Essential Tremor of the Upper Limb
Conditions
Brief summary
The purpose of this study is to determine whether a single treatment with NT 201 (botulinum toxin) is superior to placebo (no medicine) for one-sided treatment of essential tremor in the motor-dominant arm (Unilateral Period). Participants will be assigned to the treatment groups by chance and neither the participants nor the research staff who interact with them will know the allocation. The following treatment cycle will investigate the safety and tolerability of two-sided treatment with NT 201 (botulinum toxin) (Open Label Bilateral Period). All participants will receive NT 201 treatment.
Interventions
DRUGNT 201
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).
DRUGPlacebo
Solution for injection prepared by reconstitution of powder with 0.9% Sodium Chloride (NaCl).
Sponsors
Merz Pharmaceuticals GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- Score of ≥ 2 (at least 1 cm tremor amplitude) in at least two out of three maneuvers of test item 4 (upper limb tremor) of the TETRAS performances scale confirmed by an independent TETRAS expert by means of video assessment.
Exclusion criteria
* History or presence of day-to-day fluctuations in ET which would jeopardize meaningful tremor assessment over time, e.g. severe tremor on one day and minimal or no tremor on another day. * Other neurological signs, such as dystonia, ataxia, or parkinsonism, which in the judgment of the investigator could interfere with the ET diagnosis and/or assessment of ET in ULs. * Tremor types other than ET
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Unilateral Treatment Period: Change From Baseline to Week 6 in Maximum Tremor Amplitude of the Wrist | Baseline up to Week 6 | TremorTek kinematic analytic investigational device is combination of computer software and wearable movement sensors that allows to collect motion data when placed on individual's arm to quantify tremor in various muscle groups that impact shoulder, elbow, wrist. This assessment system was used to measure maximum angular tremor amplitude at wrist of injected limb (unit: degrees). Angular tremor amplitude was measure of tremor severity. Reduction of maximum angular tremor amplitude at wrist of injected limb represented tremor improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Unilateral Treatment Period: Change From Baseline to Week 6 in the Essential Tremor Rating Assessment Scale (TETRAS) Performance Dominant Upper Limb (UL) Score as Assessed by Investigator | Baseline up to Week 6 | The TETRAS was a validated clinical scale for the assessment of essential tremor severity. The TETRAS performance subscale was utilized by the qualified investigators to assess the tremor severity. The TETRAS Performance dominant UL score included TETRAS Performance items 4 (including subitems a, b, c for 3 manoeuvres), 6 to 8 of dominant UL. Each individual item score ranged from 0 to 4. The performance dominant UL score ranged from 0 to 24. Higher scores indicated more severe tremor. |
| Unilateral Treatment Period: Change From Baseline to Week 6 in the TETRAS Activities of Daily Living (ADL) UL Score | Baseline up to Week 6 | TETRAS ADL subscale was another component of TETRAS. ADL subscale of TETRAS was completed by study subjects through an interview procedure to assess impact of tremor on activities of daily living. TETRAS ADL UL score was the sum of eight ADL items (on UL tremor \[items 2-9\]). Items were rated on a 5-point response scale each ranged from 0 (normal status/impact) to 4 (severe status/impact). The ADL UL score ranged from 0 to 32. Higher scores indicated greater tremor severity. |
| Unilateral Treatment Period: Change From Baseline to Week 6 in TETRAS ADL Functional Impact Score | Baseline up to Week 6 | TETRAS ADL Functional Impact score was the sum of the following three ADL items: occupational impairment (item 10), overall disability (item 11), and social impact (item 12) of ET. The items are rated on a 5-point response scale each ranged from 0 (normal status/impact) to 4 (severe status/impact). The ADL Functional Impact score ranged from 0 to 12. Higher scores indicated greater tremor severity. |
| Unilateral Treatment Period: Subject's Global Impression of Change Scale (GICS) Score of Motor-dominant UL at Week 6 | Week 6 | The GICS was used to evaluate overall clinical impression of change after treatment by the subject. The response option was a common 9-point Likert scale ranged from -4 to +4, with the following values: +4 (very much improved); +3 (much improved); +2 (improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (worse); -3 (much worse); -4 (very much worse). A higher score indicated improvements. |
