Trial Outcomes & Findings for Open-Label Non-Inferiority Study Evaluating the Efficacy and Safety of Xeomin® in Subjects With Cervical Dystonia Flex (NCT NCT01486264)

Last Updated: 2022-10-27

Results Overview

The validated assessment scale TWSTRS was used to measure the impact of cervical dystonia (CD) on participants. A blinded rater performed all TWSTRS-Severity subscale assessments for a given participant. TWSTRS-Severity subscale score ranges from 0 (=absence of severity) to 35 points (=maximum severity).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

283 participants

Primary outcome timeframe

Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Results posted on

2022-10-27

Participant Flow

The study was conducted at 43 sites in the United States.

A total of 283 participants were screened and randomized in the study. Of these, 282 participants were treated and 207 participants completed the study.

Participant milestones

Participant milestones
Measure	Xeomin Short Flex Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Overall Study STARTED	142	141
Overall Study Treated	142	140
Overall Study COMPLETED	113	94
Overall Study NOT COMPLETED	29	47

Reasons for withdrawal

Reasons for withdrawal
Measure	Xeomin Short Flex Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Overall Study Death	1	1
Overall Study Adverse Event	3	3
Overall Study Lack of Efficacy	6	10
Overall Study Withdrawal by Subject	7	18
Overall Study Physician Decision	1	1
Overall Study Protocol Violation	3	0
Overall Study Lost to Follow-up	3	2
Overall Study Other	5	11
Overall Study Not treated	0	1

Baseline Characteristics

Open-Label Non-Inferiority Study Evaluating the Efficacy and Safety of Xeomin® in Subjects With Cervical Dystonia Flex

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Xeomin Short Flex n=142 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=140 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.	Total n=282 Participants Total of all reporting groups
Age, Continuous	57.4 years STANDARD_DEVIATION 10.62 • n=93 Participants	56.7 years STANDARD_DEVIATION 11.30 • n=4 Participants	57.1 years STANDARD_DEVIATION 10.95 • n=27 Participants
Sex: Female, Male Female	106 Participants n=93 Participants	98 Participants n=4 Participants	204 Participants n=27 Participants
Sex: Female, Male Male	36 Participants n=93 Participants	42 Participants n=4 Participants	78 Participants n=27 Participants
Race/Ethnicity, Customized Hispanic or Latino	6 Participants n=93 Participants	6 Participants n=4 Participants	12 Participants n=27 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	136 Participants n=93 Participants	134 Participants n=4 Participants	270 Participants n=27 Participants
Race/Ethnicity, Customized White	130 Participants n=93 Participants	128 Participants n=4 Participants	258 Participants n=27 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=93 Participants	7 Participants n=4 Participants	14 Participants n=27 Participants
Race/Ethnicity, Customized Asian	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Other	2 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants
Region of Enrollment United States	142 Participants n=93 Participants	140 Participants n=4 Participants	282 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: The per protocol set (PPS) included all participants in the full analysis set (FAS) who was responsive to unilateral brow injection (UBI) at the 4-week control visit after initial injection or had no major protocol deviations.

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=101 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=79 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Baseline in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Severity Subscale Score Based on Blinded Rater Assessment at Week 4 After the 8th Injection	-4.1 score on a scale Standard Deviation 5.5	-2.4 score on a scale Standard Deviation 5.4

SECONDARY outcome

Timeframe: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: FAS was subset of SES participants who were randomly assigned and received at least one injection and for whom TWSTR-Severity value by a blinded rater was available at baseline injection visit and control visit 4 weeks after the 8th injection. Participants who were evaluable for this measure at a given time point were included for this assessment.

The validated assessment scale TWSTRS was used to measure the impact of CD on participants. The scale comprised of 3 subscales: Severity, Disability, and Pain, each of which was scored independently. A blinded rater performed all TWSTRS assessments for a given participant. TWSTRS-Severity subscale score ranges from 0 (=absence of severity) to 35 points (=maximum severity); TWSTRS-Disability subscale score ranges from 0 (no disability) to 30 (maximum disability); and TWSTRS-Pain subscale score ranges from 0 (no pain) to 20 (maximum pain). The total of these 3 comprises the TWSTRS total score which is scored from 0 (no symptoms) to 85 (worst symptoms). Higher scores indicate a greater impact of CD on participant.

