Trial Outcomes & Findings for Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study III (BLESSIII) (NCT NCT03985982)

Last Updated: 2025-06-05

Results Overview

The primary endpoint is the percentage of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 4 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. Thus, the primary endpoint is a composite endpoint comprising investigator and subject assessments of treatment effectiveness. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

410 participants

Primary outcome timeframe

Week 4

Results posted on

2025-06-05

Participant Flow

Of 410 enrolled participants, 355 met inclusion criteria and were randomized to treatment.

Participant milestones

Participant milestones
Measure	Botulinum Toxin A Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles
Double-Blind Phase STARTED	266	89	0
Double-Blind Phase COMPLETED	250	84	0
Double-Blind Phase NOT COMPLETED	16	5	0
Open-Label Phase STARTED	0	0	323
Open-Label Phase COMPLETED	0	0	297
Open-Label Phase NOT COMPLETED	0	0	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Botulinum Toxin A Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles
Double-Blind Phase Lost to Follow-up	4	3	0
Double-Blind Phase Physician Decision	1	0	0
Double-Blind Phase Withdrawal by Subject	9	2	0
Double-Blind Phase COVID-19	1	0	0
Double-Blind Phase Early Termination due to Botox Injection while Participating in the Study	1	0	0
Open-Label Phase Lost to Follow-up	0	0	13
Open-Label Phase Physician Decision	0	0	2
Open-Label Phase Withdrawal by Subject	0	0	11

Baseline Characteristics

Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study III (BLESSIII)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Total n=355 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	233 Participants n=5 Participants	81 Participants n=7 Participants	314 Participants n=5 Participants
Age, Categorical >=65 years	33 Participants n=5 Participants	8 Participants n=7 Participants	41 Participants n=5 Participants
Age, Continuous	52.2 years STANDARD_DEVIATION 11.24 • n=5 Participants	49.4 years STANDARD_DEVIATION 12.36 • n=7 Participants	51.5 years STANDARD_DEVIATION 11.58 • n=5 Participants
Sex: Female, Male Female	248 Participants n=5 Participants	80 Participants n=7 Participants	328 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	9 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	66 Participants n=5 Participants	22 Participants n=7 Participants	88 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	200 Participants n=5 Participants	67 Participants n=7 Participants	267 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	25 Participants n=5 Participants	7 Participants n=7 Participants	32 Participants n=5 Participants
Race (NIH/OMB) White	236 Participants n=5 Participants	79 Participants n=7 Participants	315 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	225 Participants n=5 Participants	79 Participants n=7 Participants	304 Participants n=5 Participants
Region of Enrollment Austria	41 Participants n=5 Participants	10 Participants n=7 Participants	51 Participants n=5 Participants
Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Investigator's In-clinic Assessment · No facial wrinkles	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Investigator's In-clinic Assessment · Mild facial wrinkles	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Investigator's In-clinic Assessment · Moderate facial wrinkles	64 Participants n=5 Participants	22 Participants n=7 Participants	86 Participants n=5 Participants
Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Investigator's In-clinic Assessment · Severe facial wrinkles	202 Participants n=5 Participants	67 Participants n=7 Participants	269 Participants n=5 Participants
Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Subject's In-clinic Assessment · No facial wrinkles	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Subject's In-clinic Assessment · Mild facial wrinkles	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Subject's In-clinic Assessment · Moderate facial wrinkles	70 Participants n=5 Participants	25 Participants n=7 Participants	95 Participants n=5 Participants
Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Subject's In-clinic Assessment · Severe facial wrinkles	196 Participants n=5 Participants	64 Participants n=7 Participants	260 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 4

Population: The population used consists of all randomized subjects, regardless of whether they received study medication. Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale (FWS) at baseline or week 4 were assigned as being non-responders.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at Week 4 Visit Relative to Baseline, Based on Both the Investigators´ and the Subjects´ In-clinic Assessments.	172 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Week 4

Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.

Extent of change in psychological impact at week 4 after first treatment, relative to baseline, assessed by * modified Skindex-16 (Glabellar Line Quality of Life Scale, \[GL-QoL\]): Each of 7 items rated on 5-point scale: 0/Never, 1/Rarely, 2/Sometimes, 3/Often, 4/Always bothered, than rescaled to a 0 to 100 standardized score; Emotional Domain is the mean of 4 of the items; Social Functioning Domain is the mean of 3 of the items; Overall score is the mean of all 7 items. All reported scores ranging from 0 (best outcome) to 100 (worst outcome). * validated FACE-Q Appraisal of Lines Between Eyebrows scale: Each of 7 items rated on 4-point scale: 1/Not at all, 2/a little, 3/moderately, 4/extremely. Reported score is the sum of the 7 items, standardized on a scale from 0 (worst outcome) to 100 (best outcome). * Age Appraisal visual analog scale \[VAS\]: Perception of Age compared to actual age, in years ranging from -15 years (best outcome) to +15 years (worst outcome).

