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Botulinum Toxin A to Treat Arm Tremor

Primary Purpose

Essential Tremor of the Upper Limbs

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IncobotulinumtoxinA
Placebo
Sponsored by
Merz Pharmaceuticals GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Essential Tremor of the Upper Limbs

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Main Inclusion Criteria:

  • Diagnosis of 'definite essential tremor' in accordance with modified TRIG criteria, as follows:

    • Bilateral postural tremor with or without kinetic tremor, involving hands and forearms, that is visible and persistent.
    • It is to be noted that:
    • Tremor of other body parts may be present in addition to upper limb tremor.
    • Bilateral tremor may be asymmetric.
    • Tremor is reported by patient to be persistent, although the amplitude may fluctuate.
  • First onset of essential tremor at least 6 months before screening with stability of the tremor symptoms over 4 weeks and in the opinion of the investigator definite diagnosis of essential tremor.
  • Moderate-to-marked upper-limb postural and/or kinetic tremor at wrist level, corresponding to Fahn-Tolosa-Marin upper-limb tremor rating of at least 2 categories (scale part C, items 16-23) in the limb to be treated between of 2 or higher.
  • Visible tremor at wrist level in at least one of the four positions/tasks used in kinematic assessments
  • Tremor deemed by the investigator to require a treatment with 30 - 200 U NT 201 for a treatment of up to three joints of the selected upper limb (wrist treatment mandatory).
  • Stable concomitant anti-tremor medication and no clinically relevant findings in routine laboratory examinations.

Main Exclusion Criteria:

  • Any neurological signs abnormal for the subject's age, other than the tremor itself and Froment's maneuver.
  • Exposure to the following tremorogenic drugs: Lithium, Valproic acid, Amiodarone, typical and atypical neuroleptics. Exposure to other than the listed tremorogenic or potentially tremorogenic drugs is allowed only if, in the opinion of the investigator, this will not interfere with the study drug evaluation. In these cases, a stable medication should be reached 4 weeks before screening and intended for the time during the study drug evaluation.
  • Trauma to the central nervous system or the nerves of the target limb within the three months preceding the onset of tremor.
  • Evidence of psychogenic origins of tremor.
  • Life habits (e.g. smoking, alcohol or substance abuse) prejudicial to study participation.
  • Prior surgery to treat tremor
  • Recent (16 weeks) treatment with any Botulinum toxin product for any reason.
  • Relevant recent or planned surgery or other specified relevant treatments and/or concomitant disorders.

Sites / Locations

  • Merz Investigational Site #0010191
  • Merz Investigational Site #0010317
  • Merz Investigational Site #0010089
  • Merz Investigational Site #0010078
  • Merz Investigational Site #0010305/1
  • Merz Investigational Site #0010305/2

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

200 Units incobotulinumtoxinA (Xeomin)

Placebo

Arm Description

Single injection cycle, total dose of up to 200 Units, intramuscular injection into muscles of wrist (mandatory) and shoulder and/or elbow (both optional).

Single injection cycle, intramuscular injection into muscles of wrist (mandatory) and shoulder and/or elbow (both optional).

Outcomes

Primary Outcome Measures

Change From Baseline to Week 4 in Maximum Angular Tremor Amplitude of the Wrist (Injected Limb)
No primary efficacy variables are defined for this study. One of the secondary outcome measures is used for CTgov protocol registration and results reporting purposes only. TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum angular tremor amplitude at wrist of the injected limb (unit: degrees). Angular tremor amplitude is the measure of tremor severity. Reduction of angular tremor amplitude at wrist of the injected limb represents tremor improvement.