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=101 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=79 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Baseline in TWSTRS Total Score Based on Blinded Rater Assessment at Week 4 After the 8th Injection	-8.5 score on a scale Standard Deviation 10.3	-7.6 score on a scale Standard Deviation 11.0

SECONDARY outcome

Timeframe: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

The validated assessment scale TWSTRS was used to measure the impact of CD on participant. The scale comprised of 3 subscales: Severity, Disability, and Pain, each of which was scored independently. An unblinded rater performed all TWSTRS assessments for a given participant. TWSTRS-Severity subscale score ranges from 0 (=absence of severity) to 35 points (=maximum severity); TWSTRS-Disability subscale score ranges from 0 (no disability) to 30 (maximum disability); and TWSTRS-Pain subscale score ranges from 0 (no pain) to 20 (maximum pain). The total of these 3 comprises the TWSTRS total score which is scored from 0 (least symptoms) to 85 (worst symptoms). Higher scores indicate a greater impact of CD on participant.

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=101 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=79 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Baseline in TWSTRS Total Score Based on Unblinded Rater Assessment at Week 4 After the 8th Injection	-9.4 score on a scale Standard Deviation 11.1	-10.3 score on a scale Standard Deviation 10.9

SECONDARY outcome

Timeframe: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

The validated assessment scale TWSTRS was used to measure the impact of cervical dystonia (CD) on participants. An unblinded rater performed all TWSTRS-Severity subscale assessments for a given participant. TWSTRS-Severity score ranges from 0 (absence of severity) to 35 (maximum severity).

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=101 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=79 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Baseline in TWSTRS Severity Subscale Based on Unblinded Rater Assessment at Week 4 After the 8th Injection	-4.8 score on a scale Standard Deviation 6.2	-5.1 score on a scale Standard Deviation 4.9

SECONDARY outcome

Timeframe: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: The FAS was the subset of the SES participants who were randomly assigned and received at least one injection and for whom a TWSTR-Severity value by a blinded rater (primary variable) was available at the baseline injection visit and the control visit 4 weeks after the 8th injection.

The validated assessment scale TWSTRS was used to measure the impact of CD on participant. An unblinded rater performed all TWSTRS-Disability subscale assessments for a given participant. TWSTRS-Disability score ranges from 0 (no disability) to 30 (maximum disability).

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=108 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=90 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Baseline in TWSTRS Disability Subscale Based on Unblinded Rater Assessment at Week 4 After the 8th Injection	-1.9 score on a scale Standard Deviation 4.5	-2.1 score on a scale Standard Deviation 5.8

SECONDARY outcome

Timeframe: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

The validated assessment scale TWSTRS was used to measure the impact of CD on participants. An unblinded rater performed all TWSTRS-Pain subscale assessments for a given participant. TWSTRS-Pain score ranges from 0 (no pain) to 20 (maximum pain).

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=108 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=90 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Baseline in TWSTRS Pain Subscale Based on Unblinded Rater Assessment at Week 4 After the 8th Injection	-2.7 score on a scale Standard Deviation 4.2	-3.1 score on a scale Standard Deviation 4.9

SECONDARY outcome

Timeframe: Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

The Investigator-Rated Global Response assessment for each Xeomin treatment was scored using a 9-point scale with a score ranging from -4 to +4 as follows: -4 (very marked worsening); -3 (marked worsening); -2 (moderately worsening); 1 (minimally worsening); 0 (no change); +1 (minimally improved); +2 (moderately improved); +3 (significantly improved); +4 (complete abolishment of signs and symptoms).

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=104 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=90 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Control Visit Week 4 After First Injection in Investigator-Rated Global Response at Week 4 After the 8th Injection	-0.3 score on a scale Standard Deviation 1.47	-0.1 score on a scale Standard Deviation 1.45

SECONDARY outcome

Timeframe: Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

The Subject-Rated Global Response assessment for each Xeomin treatment was scored using a 9-point scale with a score ranging from -4 to +4 as follows: -4 (very marked worsening); -3 (marked worsening); -2 (moderately worsening); 1 (minimally worsening); 0 (no change); +1 (minimally improved); +2 (moderately improved); +3 (significantly improved); +4 (complete abolishment of signs and symptoms).

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=103 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=90 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Control Visit Week 4 After First Injection in Subject-Rated Global Response at Week 4 After the 8th Injection	0.4 score on a scale Standard Error 1.61	0.5 score on a scale Standard Error 1.79

SECONDARY outcome

Timeframe: Week 4 and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

The Subject Satisfaction assessment for each Xeomin treatment was scored using a 10-point scale to answer the question, "How satisfied are you at the moment with your current therapy? Score ranges from: 1 (completely satisfied) to 10 (completely unsatisfied).

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=94 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=89 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Control Visit Week 4 After First Injection in Subject Satisfaction Score at Week 4 After the 8th Injection	-1.2 score on a scale Standard Deviation 3.42	-0.6 score on a scale Standard Deviation 3.42

SECONDARY outcome

Timeframe: Baseline and 8th injection (Week 44 for Short Flex and Week 84 for Long Flex)

Assessment of Clinical Global Impression Severity was scored using a 7-point scale for severity of illness, in response to the question, "Considering your total clinical experience with this particular population, how ill is the participant at this time?" With scores as: 0 (not assessed); 1 (normal, not ill at all); 2 (borderline ill); 3 (mildly ill); 4 (moderately ill); 5 (markedly ill); 6 (severely ill); and 7 (among the most extremely ill participants).