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=264 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=86 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) Modified Skindex-16 (GL-QoL) Emotional domain - Change from Baseline at Week 4	-42.27 score on a scale Standard Deviation 34.484	0.50 score on a scale Standard Deviation 20.427	—	—
Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) Modified Skindex-16 (GL-QoL) Social Functioning domain - Change from Baseline at Week 4	-33.14 score on a scale Standard Deviation 33.193	-2.23 score on a scale Standard Deviation 31.088	—	—
Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) Modified Skindex-16 (GL-QoL) Overall score - Change from Baseline at Week 4	-38.35 score on a scale Standard Deviation 31.075	-0.67 score on a scale Standard Deviation 22.369	—	—
Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) FACE-Q Appraisal of Lines Between Eyebrows - Change from Baseline at Week 4	46.4 score on a scale Standard Deviation 28.62	-2.9 score on a scale Standard Deviation 21.60	—	—
Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) Age Appraisal VAS - Change from Baseline at Week 4	-2.3 score on a scale Standard Deviation 4.20	-0.2 score on a scale Standard Deviation 3.42	—	—

SECONDARY outcome

Timeframe: Week 12

Percentage of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 12 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Percentage of Responders at Maximum Frown at Week 12	56 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Week 16

Population: The population used consists of all randomized subjects for whom data are available for week 16 or who were re-treated before week 16. They were analyzed as randomized and participants who were re-treated before week 16 were counted as non-responders.

Percentage of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 16 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=254 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=84 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Percentage of Responders at Week 16	27 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Week 20

Population: The population used consists of all randomized subjects for whom data are available for week 20 or who were re-treated before week 20. They were analyzed as randomized and participants who were re-treated before week 20 were counted as non-responders.

Percentage of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 20 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=254 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=84 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Percentage of Responders at Week 20	5 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Week 4

Population: The population used consists of all randomized subjects with a Facial Wrinkle Scale (FWS) score at rest \>=1 at baseline. Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale at week 4 were assigned as being non-responders.

The Percentage of subjects with a ≥ 1 point reduction in Facial Wrinkle Scale (FWS) score at rest at week 4 in the first treatment cycle, based separately on the investigators' and the subjects' in-clinic assessments (applicable only for subjects who have a FWS score at rest ≥ 1 at baseline). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest at Week 4 Based Separately on the Investigators´ and the Subjects´ In-clinic Assessments Investigator's In-clinic Assessment	163 Participants	8 Participants	—	—
The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest at Week 4 Based Separately on the Investigators´ and the Subjects´ In-clinic Assessments Subject's In-clinic Assessment	214 Participants	11 Participants	—	—

SECONDARY outcome

Timeframe: Week 1, Week 2 and Week 8

The Percentage of responders among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score at maximum frown of 0 or 1 and an improvement ≥ 2 points in FWS score (at maximum frown) during the first treatment cycle visit relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint, at weeks 1, 2 and 8). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Responder Rate at Weeks 1, 2 and 8 Week 1	150 Participants	0 Participants	—	—
Responder Rate at Weeks 1, 2 and 8 Week 2	189 Participants	0 Participants	—	—
Responder Rate at Weeks 1, 2 and 8 Week 8	129 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Week 2, 4, 12, 16 and 20

Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.

The percentage of subjects with ≥ 2-point and ≥ 1 reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle visit relative to baseline, based on the independent rater's assessment of photographs (at baseline and visits 2, 4, 12, 16 and 20 weeks after treatment, within the first treatment cycle). The median value of all assessments of the same photography was considered for analysis. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) ≥ 2-point reduction - Week 2	150 Participants	0 Participants	—	—
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) ≥ 2-point reduction - Week 4	144 Participants	0 Participants	—	—
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) ≥ 2-point reduction - Week 12	11 Participants	1 Participants	—	—
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) ≥ 2-point reduction - Week 16	4 Participants	0 Participants	—	—
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) ≥ 2-point reduction - Week 20	2 Participants	0 Participants	—	—
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) ≥ 1-point reduction - Week 2	235 Participants	6 Participants	—	—
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) ≥ 1-point reduction - Week 4	234 Participants	9 Participants	—	—
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) ≥ 1-point reduction - Week 12	71 Participants	5 Participants	—	—
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) ≥ 1-point reduction - Week 16	29 Participants	0 Participants	—	—
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) ≥ 1-point reduction - Week 20	21 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: From treatment at Day 0 to Week 4 in Treatment Cycle 1

Population: The population used consists of all randomized subjects. Participants were analyzed as randomized.

Time to onset of effect in the BoNT/A-DP and placebo groups in the first treatment cycle, as measured at weeks 1, 2 and 4 based separately on subject and investigator assessment. Onset of effect defined as at least a 1 point improvement in Facial Wrinkle Scale (FWS) score from baseline (at maximum frown). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Time to Onset of Effect in the BoNT/A-DP and Placebo Groups in the First Treatment Cycle	8 Days Interval 8.0 to 9.0	NA Days The median and inter-quartile range cannot be calculated due to the low number of subjects showing an effect in this arm.	—	—

SECONDARY outcome

Timeframe: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)

Population: The population used consists of all randomized subjects who were treated in the respective study cycle and treatment group. Participants were analyzed as randomized.

The extent of subject perceptions of effect of, and satisfaction with, treatment in the BoNT/A-DP and placebo groups, during each treatment cycle, as assessed by the validated FACE-Q Satisfaction with Outcome Scale. The FACE-Q Satisfaction with Outcome scale is a patient-reported outcome measure designed to assess a patient's satisfaction with the results of a facial aesthetic procedure. This scale comprises six items, each with four response options: "definitely agree," "somewhat agree," "somewhat disagree," and "definitely disagree."

