

Merz Investigational site #3800003

Odesa, 65012, Ukraine

Location

Merz Investigational Site #3800009

Ternopil, 46020, Ukraine

Location

Merz Investigational Site #3800011

Zaporizhzhya, 69063, Ukraine

Location

Related Publications (2)

• Berweck S, Bonikowski M, Kim H, Althaus M, Flatau-Baque B, Mueller D, Banach MD. Placebo-Controlled Clinical Trial of IncobotulinumtoxinA for Sialorrhea in Children: SIPEXI. Neurology. 2021 Oct 4;97(14):e1425-e1436. doi: 10.1212/WNL.0000000000012573.

  PMID: 34341153 RESULT

• Berweck S, Banach M, Gaebler-Spira D, Chambers HG, Schroeder AS, Geister TL, Althaus M, Hanschmann A, Vacchelli M, Bonfert MV, Heinen F, Dabrowski E. Safety Profile and Lack of Immunogenicity of IncobotulinumtoxinA in Pediatric Spasticity and Sialorrhea: A Pooled Analysis. Toxins (Basel). 2022 Aug 25;14(9):585. doi: 10.3390/toxins14090585.

  PMID: 36136523 DERIVED

MeSH Terms

Conditions

Cerebral Palsy; Stroke; Brain Injuries, Traumatic; Intellectual Disability

Interventions

incobotulinumtoxinA; Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Brain Injuries; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Public Disclosure Manager
• Organization: Merz Pharmaceuticals GmbH

clinicaltrials@merz.com

+49 69 1503 1

Study Officials

• Merz Medical Expert

  Merz Pharmaceuticals GmbH

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: October 21, 2014
• Study Start: February 9, 2015
• Primary Completion: February 23, 2018
• Study Completion: May 7, 2019
• Last Updated: August 10, 2021
• Results First Posted: January 20, 2021

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

UA (8); PL (5); RU (8); HU (6); GE (3); SE (1)