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=107 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=90 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Baseline in Clinical Global Impression-Severity	-0.5 score on a scale Standard Deviation 0.89	-0.1 score on a scale Standard Deviation 1.03

SECONDARY outcome

Timeframe: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

The CDIP-58 assesses the health impact of CD. The CDIP-58 is composed of eight domains: head and neck (6 items; 6 to 30 points), pain and discomfort (5 items; 5 to 25 points), upper limb activities (9 items; 9 to 45 points), walking (9 items; 9 to 45 points), sleep (4 items; 4 to 20 points), annoyance (8 items; 8 to 40 points), mood (7 items; 7 to 35 points), and psychosocial functioning (10 items; 10 to 50 points). Subscale scores were transformed to a common theoretical range of 0 (no impact) to 100 (most impact). Transformation to a 0 to 100 scale for the sum scores of the sub- and total scales were done using the following formula (all single items have scores from 1 to 5): S0 to 100 =25 \* (\[ SO / NI\] - 1), S0 to 100 = transformed sum score. SO = sum score of the original sub- / total scale. NI = number of items in the sub- / total scale. Negative changes from the baseline total score indicate improvement in the impact of CD on health whereas positive changes indicate worsening.

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=108 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=90 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Baseline in Cervical Dystonia Impact Profile-58 (CDIP-58) Total Score at Week 4 After the 8th Injection	-14.42 score on a scale Standard Deviation 20.377	-12.45 score on a scale Standard Deviation 18.457

SECONDARY outcome

Timeframe: Baseline and Week 4 after the 8th injection (Week 44 to 68 for Short Flex and Week 84 to 104 for Long Flex)

Population: The FAS was the subset of the SES who were randomly assigned and received at least one injection and for whom a TWSTR-Severity value by a blinded rater (primary variable) was available at the baseline injection visit and the control visit 4 weeks after the 8th injection.

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=108 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=90 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Change From Baseline in CDIP-58 Subscales' Scores at Week 4 After the 8th Injection Sleep score	-12.79 score on a scale Standard Deviation 29.045	-9.97 score on a scale Standard Deviation 26.158
Change From Baseline in CDIP-58 Subscales' Scores at Week 4 After the 8th Injection Upper limb activities score	-8.98 score on a scale Standard Deviation 22.822	-8.27 score on a scale Standard Deviation 20.982
Change From Baseline in CDIP-58 Subscales' Scores at Week 4 After the 8th Injection Head and neck score	-22.49 score on a scale Standard Deviation 24.699	-23.70 score on a scale Standard Deviation 27.152
Change From Baseline in CDIP-58 Subscales' Scores at Week 4 After the 8th Injection Pain and discomfort score	-13.79 score on a scale Standard Deviation 27.912	-7.92 score on a scale Standard Deviation 23.906
Change From Baseline in CDIP-58 Subscales' Scores at Week 4 After the 8th Injection Walking score	8.41 score on a scale Standard Deviation 809	-7.01 score on a scale Standard Deviation 20.884
Change From Baseline in CDIP-58 Subscales' Scores at Week 4 After the 8th Injection Annoyance score	15.83 score on a scale Standard Deviation 25.735	-9.69 score on a scale Standard Deviation 24.771
Change From Baseline in CDIP-58 Subscales' Scores at Week 4 After the 8th Injection Mood score	-14.52 score on a scale Standard Deviation 24.307	-10.20 score on a scale Standard Deviation 23.137
Change From Baseline in CDIP-58 Subscales' Scores at Week 4 After the 8th Injection Psychosocial functioning score	-15.90 score on a scale Standard Deviation 24.764	-15.81 score on a scale Standard Deviation 23.428

SECONDARY outcome

Timeframe: Week 4 up to Week 112

The Offset Questionnaire was a single question: "On most days last week, have you noticed that your CD symptoms are better, worse or the same as the week prior? Time to offset of effect was calculated from date of first onset of effect to date of offset of effects.