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=323 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - miraculous · Definitely disagree	31 Participants	78 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - miraculous · Somewhat disagree	46 Participants	8 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - miraculous · Somewhat agree	88 Participants	0 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - miraculous · Definitely agree	99 Participants	0 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - miraculous · Missing	2 Participants	3 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - pleased · Definitely disagree	—	—	17 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - pleased · Somewhat disagree	—	—	20 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - pleased · Somewhat agree	—	—	75 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - pleased · Definitely agree	—	—	200 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - pleased · Missing	—	—	11 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - expected · Definitely disagree	—	—	24 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - expected · Somewhat disagree	—	—	34 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - expected · Somewhat agree	—	—	78 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - expected · Definitely agree	—	—	176 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - expected · Missing	—	—	11 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - great · Definitely disagree	—	—	30 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - great · Somewhat disagree	—	—	23 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - great · Somewhat agree	—	—	80 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - great · Definitely agree	—	—	179 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - great · Missing	—	—	11 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - look in the mirror · Definitely disagree	—	—	25 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - look in the mirror · Somewhat disagree	—	—	47 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - look in the mirror · Somewhat agree	—	—	111 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - look in the mirror · Definitely agree	—	—	129 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - look in the mirror · Missing	—	—	11 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - fantastic · Definitely disagree	—	—	36 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - fantastic · Somewhat disagree	—	—	46 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - fantastic · Somewhat agree	—	—	90 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - fantastic · Definitely agree	—	—	140 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - fantastic · Missing	—	—	11 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - miraculous · Definitely disagree	—	—	52 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - miraculous · Somewhat disagree	—	—	53 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - miraculous · Somewhat agree	—	—	105 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - miraculous · Definitely agree	—	—	102 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 2 Week 4 - miraculous · Missing	—	—	11 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - pleased · Definitely disagree	—	—	16 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - pleased · Somewhat disagree	—	—	19 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - pleased · Somewhat agree	—	—	60 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - pleased · Definitely agree	—	—	166 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - pleased · Missing	—	—	4 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - expected · Definitely disagree	—	—	20 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - expected · Somewhat disagree	—	—	23 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - expected · Somewhat agree	—	—	62 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - expected · Definitely agree	—	—	156 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - expected · Missing	—	—	4 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - great · Definitely disagree	—	—	24 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - great · Somewhat disagree	—	—	30 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - great · Somewhat agree	—	—	56 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - great · Definitely agree	—	—	151 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - great · Missing	—	—	4 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - look in the mirror · Definitely disagree	—	—	26 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - look in the mirror · Somewhat disagree	—	—	31 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - look in the mirror · Somewhat agree	—	—	100 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - look in the mirror · Definitely agree	—	—	104 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - look in the mirror · Missing	—	—	4 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - fantastic · Definitely disagree	—	—	35 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - fantastic · Somewhat disagree	—	—	31 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - fantastic · Somewhat agree	—	—	72 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - fantastic · Definitely agree	—	—	123 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - fantastic · Missing	—	—	4 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - miraculous · Definitely disagree	—	—	52 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - miraculous · Somewhat disagree	—	—	34 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - miraculous · Somewhat agree	—	—	77 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - miraculous · Definitely agree	—	—	98 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 3 Week 4 - miraculous · Missing	—	—	4 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - pleased · Definitely disagree	—	—	12 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - pleased · Somewhat disagree	—	—	6 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - pleased · Somewhat agree	—	—	37 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - pleased · Definitely agree	—	—	83 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - pleased · Missing	—	—	1 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - expected · Definitely disagree	—	—	10 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - expected · Somewhat disagree	—	—	17 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - expected · Somewhat agree	—	—	34 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - expected · Definitely agree	—	—	77 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - expected · Missing	—	—	1 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - great · Definitely disagree	—	—	17 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - great · Somewhat disagree	—	—	16 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - great · Somewhat agree	—	—	33 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - great · Definitely agree	—	—	72 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - great · Missing	—	—	1 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - look in the mirror · Definitely disagree	—	—	15 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - look in the mirror · Somewhat disagree	—	—	18 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - look in the mirror · Somewhat agree	—	—	55 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - look in the mirror · Definitely agree	—	—	50 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - look in the mirror · Missing	—	—	1 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - fantastic · Definitely disagree	—	—	21 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - fantastic · Somewhat disagree	—	—	16 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - fantastic · Somewhat agree	—	—	46 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - fantastic · Definitely agree	—	—	55 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - fantastic · Missing	—	—	1 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - miraculous · Definitely disagree	—	—	29 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - miraculous · Somewhat disagree	—	—	23 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - miraculous · Somewhat agree	—	—	45 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - miraculous · Definitely agree	—	—	41 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 4 Week 4 - miraculous · Missing	—	—	1 Participants	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - fantastic · Definitely disagree	25 Participants	78 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - pleased · Definitely disagree	16 Participants	78 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - pleased · Somewhat disagree	13 Participants	3 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - pleased · Somewhat agree	46 Participants	4 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - pleased · Definitely agree	189 Participants	1 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - pleased · Missing	2 Participants	3 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - expected · Definitely disagree	17 Participants	74 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - expected · Somewhat disagree	27 Participants	7 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - expected · Somewhat agree	69 Participants	5 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - expected · Definitely agree	151 Participants	0 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - expected · Missing	2 Participants	3 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - great · Definitely disagree	23 Participants	77 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - great · Somewhat disagree	20 Participants	7 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - great · Somewhat agree	58 Participants	2 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - great · Definitely agree	163 Participants	0 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - great · Missing	2 Participants	3 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - look in the mirror · Definitely disagree	18 Participants	74 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - look in the mirror · Somewhat disagree	34 Participants	10 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - look in the mirror · Somewhat agree	101 Participants	2 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - look in the mirror · Definitely agree	111 Participants	0 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - look in the mirror · Missing	2 Participants	3 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - fantastic · Somewhat disagree	31 Participants	7 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - fantastic · Somewhat agree	74 Participants	1 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - fantastic · Definitely agree	134 Participants	0 Participants	—	—
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. Cycle 1 Week 4 - fantastic · Missing	2 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: Week 2, Week 4, Week 12, Week 16, Week 20 of Treatment Cycle 1

Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.

The percentage of subjects with a ≥ 1 point reduction in Facial Wrinkle Scale (FWS) score at rest in the BoNT/A-DP and placebo groups, relative to baseline, during the first treatment cycle, based on the independent rater's assessment of photos. The median value of all assessments of the same photography was considered for analysis. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. Week 2	106 Participants	9 Participants	—	—
The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. Week 4	100 Participants	13 Participants	—	—
The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. Week 12	37 Participants	8 Participants	—	—
The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. Week 16	21 Participants	0 Participants	—	—
The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. Week 20	11 Participants	1 Participants	—	—

SECONDARY outcome

Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.

The percentage of subjects with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at 4 weeks after re-treatment relative to the rating at the preceding end-of-cycle visit, based on both the investigator's and the subject's in-clinic assessments (composite endpoint). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=323 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at 4 Weeks After Re-treatment Relative to the Rating at the Preceding End-of-Cycle Visit. Week 4 after 1st Re-treatment	153 Participants	—	—	—
Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at 4 Weeks After Re-treatment Relative to the Rating at the Preceding End-of-Cycle Visit. Week 4 after 3rd Re-treatment	43 Participants	—	—	—
Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at 4 Weeks After Re-treatment Relative to the Rating at the Preceding End-of-Cycle Visit. Week 4 after 2nd Re-treatment	119 Participants	—	—	—

SECONDARY outcome

Timeframe: Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 of Treatment Cycle 1

Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.

The percentage of subjects with ≥ 1-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle at week 1, 2, 4, 8, 12, 16 and 20 relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). For week 16 and 20 subjects who were re-treated before the respective visits were counted as non-responders. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline Week 1	220 Participants	2 Participants	—	—
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline Week 2	234 Participants	0 Participants	—	—
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline Week 4	236 Participants	0 Participants	—	—
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline Week 8	213 Participants	1 Participants	—	—
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline Week 12	162 Participants	2 Participants	—	—
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline Week 16	94 Participants	1 Participants	—	—
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline Week 20	46 Participants	0 Participants	—	—

SECONDARY outcome

Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.

The percentage of subjects with ≥ 1-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP during each re-treatment cycle at week 4 relative to re-treatment baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=323 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During Each Re-treatment Cycle at Week 4 Relative to Re-treatment-baseline. Week 4 after 1st Re-treatment	267 Participants	—	—	—
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During Each Re-treatment Cycle at Week 4 Relative to Re-treatment-baseline. Week 4 after 2nd Re-treatment	210 Participants	—	—	—
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During Each Re-treatment Cycle at Week 4 Relative to Re-treatment-baseline. Week 4 after 3rd Re-treatment	104 Participants	—	—	—

SECONDARY outcome

Timeframe: Through study completion (60 weeks)

Population: The population used consists of all subjects who received at least one injection with study medication. Participants were analyzed as treated.

Number of Participants with treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest (AESIs)

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=323 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) Subjects with any Treatment Emergent Adverse Event (TEAE)	48 Participants	14 Participants	80 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) Subjects with any Study Medication Related TEAE	4 Participants	0 Participants	8 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) Subjects with any Injection Procedure Related TEAE	4 Participants	0 Participants	6 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) Subjects with any Severe TEAE	1 Participants	0 Participants	3 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) Subjects with severe study drug related TEAE	0 Participants	0 Participants	0 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) Subjects with severe injection procedure related TEAE	0 Participants	0 Participants	0 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) Subjects with any Serious TEAE	1 Participants	1 Participants	4 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) Subjects with any Adverse Events of Special Interest (AESI)	1 Participants	0 Participants	7 Participants	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) Subjects with any TEAE leading to discontinuation	0 Participants	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Through study completion (60 weeks)

Population: The population used consists of all subjects who received at least one injection with study medication. Participants were analyzed as treated. Confirmation assays have only been performed for subjects with a reactive Screening Assay result.