| Unilateral Treatment Period: Investigator's GICS Score of Motor-dominant UL at Week 6 | Week 6 | The GICS was used to evaluate the overall clinical impression of change after treatment by the investigator. The response option was a common 9-point Likert scale ranged from -4 to +4, with the following values: +4 (very much improved); +3 (much improved); +2 (improved); +1 (minimally improved); 0 (no change); -1 (minimally worse); -2 (worse); -3 (much worse); -4 (very much worse). A higher score indicated improvements. |
| Bilateral Treatment Period: Change From Cycle 2 Baseline to Week 6 in TETRAS Performance Dominant UL Score | Baseline of Cycle 2 up to Week 6 (Cycle length = 12 weeks) | TETRAS was a validated clinical scale for the assessment of essential tremor severity. The TETRAS performance subscale was utilized by the qualified investigators to assess the tremor severity. The TETRAS Performance dominant UL score included TETRAS Performance items 4 ((including subitems a, b, c for 3 manoeuvres), 6 to 8 of dominant UL. Each individual item score ranged from 0 to 4. The performance dominant UL score ranged from 0 to 24. Higher scores indicated more severe tremor. |
| Bilateral Treatment Period: Change From Cycle 2 Baseline to Week 6 in TETRAS Performance Subscale Score | Baseline of Cycle 2 up to Week 6 (Cycle length =12 weeks) | The TETRAS was a validated clinical scale for the assessment of essential tremor severity. The TETRAS performance subscale was utilized by the qualified investigators to assess the tremor severity. TETRAS performance subscale consisted of 9 items: head, face, and voice tremor (items 1-3), UL tremor of right and left UL (item 4) in three tasks (forward outstretched postural tremor, lateral "wing-beating" postural tremor, kinetic tremor), Archimedes spirals with both hands, handwriting with motor-dominant hand, and dot approximation task with both hands (items 6-8), and lower limb tremor and standing tremor (items 5 and 9). Each item was rated from 0 (no tremor) to 4 (severe tremor) with overall performance score of 0 to 64, calculated as the sum of subscale items. Higher scores indicated greater tremor severity. |
| Bilateral Treatment Period: Change From Cycle 2 Baseline to Week 6 in TETRAS ADL UL Score | Baseline of Cycle 2 up to Week 6 (Cycle length = 12 weeks) | TETRAS ADL subscale was another component of TETRAS. ADL subscale of TETRAS was completed by study subjects through an interview procedure to assess impact of tremor on activities of daily living. TETRAS ADL UL score was the sum of eight ADL items on UL tremor (items 2-9). Items were rated on a 5-point response scale each ranged from 0 (normal status/impact) to 4 (severe status/impact). The ADL UL score ranged from 0 to 32. Higher scores indicated greater tremor severity. |
| Bilateral Treatment Period: Change From Cycle 2 Baseline to Week 6 in TETRAS ADL Functional Impact Score | Baseline of Cycle 2 up to Week 6 (Cycle length = 12 weeks) | TETRAS ADL Functional Impact score was the sum of the following three ADL items: occupational impairment (item 10), overall disability (item 11), and social impact (item 12) of ET. The items are rated on a 5-point response scale each ranged from 0 (normal status/impact) to 4 (severe status/impact). The ADL Functional Impact score ranged from 0 to 12. Higher scores indicated greater tremor severity. |
| Percentage of Subjects With At-least One Treatment Related Treatment-emergent Adverse Events (TEAEs) | Unilateral Treatment Period: From first injection in unilateral treatment period up to re-injection in Bilateral Treatment Period (Week 24); Bilateral Treatment Period: From re-injection in Bilateral Treatment Period at Week 24 up to end of study(Week 36) | An adverse event (AE) is any untoward medical occurrence in subject administered pharmaceutical product. TEAEs of unilateral treatment period (Cycle 1) = AEs from first injection up to injection in the bilateral treatment period (Week 24). TEAEs of bilateral treatment period (Cycle 2) = AEs from injection in bilateral treatment period up to end of study (Week 36). |
Countries
Canada, Poland, United States
Contacts
STUDY_DIRECTORMerz Medical Expert
Merz Pharmaceuticals GmbH
Participant flow
Recruitment details
Subjects were recruited at 14 investigational sites in the United States, Poland and Canada.
Pre-assignment details
A total of 114 subjects were screened, out of which 78 subjects were randomized, and 77 subjects were treated in this study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized 18-64 years | 29 Participants |
| Age, Customized 65-84 years | 47 Participants |
| Age, Customized >= 85 years | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 75 Participants |
| Sex: Female, Male Female | 37 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 27 | 0 / 72 |
| other Total, other adverse events | 29 / 50 | 5 / 27 | 29 / 72 |
| serious Total, serious adverse events | 3 / 50 | 2 / 27 | 2 / 72 |
Outcome results
None listed