Outcome measures

Outcome measures
Measure	Xeomin Short Flex n=108 Participants Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=90 Participants Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Time to Offset of Xeomin Effects by Injection Cycle Injection 1	4.8 weeks Standard Deviation 2.85	5.8 weeks Standard Deviation 3.89
Time to Offset of Xeomin Effects by Injection Cycle Injection 2	4.8 weeks Standard Deviation 2.60	6.8 weeks Standard Deviation 3.83
Time to Offset of Xeomin Effects by Injection Cycle Injection 3	5.0 weeks Standard Deviation 2.31	7.8 weeks Standard Deviation 3.52
Time to Offset of Xeomin Effects by Injection Cycle Injection 4	5.1 weeks Standard Deviation 2.60	8.6 weeks Standard Deviation 3.70
Time to Offset of Xeomin Effects by Injection Cycle Injection 5	5.4 weeks Standard Deviation 3.00	9.2 weeks Standard Deviation 3.05
Time to Offset of Xeomin Effects by Injection Cycle Injection 6	6.4 weeks Standard Deviation 2.36	9.5 weeks Standard Deviation 2.50
Time to Offset of Xeomin Effects by Injection Cycle Injection 7	5.4 weeks Standard Deviation 2.63	9.1 weeks Standard Deviation 2.80
Time to Offset of Xeomin Effects by Injection Cycle Injection 8	4.2 weeks Standard Deviation 1.94	—

Adverse Events

Xeomin Short Flex

Serious events: 15 serious events

Other events: 77 other events

Deaths: 1 deaths

Xeomin Long Flex

Serious events: 11 serious events

Other events: 77 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Xeomin Short Flex n=142 participants at risk Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=140 participants at risk Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Gastrointestinal disorders Dysphagia	25.4% 36/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	25.0% 35/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Nervous system disorders Headache	8.5% 12/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	12.1% 17/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Muscular weakness	7.0% 10/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	8.6% 12/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Neck pain	6.3% 9/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	6.4% 9/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Back pain	3.5% 5/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	7.1% 10/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Injury, poisoning and procedural complications Fall	5.6% 8/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	5.0% 7/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Nausea	4.2% 6/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	6.4% 9/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Sinusitis	4.2% 6/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	5.0% 7/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Upper respiratory tract infection	6.3% 9/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	2.9% 4/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Nervous system disorders Dizziness	3.5% 5/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	5.0% 7/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Nasopharyngitis	5.6% 8/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	2.9% 4/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Arthralgia	2.1% 3/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	5.0% 7/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.1% 3/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	5.0% 7/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.

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	Xeomin Short Flex n=142 participants at risk Participants received Xeomin Short Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 6 to 10 weeks interval for up to 762 days.	Xeomin Long Flex n=140 participants at risk Participants received Xeomin Long Flex, intramuscular injection, once on Day 1 (Visit 1) followed by 8 subsequent injection visits at 90 days to 16 weeks interval for up to 875 days.
Infections and infestations Pneumonia	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Gastroenteritis	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Kidney infection	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Sinusitis	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Infections and infestations Urinary tract infection	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Nervous system disorders Syncope	1.4% 2/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Nervous system disorders Burning sensation	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Nervous system disorders Cerebral artery stenosis	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Nervous system disorders Dizziness	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Nervous system disorders Presyncope	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Nervous system disorders Transient ischaemic attack	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Nausea	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	1.4% 2/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Vomiting	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	1.4% 2/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Abdominal distension	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Abdominal pain	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Constipation	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Diarrhoea	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Dysphagia	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Faeces discoloured	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Gastrointestinal disorders Pancreatitis	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Blood and lymphatic system disorders Leukocytosis	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Blood and lymphatic system disorders Microcytic anaemia	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
General disorders Asthenia	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
General disorders Early satiety	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
General disorders Gait disturbance	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Injury, poisoning and procedural complications Ankle fracture	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Injury, poisoning and procedural complications Contusion	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Injury, poisoning and procedural complications Fall	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Injury, poisoning and procedural complications Vascular graft thrombosis	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	1.4% 2/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bronchioloalveolar carcinoma	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer stage III	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Cardiac disorders Bradycardia	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Cardiac disorders Myocardial ischaemia	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Cardiac disorders Sinus arrest	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Cardiac disorders Sinus node dysfunction	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Metabolism and nutrition disorders Dehydration	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Metabolism and nutrition disorders Iron deficiency	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Reproductive system and breast disorders Ovarian cyst	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Vascular disorders Aortic thrombosis	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Vascular disorders Intermittent claudication	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Vascular disorders Peripheral artery stenosis	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Vascular disorders Peripheral ischaemia	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Eye disorders Diplopia	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Hepatobiliary disorders Cholelithiasis	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Immune system disorders Anaphylactic reaction	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Investigations Hepatic enzyme increased	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Investigations Transaminases increased	0.00% 0/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.71% 1/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Psychiatric disorders Completed suicide	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.
Surgical and medical procedures Colon operation	0.70% 1/142 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.	0.00% 0/140 • Baseline up to Day 875 The investigator asked the participant for adverse events (AEs) systematically at each visit.