Number of Participants with Neutralizing Anti-Drug Antibodies Antibody formation, evaluation pre-dose before each treatment, at 4 weeks after each treatment and at the final study visit.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=266 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=323 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Number of Participants With Neutralizing Anti-Drug Antibodies End of Study - ADA Screening Assay - Reactive	0 Participants	0 Participants	21 Participants	—
Number of Participants With Neutralizing Anti-Drug Antibodies End of Study - ADA Confirmation Assay - Confirmed	0 Participants	0 Participants	0 Participants	—
Number of Participants With Neutralizing Anti-Drug Antibodies Baseline - Anti-Drug Antibodies (ADA) Screening Assay - Reactive	23 Participants	4 Participants	—	—
Number of Participants With Neutralizing Anti-Drug Antibodies Baseline - ADA Confirmation Assay - Confirmed	0 Participants	0 Participants	—	—

SECONDARY outcome

Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.

Safety assessments by evaluating change from baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=250 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=82 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=299 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 1 - Basophils (x10^9 cells/L)	0.004 x10^9 cells/L Standard Deviation 0.0413	0.012 x10^9 cells/L Standard Deviation 0.0556	—	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 1 - Eosinophils (x10^9 cells/L)	0.006 x10^9 cells/L Standard Deviation 0.0726	0.007 x10^9 cells/L Standard Deviation 0.0767	—	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 1 - Leukocytes (x10^9 cells/L)	-0.029 x10^9 cells/L Standard Deviation 1.4925	0.227 x10^9 cells/L Standard Deviation 1.4308	—	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 1 - Lymphocytes (x10^9 cells/L)	-0.038 x10^9 cells/L Standard Deviation 0.4554	-0.027 x10^9 cells/L Standard Deviation 0.4222	—	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 1 - Monocytes (x10^9 cells/L)	-0.027 x10^9 cells/L Standard Deviation 0.1607	-0.019 x10^9 cells/L Standard Deviation 0.2154	—	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 1 - Neutrophils (x10^9 cells/L)	0.027 x10^9 cells/L Standard Deviation 1.3211	0.252 x10^9 cells/L Standard Deviation 1.1477	—	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 1 - Platelets (x10^9 cells/L)	0.3 x10^9 cells/L Standard Deviation 37.31	-0.8 x10^9 cells/L Standard Deviation 38.87	—	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 2 - Basophils (x10^9 cells/L)	—	—	-0.002 x10^9 cells/L Standard Deviation 0.0565	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 2 - Lymphocytes (x10^9 cells/L)	—	—	0.043 x10^9 cells/L Standard Deviation 0.4282	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 2 - Monocytes (x10^9 cells/L)	—	—	-0.002 x10^9 cells/L Standard Deviation 0.1123	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 2 - Neutrophils (x10^9 cells/L)	—	—	-0.048 x10^9 cells/L Standard Deviation 1.3470	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 3 - Eosinophils (x10^9 cells/L)	—	—	-0.002 x10^9 cells/L Standard Deviation 0.1059	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 3 - Leukocytes (x10^9 cells/L)	—	—	-0.050 x10^9 cells/L Standard Deviation 2.0753	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 3 - Lymphocytes (x10^9 cells/L)	—	—	0.021 x10^9 cells/L Standard Deviation 0.4473	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 3 - Monocytes (x10^9 cells/L)	—	—	-0.018 x10^9 cells/L Standard Deviation 0.1246	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 3 - Neutrophils (x10^9 cells/L)	—	—	-0.034 x10^9 cells/L Standard Deviation 1.9383	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 3 - Platelets (x10^9 cells/L)	—	—	6.1 x10^9 cells/L Standard Deviation 39.16	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 4 - Basophils (x10^9 cells/L)	—	—	-0.019 x10^9 cells/L Standard Deviation 0.0475	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 4 - Eosinophils (x10^9 cells/L)	—	—	-0.026 x10^9 cells/L Standard Deviation 0.0859	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 4 - Monocytes (x10^9 cells/L)	—	—	-0.025 x10^9 cells/L Standard Deviation 0.1698	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 4 - Neutrophils (x10^9 cells/L)	—	—	-0.344 x10^9 cells/L Standard Deviation 1.3644	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 4 - Platelets (x10^9 cells/L)	—	—	0.4 x10^9 cells/L Standard Deviation 41.64	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 2 - Eosinophils (x10^9 cells/L)	—	—	0.009 x10^9 cells/L Standard Deviation 0.0998	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 2 - Leukocytes (x10^9 cells/L)	—	—	0.000 x10^9 cells/L Standard Deviation 1.5182	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 2 - Platelets (x10^9 cells/L)	—	—	6.1 x10^9 cells/L Standard Deviation 37.89	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 3 - Basophils (x10^9 cells/L)	—	—	-0.018 x10^9 cells/L Standard Deviation 0.0496	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 4 - Leukocytes (x10^9 cells/L)	—	—	-0.404 x10^9 cells/L Standard Deviation 1.5800	—
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Week 4 of cycle 4 - Lymphocytes (x10^9 cells/L)	—	—	0.003 x10^9 cells/L Standard Deviation 0.4665	—

