Trial Outcomes & Findings for Botulinum Toxin A to Treat Arm Tremor (NCT NCT02207946)

NCT ID: NCT02207946

Last Updated: 2021-02-18

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

Baseline up to Week 4

Results posted on

2021-02-18

Participant Flow

The multicenter study was conducted at 6 investigational sites in the United States and Canada.

A total of 52 participants were screened, out of which 30 participants were randomized and treated.

Participant milestones

Participant milestones
Measure	IncobotulinumtoxinA 30 to 200 Units Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 units (U), powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.
Overall Study STARTED	19	11
Overall Study COMPLETED	18	10
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	IncobotulinumtoxinA 30 to 200 Units Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 units (U), powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.
Overall Study Lost to Follow-up	1	0
Overall Study Adverse Event	0	1

Baseline Characteristics

Botulinum Toxin A to Treat Arm Tremor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IncobotulinumtoxinA 30 to 200 U n=19 Participants Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 U, powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo n=11 Participants Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.	Total n=30 Participants Total of all reporting groups
Age, Continuous	68.1 years STANDARD_DEVIATION 10.6 • n=5 Participants	68.2 years STANDARD_DEVIATION 10.2 • n=7 Participants	68.1 years STANDARD_DEVIATION 10.3 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	6 Participants n=7 Participants	15 Participants n=5 Participants
Race/Ethnicity, Customized White	17 Participants n=5 Participants	11 Participants n=7 Participants	28 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Week 4

Population: The full analysis set (FAS) was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 30 to 200 U n=18 Participants Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 units (U), powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo n=11 Participants Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.
Change From Baseline to Week 4 in Maximum Angular Tremor Amplitude of the Wrist (Injected Limb)	-0.47 degree Standard Deviation 0.63	0.07 degree Standard Deviation 0.88

SECONDARY outcome

Timeframe: Baseline up to Week 4

Population: The FAS was defined as the subset of participants who received study medication (incobotulinumtoxinA or placebo) at least once, and for whom a post-baseline value of any efficacy variable was measured.

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.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 30 to 200 U n=18 Participants Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 units (U), powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo n=11 Participants Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.
Change From Baseline to Week 4 in Maximum Log-transformed Accelerometric Tremor Amplitude at Wrist Level (Injected Limb)	-0.73 log[m/s˄2] Standard Deviation 0.63	0.05 log[m/s˄2] Standard Deviation 0.38

SECONDARY outcome

Timeframe: Baseline up to Week 4

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.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 30 to 200 U n=18 Participants Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 units (U), powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo n=11 Participants Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.
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])	-1.9 score on a scale Standard Deviation 1.9	-0.5 score on a scale Standard Deviation 1.8

SECONDARY outcome

Timeframe: Baseline up to Week 4

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.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 30 to 200 U n=18 Participants Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 units (U), powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo n=11 Participants Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.
Change From Baseline to Week 4 in FTM Motor Performance Score (Items 11-15)	-2.8 score on a scale Standard Deviation 1.6	-0.8 score on a scale Standard Deviation 2.0

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 30 to 200 U n=18 Participants Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 units (U), powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo n=11 Participants Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.
Participant's Global Impression of Change Scale (GICS) at Week 4	0.6 score on a scale Standard Deviation 0.6	0.3 score on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 30 to 200 U n=18 Participants Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 units (U), powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo n=11 Participants Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.
Investigator's Global Impression of Change Scale (GICS) at Week 4	0.8 score on a scale Standard Deviation 0.7	0.1 score on a scale Standard Deviation 0.7

Adverse Events

IncobotulinumtoxinA 30 to 200 U

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IncobotulinumtoxinA 30 to 200 U n=19 participants at risk Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 U, powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo n=11 participants at risk Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.
General disorders Influenza like illness	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Chest discomfort	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.

Other adverse events

Additional Information

Public Disclosure Manager

Merz Pharmaceuticals GmbH

Phone: +49 69 1503 1

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Publication of study information usually requires agreement with the sponsor. In case of justified doubts by the sponsor, the INVESTIGATOR will consider these doubts in the publication as long as the scientific neutrality is not affected.
Publication restrictions are in place

Restriction type: OTHER

Measure	IncobotulinumtoxinA 30 to 200 U n=19 participants at risk Participants received incobotulinumtoxinA (also known as NT 201) between 30 to 200 U, powder for solution for injection, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA.	Placebo n=11 participants at risk Participants received placebo solution matched to the volume of incobotulinumtoxinA solution, intramuscular injection, unilaterally into the muscles of the wrist, and optionally, into the elbow and shoulder as based upon kinematic analysis, in a single injection session on Day 1 (Visit 2). The maximum dose per injection site (more than one site per muscle were possible) was 25 U incobotulinumtoxinA placebo.
Infections and infestations Upper respiratory tract infection	10.5% 2/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	18.2% 2/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Cystitis	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Eyelid infection	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Genital infection	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Nail infection	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Sinusitis	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Tooth infection	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Appendicitis	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Muscular weakness	10.5% 2/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Back pain	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Exostosis	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Injury, poisoning and procedural complications Ankle fracture	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Injury, poisoning and procedural complications Head injury	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Injury, poisoning and procedural complications Joint injury	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Injury, poisoning and procedural complications Contusion	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Diarrhoea	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Dry mouth	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Dysphagia	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Eye disorders Glaucoma	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
General disorders Injection site bruising	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
General disorders Injection site pain	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
General disorders Asthenia	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Investigations Blood cholesterol increased	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Metabolism and nutrition disorders Diabetes mellitus	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Respiratory, thoracic and mediastinal disorders Dysphonia	5.3% 1/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Nervous system disorders Hypoaesthesia	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Nervous system disorders Paraesthesia	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Reproductive system and breast disorders Breast mass	0.00% 0/19 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.	9.1% 1/11 • From screening up to Week 24 The investigator asked the participant for adverse events (AEs) systematically at each visit.