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Chronic Troublesome SialorrheaPhase 3SIPEXINCT02270736

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

A Phase 3 study testing NT 201 in people with Chronic Troublesome Sialorrhea and Cerebral Palsy, run by Merz Pharmaceuticals GmbH at 31 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 2 to 17 years
What is being tested?
NT 201
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
256 participants
Where
31 sitesin 6 countries
Study dates
9 Feb 2015to 7 May 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 10Show fewer
  • 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 locations and contacts

31 sites in 6 countries.

31 sites in 6 countries

Russia8 sites
  • Merz Investigational Site #0070016

    Kazan', 420012

  • Merz Investigational Site # 0070288

    Kemerovo, 650066

  • Merz Investigational Site #0070290

    Khabarovsk, 680038

  • Merz Investigational # 0070017

    Saint Petersburg, 194100

  • Merz Investigational Site #0070013

    Smolensk, 214018

  • Merz Investigational Site # 070019

    Stavropol, 355029

  • Merz Investigational Site #0070300

    Tomsk, 634052

  • Merz Investigational Site #0070301

    Yekaterinburg, 620149

Other trials in Russia

Ukraine8 sites
  • Merz Investigational Site #3800001

    Dnipropetrovsk, 49027

  • Merz Investigational Site #3800012

    Ivano-Frankivsk, 76014

  • Merz Investigational Site #3800005

    Kharkiv, 61068

  • Merz Investigational Site #3800007

    Kharkiv, 61153

  • Merz Investigational Site #3800013

    Kherson, 73010

  • Merz Investigational site #3800003

    Odesa, 65012

  • Merz Investigational Site #3800009

    Ternopil, 46020

  • Merz Investigational Site #3800011

    Zaporizhzhya, 69063

Other trials in Ukraine

Hungary6 sites
  • Merz Investigational Site #0360017

    Balassagyarmat, 2660

  • Merz Investigational Site #0360013

    Budapest, 1083

  • Merz Investigational Site # 0360014

    Budapest, 1125

  • Merz Investigational Site # 0360015

    Budapest, 1125

  • Merz Investigational Site #0360018

    Budapest, 1146

  • Merz Investigational Site #0360016

    Szombathely, 9700

Other trials in Hungary

Poland5 sites
  • Merz Investigational Site #0480092

    Bialystok, 15-274

  • Merz Investigational Site #0480090

    Gdansk, 80-952

  • Merz Investigational Site #0480076

    Katowice, 40-954

  • Merz Investigational Site #0480059

    Krakow, 30-359

  • Merz Investigational Site #0480060

    Wiązowna, 05-462

Other trials in Poland

Georgia3 sites
  • Merz Investigational Site #9950003

    K'obulet'i, 6200

  • Merz Investigational Site #9950001

    Tbilisi, 0159

  • Merz Investigational Site #9950002

    Tbilisi, 0159

Other trials in Georgia

Serbia1 site
  • Merz Investigational Site #3810001

    Belgrade, 11040

Other trials in Serbia

About this study

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

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.

Being tested
NT 201 Placebo, NT 201
Medical subject headings
Cerebral Palsy, Stroke, Brain Injuries, Traumatic, Intellectual Disability

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NT 201 PlaceboDrug

    NT 201 placebo matching injection.

  • NT 201Drug

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

    NT 201 injection.

Study groups in NCT02270736
Study groupRoleWhat they receive
Double-blind MP: Placebo (Age 6 to 17 Years)ExperimentalParticipants 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.
Receives: Drug: NT 201 Placebo
Double-blind, MP: NT 201 (Age 6 to 17 Years)ExperimentalParticipants 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.
Receives: Drug: NT 201
Open-label, MP: NT 201 (Age 2 to 5 Years)ExperimentalParticipants 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.
Receives: Drug: NT 201
OLEX: NT 201 (Age 6 to 17 Years)ExperimentalParticipants 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)".
Receives: Drug: NT 201
OLEX: NT 201 (Age 2 to 5 Years)ExperimentalParticipants 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).
Receives: Drug: NT 201

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline and Week 4

  2. 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).

    Measured: Week 4

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

    Measured: Baseline up to Week 64

Secondary outcomes (6)
  1. 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.

    Measured: Baseline and Weeks 8 and 12

  2. 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).

    Measured: Weeks 8 and 12

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

    Measured: Baseline up to Week 64

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

    Measured: Baseline up to Week 64

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

    Measured: Baseline up to Week 64

  6. Occurrence of TEAEs Leading to Discontinuation Overall and by Injection Cycle

    Measured: Baseline up to Week 64

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Oct 2014 (estimated)
  2. Study start9 Feb 2015
  3. Primary completion23 Feb 2018
  4. Study completion7 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
256 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02270736
Sponsor's protocol ID
MRZ60201_3091_1
Other IDs
2013-004532-30
Acronym
SIPEXI
Status last verified
Jul 2019
First submitted
17 Oct 2014
Last updated
10 Aug 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 34341153
  • 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.

    PubMed 36136523

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing NT 201 in people with Chronic Troublesome Sialorrhea and Cerebral Palsy, run by Merz Pharmaceuticals GmbH at 31 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 31 sites in Russia, Ukraine, Hungary, Poland, Georgia and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Unstimulated Salivary Flow Rate (uSFR) at Week 4 (time frame: Baseline and Week 4). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02270736, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2021.

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