SECONDARY outcome

Safety assessments by evaluating change from baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=259 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=84 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=301 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 1 - Alanine Aminotransferase (U/L)	-0.1 U/L Standard Deviation 9.32	1.9 U/L Standard Deviation 19.35	—	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 1 - Alkaline phosphatase (U/L)	-0.8 U/L Standard Deviation 10.99	-0.5 U/L Standard Deviation 12.30	—	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 1 - Aspartate Aminotransferase (U/L)	0.2 U/L Standard Deviation 11.28	0.1 U/L Standard Deviation 8.63	—	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 2 - Alanine Aminotransferase (U/L)	—	—	1.1 U/L Standard Deviation 10.68	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 2 - Alkaline phosphatase (U/L)	—	—	0.9 U/L Standard Deviation 9.42	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 2 - Aspartate Aminotransferase (U/L)	—	—	-0.2 U/L Standard Deviation 12.76	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 2 - Gamma Glutamyl Transpeptidase (U/L)	—	—	1.3 U/L Standard Deviation 11.09	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 3 - Alanine Aminotransferase (U/L)	—	—	-0.4 U/L Standard Deviation 13.43	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 3 - Alkaline phosphatase (U/L)	—	—	0.6 U/L Standard Deviation 10.89	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 3 - Aspartate Aminotransferase (U/L)	—	—	-1.0 U/L Standard Deviation 14.73	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 3 - Gamma Glutamyl Transpeptidase (U/L)	—	—	0.0 U/L Standard Deviation 9.64	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 4 - Alanine Aminotransferase (U/L)	—	—	-0.2 U/L Standard Deviation 10.82	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 4 - Alkaline phosphatase (U/L)	—	—	0.9 U/L Standard Deviation 10.75	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 4 - Aspartate Aminotransferase (U/L)	—	—	-1.6 U/L Standard Deviation 14.54	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 1 - Gamma Glutamyl Transpeptidase (U/L)	0.8 U/L Standard Deviation 50.89	0.8 U/L Standard Deviation 12.41	—	—
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase Week 4 of cycle 4 - Gamma Glutamyl Transpeptidase (U/L)	—	—	1.0 U/L Standard Deviation 9.59	—

SECONDARY outcome

Safety assessments by evaluating change from baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=259 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=84 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=301 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 1 - Potassium (mmol/L)	-0.06 mmol/L Standard Deviation 0.405	-0.09 mmol/L Standard Deviation 0.431	—	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 1 - Sodium (mmol/L)	-0.1 mmol/L Standard Deviation 2.39	-0.3 mmol/L Standard Deviation 2.35	—	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 1 - Urea nitrogen (mmol/L)	0.01 mmol/L Standard Deviation 1.356	0.00 mmol/L Standard Deviation 1.123	—	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of cycle 2 - Cholesterol (mmol/L)	—	—	0.07 mmol/L Standard Deviation 0.5910	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 2 - Glucose (mmol/L)	—	—	0.086 mmol/L Standard Deviation 1.2927	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 2 - Potassium (mmol/L)	—	—	0.03 mmol/L Standard Deviation 0.391	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 2 - Sodium (mmol/L)	—	—	-0.1 mmol/L Standard Deviation 2.28	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 2 - Urea nitrogen (mmol/L)	—	—	-0.05 mmol/L Standard Deviation 1.277	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of cycle 3 - Cholesterol (mmol/L)	—	—	0.021 mmol/L Standard Deviation 0.7421	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 3 - Urea nitrogen (mmol/L)	—	—	0.01 mmol/L Standard Deviation 1.272	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 4 - Cholesterol (mmol/L)	—	—	0.040 mmol/L Standard Deviation 0.6614	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 4 - Glucose (mmol/L)	—	—	-0.098 mmol/L Standard Deviation 1.9131	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 4 - Potassium (mmol/L)	—	—	0.08 mmol/L Standard Deviation 0.039	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 4 - Sodium (mmol/L)	—	—	0.2 mmol/L Standard Deviation 1.87	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 4 - Urea nitrogen (mmol/L)	—	—	0.06 mmol/L Standard Deviation 1.398	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of cycle 1 - Cholesterol (mmol/L)	-0.119 mmol/L Standard Deviation 0.6477	-0.049 mmol/L Standard Deviation 0.5400	—	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 1 - Glucose (mmol/L)	0.317 mmol/L Standard Deviation 1.1751	0.290 mmol/L Standard Deviation 0.9429	—	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 3 - Glucose (mmol/L)	—	—	0.185 mmol/L Standard Deviation 1.5644	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 3 - Potassium (mmol/L)	—	—	0.03 mmol/L Standard Deviation 0.415	—
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen Week 4 of of cycle 3 - Sodium (mmol/L)	—	—	0.1 mmol/L Standard Deviation 2.44	—

