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

Stroke Clinical Trial

— SIPEXI  

Official title:

Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study With an Open-label Extension Period to Investigate the Efficacy and Safety of NT 201 in the Treatment of Children and Adolescents (2-17 Years) With Chronic Troublesome Sialorrhea Associated With Neurological Disorders, and/or Intellectual Disability

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02270736
• Other study ID #: MRZ60201_3091_1
• Secondary ID: 2013-004532-30
• Status: Completed
• Phase: Phase 3
• Start date: February 9, 2015
• Est. completion date: May 7, 2019

Study information

• Verified date: July 2019
• Source: Merz Pharmaceuticals GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 256
• Est. completion date: May 7, 2019
• Est. primary completion date: February 23, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Cerebral Palsy
• Chronic Troublesome Sialorrhea
• Intellectual Disability
• Nervous System Diseases
• Sialorrhea
• Stroke
• Traumatic Brain Injury

Intervention

Drug:
• NT 201 Placebo
NT 201 placebo matching injection.
• NT 201
NT 201 injection.

Locations

Country	Name	City	State
Georgia	Merz Investigational Site #9950003	Kobuleti
Georgia	Merz Investigational Site #9950001	Tbilisi
Georgia	Merz Investigational Site #9950002	Tbilisi
Hungary	Merz Investigational Site #0360017	Balassagyarmat
Hungary	Merz Investigational Site # 0360014	Budapest
Hungary	Merz Investigational Site # 0360015	Budapest
Hungary	Merz Investigational Site #0360013	Budapest
Hungary	Merz Investigational Site #0360018	Budapest
Hungary	Merz Investigational Site #0360016	Szombathely
Poland	Merz Investigational Site #0480092	Bialystok
Poland	Merz Investigational Site #0480090	Gdansk
Poland	Merz Investigational Site #0480076	Katowice
Poland	Merz Investigational Site #0480059	Krakow
Poland	Merz Investigational Site #0480060	Wiazowna
Russian Federation	Merz Investigational Site #0070016	Kazan
Russian Federation	Merz Investigational Site # 0070288	Kemerovo
Russian Federation	Merz Investigational Site #0070290	Khabarovsk
Russian Federation	Merz Investigational # 0070017	Saint Petersburg
Russian Federation	Merz Investigational Site #0070013	Smolensk
Russian Federation	Merz Investigational Site # 070019	Stavropol
Russian Federation	Merz Investigational Site #0070300	Tomsk
Russian Federation	Merz Investigational Site #0070301	Yekaterinburg
Serbia	Merz Investigational Site #3810001	Belgrade
Ukraine	Merz Investigational Site #3800001	Dnipropetrovsk
Ukraine	Merz Investigational Site #3800012	Ivano-Frankivsk
Ukraine	Merz Investigational Site #3800005	Kharkiv
Ukraine	Merz Investigational Site #3800007	Kharkiv
Ukraine	Merz Investigational Site #3800013	Kherson
Ukraine	Merz Investigational site #3800003	Odesa
Ukraine	Merz Investigational Site #3800009	Ternopil
Ukraine	Merz Investigational Site #3800011	Zaporizhzhya

Sponsors (1)

Lead Sponsor	Collaborator
Merz Pharmaceuticals GmbH

Countries where clinical trial is conducted

Georgia,  Hungary,  Poland,  Russian Federation,  Serbia,  Ukraine, 

References & Publications (1)

Berweck S, Bonikowski M, Kim H, Althaus M, Flatau-Baqué B, Mueller D, Banach MD. Placebo-Controlled Clinical Trial of IncobotulinumtoxinA for Sialorrhea in Children: SIPEXI. Neurology. 2021 Aug 2. pii: 10.1212/WNL.0000000000012573. doi: 10.1212/WNL.000000 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Occurrence of Treatment Emergent Adverse Events (TEAEs) Overall and Per Injection Cycle		Baseline up to Week 64
Secondary	Change From Baseline in uSFR at 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.	Baseline and Weeks 8 and 12
Secondary	GICS at 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).	Weeks 8 and 12
Secondary	Occurrence of Treatment Emergent Adverse Events of Special Interest (AESI) Overall and by Injection Cycle		Baseline up to Week 64
Secondary	Occurrence of Treatment Emergent Serious Adverse Events (TESAEs) Overall and by Injection Cycle		Baseline up to Week 64
Secondary	Occurrence of TEAEs Related to Treatment as Assessed by the Investigator Overall and by Injection Cycle		Baseline up to Week 64
Secondary	Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle		Baseline up to Week 64