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

Phase 3

Completed

• Conditions: Chronic Troublesome Sialorrhea; Stroke; Traumatic Brain Injury; Intellectual Disability; Cerebral Palsy
• Interventions: Drug: NT 201 Placebo; Drug: NT 201

• Registration Number: NCT02270736
• Lead Sponsor: Merz Pharmaceuticals GmbH

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-10-17
• Study First Submitted QC: 2014-10-17
• Study First Posted: 2014-10-21
• Study Start: 2015-02-09
• Primary Completion: 2018-02-23
• Disposition First Submitted: 2019-02-20
• Disposition First Submitted QC: 2019-02-20
• Disposition First Posted: 2019-02-21
• Study Completion: 2019-05-07
• Status Verified: 2019-07
• Results First Submitted: 2020-12-23
• Results First Submitted QC: 2020-12-23
• Results First Posted: 2021-01-20
• Last Update Submitted: 2021-08-06
• Last Update Posted: 2021-08-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 256

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.

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Double-blind MP: Placebo (Age 6 to 17 Years)	NT 201 Placebo	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.
OLEX: NT 201 (Age 2 to 5 Years)	NT 201	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).
Double-blind, MP: NT 201 (Age 6 to 17 Years)	NT 201	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.
Open-label, MP: NT 201 (Age 2 to 5 Years)	NT 201	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.
OLEX: NT 201 (Age 6 to 17 Years)	NT 201	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)".

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4	Baseline and 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.
Global Impression of Change Scale (GICS) at Week 4 Assessed by the Carer/Parent(s)	Week 4	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).
Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle	Baseline up to Week 64

Secondary Outcome Measures

Name	Time	Method
Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle	Baseline up to Week 64
GICS at Weeks 8 and 12	Weeks 8 and 12	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).
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
Change From Baseline in uSFR at Weeks 8 and 12	Baseline and Weeks 8 and 12	This endpoint was analyzed in double-blind, MP, 6 to 17 years participants. uSFR was assessed by weighing of absorbent swabs with safety threads soaked with saliva over 5 minutes and then 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.
Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle	Baseline up to Week 64

Trial Locations

Locations (31)

Merz Investigational Site #9950001; 🇬🇪 Tbilisi, Georgia

Merz Investigational Site #3800001; 🇺🇦 Dnipropetrovsk, Ukraine

Merz Investigational site #3800003; 🇺🇦 Odesa, Ukraine

Merz Investigational Site #3800013; 🇺🇦 Kherson, Ukraine

Merz Investigational Site #0360017; 🇭🇺 Balassagyarmat, Hungary

Merz Investigational Site #0480059; 🇵🇱 Krakow, Poland

Merz Investigational Site # 0070288; 🇷🇺 Kemerovo, Russian Federation

Merz Investigational Site #0480092; 🇵🇱 Bialystok, Poland

Merz Investigational Site #0480060; 🇵🇱 Wiazowna, Poland

Merz Investigational Site #0070013; 🇷🇺 Smolensk, Russian Federation

Merz Investigational Site #0070301; 🇷🇺 Yekaterinburg, Russian Federation

Merz Investigational Site #3810001; 🇷🇸 Belgrade, Serbia

Merz Investigational Site # 0360015; 🇭🇺 Budapest, Hungary

Merz Investigational Site #0480076; 🇵🇱 Katowice, Poland

Merz Investigational Site #0360013; 🇭🇺 Budapest, Hungary

Merz Investigational Site # 070019; 🇷🇺 Stavropol, Russian Federation

Merz Investigational Site #3800009; 🇺🇦 Ternopil, Ukraine

Merz Investigational Site #3800011; 🇺🇦 Zaporizhzhya, Ukraine

Merz Investigational Site #9950003; 🇬🇪 Kobuleti, Georgia

Merz Investigational Site #9950002; 🇬🇪 Tbilisi, Georgia

Merz Investigational Site #0360018; 🇭🇺 Budapest, Hungary

Merz Investigational Site # 0360014; 🇭🇺 Budapest, Hungary

Merz Investigational Site #0360016; 🇭🇺 Szombathely, Hungary

Merz Investigational Site #0480090; 🇵🇱 Gdansk, Poland

Merz Investigational Site #0070016; 🇷🇺 Kazan, Russian Federation

Merz Investigational # 0070017; 🇷🇺 Saint Petersburg, Russian Federation

Merz Investigational Site #0070300; 🇷🇺 Tomsk, Russian Federation

Merz Investigational Site #0070290; 🇷🇺 Khabarovsk, Russian Federation

Merz Investigational Site #3800012; 🇺🇦 Ivano-Frankivsk, Ukraine

Merz Investigational Site #3800005; 🇺🇦 Kharkiv, Ukraine

Merz Investigational Site #3800007; 🇺🇦 Kharkiv, Ukraine