SECONDARY outcome

Safety assessments by evaluating change from baseline of Bilirubin, Creatinin as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=259 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=84 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=301 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Change From to Baseline of Bilirubin, Creatinin Week 4 of cycle 1 - Bilirubin (μmol/L)	0.05 μmol/L Standard Deviation 3.555	-0.14 μmol/L Standard Deviation 3.597	—	—
Change From to Baseline of Bilirubin, Creatinin Week 4 of cycle 1 - Creatinine (μmol/L)	0.52 μmol/L Standard Deviation 8.404	-0.30 μmol/L Standard Deviation 6.556	—	—
Change From to Baseline of Bilirubin, Creatinin Week 4 of cycle 2 - Bilirubin (μmol/L)	—	—	-0.12 μmol/L Standard Deviation 3.329	—
Change From to Baseline of Bilirubin, Creatinin Week 4 of cycle 2 - Creatinine (μmol/L)	—	—	-0.49 μmol/L Standard Deviation 8.550	—
Change From to Baseline of Bilirubin, Creatinin Week 4 of cycle 3 - Bilirubin (μmol/L)	—	—	-0.14 μmol/L Standard Deviation 3.283	—
Change From to Baseline of Bilirubin, Creatinin Week 4 of cycle 3 - Creatinine (μmol/L)	—	—	0.06 μmol/L Standard Deviation 9.553	—
Change From to Baseline of Bilirubin, Creatinin Week 4 of cycle 4 - Bilirubin (μmol/L)	—	—	0.52 μmol/L Standard Deviation 3.203	—
Change From to Baseline of Bilirubin, Creatinin Week 4 of cycle 4 - Creatinine (μmol/L)	—	—	-0.66 μmol/L Standard Deviation 9.536	—

SECONDARY outcome

Safety assessments by evaluating change from baseline of Erythrocytes as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=250 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=82 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=299 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Change From Baseline of Erythrocytes Cycle 1	-0.002 x10^12 cells/L Standard Deviation 0.2425	-0.038 x10^12 cells/L Standard Deviation 0.2194	—	—
Change From Baseline of Erythrocytes Cycle 2	—	—	0.032 x10^12 cells/L Standard Deviation 0.2091	—
Change From Baseline of Erythrocytes Cycle 3	—	—	0.063 x10^12 cells/L Standard Deviation 0.2619	—
Change From Baseline of Erythrocytes Cycle 4	—	—	0.041 x10^12 cells/L Standard Deviation 0.2716	—

SECONDARY outcome

Safety assessments by evaluating change from baseline of Erythrocytes MCV as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=250 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=82 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=299 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Change From Baseline of Erythrocytes MCV Cycle 1	-0.78 fL Standard Deviation 2.615	-0.79 fL Standard Deviation 2.860	—	—
Change From Baseline of Erythrocytes MCV Cycle 2	—	—	-0.38 fL Standard Deviation 3.070	—
Change From Baseline of Erythrocytes MCV Cycle 3	—	—	0.53 fL Standard Deviation 4.209	—
Change From Baseline of Erythrocytes MCV Cycle 4	—	—	2.18 fL Standard Deviation 3.875	—

SECONDARY outcome

Safety assessments by evaluating change from baseline of Erythrocyte MCHC, Hemoglobin as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=250 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=82 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=299 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Change From Baseline of Erythrocyte MCHC, Hemoglobin Week 4 of cycle 1 - Erythrocyte MCHC (g/dL)	0.32 g/dL Standard Deviation 0.954	0.33 g/dL Standard Deviation 1.041	—	—
Change From Baseline of Erythrocyte MCHC, Hemoglobin Week 4 of cycle 2 - Hemoglobin (g/dL)	—	—	0.12 g/dL Standard Deviation 0.638	—
Change From Baseline of Erythrocyte MCHC, Hemoglobin Week 4 of cycle 3 - Erythrocyte MCHC (g/dL)	—	—	-0.12 g/dL Standard Deviation 1.366	—
Change From Baseline of Erythrocyte MCHC, Hemoglobin Week 4 of cycle 3 - Hemoglobin (g/dL)	—	—	-0.21 g/dL Standard Deviation 0.821	—
Change From Baseline of Erythrocyte MCHC, Hemoglobin Week 4 of cycle 4 - Erythrocyte MCHC (g/dL)	—	—	-0.65 g/dL Standard Deviation 1.306	—
Change From Baseline of Erythrocyte MCHC, Hemoglobin Week 4 of cycle 4 - Hemoglobin (g/dL)	—	—	-0.15 g/dL Standard Deviation 0.921	—
Change From Baseline of Erythrocyte MCHC, Hemoglobin Week 4 of cycle 1 - Hemoglobin (g/dL)	0.02 g/dL Standard Deviation 0.732	-0.09 g/dL Standard Deviation 0.740	—	—
Change From Baseline of Erythrocyte MCHC, Hemoglobin Week 4 of cycle 2 - Erythrocyte MCHC (g/dL)	—	—	0.16 g/dL Standard Deviation 1.070	—