Secondary Outcome Measures

Change From Baseline to Week 4 in Maximum Log-transformed Accelerometric Tremor Amplitude at Wrist Level (Injected Limb)
TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum log-transformed accelerometric tremor amplitude at wrist level of the injected limb (unit: meter per square second [m/s˄2]). Log-transformed accelerometric tremor amplitude is a measure of tremor severity reflecting the non-vectoral intensity of tremor. Reduction of log-transformed accelerometric tremor amplitude at wrist level of the injected limb represents a tremor improvement.
Change From Baseline to Week 4 in Fahn-Tolosa-Marin (FTM) Tremor Score in Injected Limb (Item 5 [Right Upper Extremity] or 6 [Left Upper Extremity])
The FTM tremor rating scale is used for evaluation of tremor severity and function and consists of three parts (A, B, C). For this outcome measure the score of FTM scale item 5 ("right upper extremity") or item 6 ("left upper extremity") is used (both items are from part A). The outcome values are calculated as the sum of the three functions "at rest", "with posture holding", and "with action and intention". The score for each item ranges from 0 (normal) to 4 (severe), that is, the possible values range from 0 to 12.
Change From Baseline to Week 4 in FTM Motor Performance Score (Items 11-15)
The FTM tremor rating scale was used for evaluation of tremor severity and function. This investigator-assessed scale consists of 3 parts (A, B and C). Part A: Tremor location/Severity rating (items 1-10); Part B: Specific motor tasks / Function rating (items 11-15). Ratings for five motor tasks (handwriting, drawing [large/small spiral, line], and pouring); and Part C: Functional disabilities resulting from tremor/activities of daily living (items 16-23). For this outcome measure, the sum of the five FTM motor performance items (from Part B) were used: item 11 ('handwriting for dominant hand only' - irrespective of its injection or non-injection), items 12 to 15 ('drawing large and small spiral', 'line drawing', 'pouring' for the injected upper limb). The score for each item ranges from 0 (normal) to 4 (severe). Possible values range for total FTM motor performance score: 0-20.
Participant's Global Impression of Change Scale (GICS) at Week 4
The GICS was used to measure the participant'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).
Investigator's Global Impression of Change Scale (GICS) at Week 4
The GICS was used to measure the investigator'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).

Full Information

First Posted
August 1, 2014
Last Updated
February 11, 2021
Sponsor
Merz Pharmaceuticals GmbH
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1. Study Identification

Unique Protocol Identification Number
NCT02207946
Brief Title
Botulinum Toxin A to Treat Arm Tremor
Official Title
Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of NT 201 in the Unilateral Treatment of Essential Tremor of the Upper Limb
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
December 5, 2014 (Actual)
Primary Completion Date
May 9, 2016 (Actual)
Study Completion Date
September 26, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merz Pharmaceuticals GmbH

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The objective of this study is to assess the efficacy and safety of a single, kinematic-analysis-based intramuscular injection of NT 201, compared with placebo, in moderate to marked essential tremor of the upper limb.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Essential Tremor of the Upper Limbs

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
200 Units incobotulinumtoxinA (Xeomin)
Arm Type
Experimental
Arm Description
Single injection cycle, total dose of up to 200 Units, intramuscular injection into muscles of wrist (mandatory) and shoulder and/or elbow (both optional).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Single injection cycle, intramuscular injection into muscles of wrist (mandatory) and shoulder and/or elbow (both optional).
Intervention Type
Drug
Intervention Name(s)
IncobotulinumtoxinA
Other Intervention Name(s)
Xeomin, NT 201, Botulinum toxin type A (150 kiloDalton), free from complexing proteins
Intervention Description
Active ingredient: Clostridium Botulinum neurotoxin Type A free from complexing proteins. Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
Primary Outcome Measure Information:
Title
Change From Baseline to Week 4 in Maximum Angular Tremor Amplitude of the Wrist (Injected Limb)
Description
No primary efficacy variables are defined for this study. One of the secondary outcome measures is used for CTgov protocol registration and results reporting purposes only. TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum angular tremor amplitude at wrist of the injected limb (unit: degrees). Angular tremor amplitude is the measure of tremor severity. Reduction of angular tremor amplitude at wrist of the injected limb represents tremor improvement.
Time Frame
Baseline up to Week 4
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 4 in Maximum Log-transformed Accelerometric Tremor Amplitude at Wrist Level (Injected Limb)
Description
TremorTek is a tremor kinematic analytics investigational device which is used to measure maximum log-transformed accelerometric tremor amplitude at wrist level of the injected limb (unit: meter per square second [m/s˄2]). Log-transformed accelerometric tremor amplitude is a measure of tremor severity reflecting the non-vectoral intensity of tremor. Reduction of log-transformed accelerometric tremor amplitude at wrist level of the injected limb represents a tremor improvement.
Time Frame
Baseline up to Week 4
Title
Change From Baseline to Week 4 in Fahn-Tolosa-Marin (FTM) Tremor Score in Injected Limb (Item 5 [Right Upper Extremity] or 6 [Left Upper Extremity])
Description
The FTM tremor rating scale is used for evaluation of tremor severity and function and consists of three parts (A, B, C). For this outcome measure the score of FTM scale item 5 ("right upper extremity") or item 6 ("left upper extremity") is used (both items are from part A). The outcome values are calculated as the sum of the three functions "at rest", "with posture holding", and "with action and intention". The score for each item ranges from 0 (normal) to 4 (severe), that is, the possible values range from 0 to 12.
Time Frame
Baseline up to Week 4
Title
Change From Baseline to Week 4 in FTM Motor Performance Score (Items 11-15)
Description
The FTM tremor rating scale was used for evaluation of tremor severity and function. This investigator-assessed scale consists of 3 parts (A, B and C). Part A: Tremor location/Severity rating (items 1-10); Part B: Specific motor tasks / Function rating (items 11-15). Ratings for five motor tasks (handwriting, drawing [large/small spiral, line], and pouring); and Part C: Functional disabilities resulting from tremor/activities of daily living (items 16-23). For this outcome measure, the sum of the five FTM motor performance items (from Part B) were used: item 11 ('handwriting for dominant hand only' - irrespective of its injection or non-injection), items 12 to 15 ('drawing large and small spiral', 'line drawing', 'pouring' for the injected upper limb). The score for each item ranges from 0 (normal) to 4 (severe). Possible values range for total FTM motor performance score: 0-20.
Time Frame
Baseline up to Week 4
Title
Participant's Global Impression of Change Scale (GICS) at Week 4
Description
The GICS was used to measure the participant'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).
Time Frame
Week 4
Title
Investigator's Global Impression of Change Scale (GICS) at Week 4
Description
The GICS was used to measure the investigator'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).
Time Frame
Week 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Main Inclusion Criteria: Diagnosis of 'definite essential tremor' in accordance with modified TRIG criteria, as follows: Bilateral postural tremor with or without kinetic tremor, involving hands and forearms, that is visible and persistent. It is to be noted that: Tremor of other body parts may be present in addition to upper limb tremor. Bilateral tremor may be asymmetric. Tremor is reported by patient to be persistent, although the amplitude may fluctuate. First onset of essential tremor at least 6 months before screening with stability of the tremor symptoms over 4 weeks and in the opinion of the investigator definite diagnosis of essential tremor. Moderate-to-marked upper-limb postural and/or kinetic tremor at wrist level, corresponding to Fahn-Tolosa-Marin upper-limb tremor rating of at least 2 categories (scale part C, items 16-23) in the limb to be treated between of 2 or higher. Visible tremor at wrist level in at least one of the four positions/tasks used in kinematic assessments Tremor deemed by the investigator to require a treatment with 30 - 200 U NT 201 for a treatment of up to three joints of the selected upper limb (wrist treatment mandatory). Stable concomitant anti-tremor medication and no clinically relevant findings in routine laboratory examinations. Main Exclusion Criteria: Any neurological signs abnormal for the subject's age, other than the tremor itself and Froment's maneuver. Exposure to the following tremorogenic drugs: Lithium, Valproic acid, Amiodarone, typical and atypical neuroleptics. Exposure to other than the listed tremorogenic or potentially tremorogenic drugs is allowed only if, in the opinion of the investigator, this will not interfere with the study drug evaluation. In these cases, a stable medication should be reached 4 weeks before screening and intended for the time during the study drug evaluation. Trauma to the central nervous system or the nerves of the target limb within the three months preceding the onset of tremor. Evidence of psychogenic origins of tremor. Life habits (e.g. smoking, alcohol or substance abuse) prejudicial to study participation. Prior surgery to treat tremor Recent (16 weeks) treatment with any Botulinum toxin product for any reason. Relevant recent or planned surgery or other specified relevant treatments and/or concomitant disorders.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Merz Medical Expert
Organizational Affiliation
Merz Pharmaceuticals GmbH
Official's Role
Study Director
Facility Information:
Facility Name
Merz Investigational Site #0010191
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Merz Investigational Site #0010317
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3J2H7
Country
Canada
Facility Name
Merz Investigational Site #0010089
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3P 1M3
Country
Canada
Facility Name
Merz Investigational Site #0010078
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
Facility Name
Merz Investigational Site #0010305/1
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6M 2J5
Country
Canada
Facility Name
Merz Investigational Site #0010305/2
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M6M 2J5
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33419261
Citation
Jog M, Lee J, Scheschonka A, Chen R, Ismail F, Boulias C, Hobson D, King D, Althaus M, Simon O, Dersch H, Frucht S, Simpson DM. Tolerability and Efficacy of Customized IncobotulinumtoxinA Injections for Essential Tremor: A Randomized, Double-Blind, Placebo-Controlled Study. Toxins (Basel). 2020 Dec 20;12(12):807. doi: 10.3390/toxins12120807.
Results Reference
result

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Botulinum Toxin A to Treat Arm Tremor

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