SECONDARY outcome

Safety assessments by evaluating change from baseline of Lymphocytes/leukocytes, Monocytes/leukocytes, Neutrophils/leukocytes, Basophiles/leukocytes, Eosinophils/leukocytes as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=250 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=82 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=299 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 1 - Basophiles/leukocytes (%)	0.05 % of leukocytes Standard Deviation 0.669	0.14 % of leukocytes Standard Deviation 0.890	—	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 1 - Eosinophils/leukocytes (%)	0.14 % of leukocytes Standard Deviation 1.090	0.05 % of leukocytes Standard Deviation 1.292	—	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 1 - Lymphocytes/leukocytes (%)	-0.26 % of leukocytes Standard Deviation 6.724	-1.13 % of leukocytes Standard Deviation 5.468	—	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 1 - Monocytes/leukocytes (%)	-0.40 % of leukocytes Standard Deviation 2.337	-0.48 % of leukocytes Standard Deviation 2.350	—	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 1 - Neutrophils/leukocytes (%)	0.47 % of leukocytes Standard Deviation 7.610	1.41 % of leukocytes Standard Deviation 6.219	—	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 2 - Basophiles/leukocytes (%)	—	—	-0.04 % of leukocytes Standard Deviation 0.837	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 2 - Eosinophils/leukocytes (%)	—	—	0.13 % of leukocytes Standard Deviation 1.554	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 2 - Lymphocytes/leukocytes (%)	—	—	0.80 % of leukocytes Standard Deviation 6.802	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 2 - Monocytes/leukocytes (%)	—	—	-0.04 % of leukocytes Standard Deviation 1.559	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 2 - Neutrophils/leukocytes (%)	—	—	-0.84 % of leukocytes Standard Deviation 7.660	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 3 - Basophiles/leukocytes (%)	—	—	-0.25 % of leukocytes Standard Deviation 0.764	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 3 - Eosinophils/leukocytes (%)	—	—	0.06 % of leukocytes Standard Deviation 1.788	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 3 - Lymphocytes/leukocytes (%)	—	—	0.82 % of leukocytes Standard Deviation 7.814	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 3 - Monocytes/leukocytes (%)	—	—	-0.16 % of leukocytes Standard Deviation 1.790	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 3 - Neutrophils/leukocytes (%)	—	—	-0.47 % of leukocytes Standard Deviation 9.240	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 4 - Basophiles/leukocytes (%)	—	—	-0.23 % of leukocytes Standard Deviation 0.663	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 4 - Eosinophils/leukocytes (%)	—	—	-0.26 % of leukocytes Standard Deviation 1.191	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 4 - Lymphocytes/leukocytes (%)	—	—	1.68 % of leukocytes Standard Deviation 6.869	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 4 - Monocytes/leukocytes (%)	—	—	0.06 % of leukocytes Standard Deviation 2.434	—
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes Week 4 of cycle 4 - Neutrophils/leukocytes (%)	—	—	-1.34 % of leukocytes Standard Deviation 7.460	—

SECONDARY outcome

Safety assessments by evaluating change from baseline of Systolic and Diastolic Blood Pressure as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=263 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=85 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=305 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Change From Baseline of Systolic and Diastolic Blood Pressure Week 4 of cycle 2 - Diastolic Blood Pressure (mmHg)	—	—	0.0 mmHg Standard Deviation 7.79	—
Change From Baseline of Systolic and Diastolic Blood Pressure Week 4 of cycle 1 - Systolic Blood Pressure (mmHg)	-0.7 mmHg Standard Deviation 11.13	-0.2 mmHg Standard Deviation 10.50	—	—
Change From Baseline of Systolic and Diastolic Blood Pressure Week 4 of cycle 1 - Diastolic Blood Pressure (mmHg)	-1.0 mmHg Standard Deviation 7.54	1.3 mmHg Standard Deviation 8.16	—	—
Change From Baseline of Systolic and Diastolic Blood Pressure Week 4 of cycle 3 - Systolic Blood Pressure (mmHg)	—	—	-1.7 mmHg Standard Deviation 12.06	—
Change From Baseline of Systolic and Diastolic Blood Pressure Week 4 of cycle 2 - Systolic Blood Pressure (mmHg)	—	—	-0.9 mmHg Standard Deviation 11.66	—
Change From Baseline of Systolic and Diastolic Blood Pressure Week 4 of cycle 3 - Diastolic Blood Pressure (mmHg)	—	—	-0.4 mmHg Standard Deviation 8.02	—
Change From Baseline of Systolic and Diastolic Blood Pressure Week 4 of cycle 4 - Systolic Blood Pressure (mmHg)	—	—	-1.8 mmHg Standard Deviation 13.40	—
Change From Baseline of Systolic and Diastolic Blood Pressure Week 4 of cycle 4 - Diastolic Blood Pressure (mmHg)	—	—	-0.2 mmHg Standard Deviation 7.38	—

SECONDARY outcome

Safety assessments by evaluating change from baseline of Pulse rate as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=263 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=85 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=305 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Change From Baseline of Pulse Rate Cycle 1	-1.7 bpm Standard Deviation 10.83	0.1 bpm Standard Deviation 10.24	—	—
Change From Baseline of Pulse Rate Cycle 2	—	—	1.2 bpm Standard Deviation 9.11	—
Change From Baseline of Pulse Rate Cycle 3	—	—	2.2 bpm Standard Deviation 10.73	—
Change From Baseline of Pulse Rate Cycle 4	—	—	0.7 bpm Standard Deviation 10.73	—

SECONDARY outcome

Timeframe: Week 4 and last visit of Treatment Cycle 1 (End of Cycle procedures), conducted upon confirmation of eligibility for retreatment, assessed starting 12 weeks post-treatment with 4-weekly evaluations up to a max. of 48 weeks post treatment.

Population: The population used consists of all subjects who received at least one injection with study medication and who have data available for the respective visit and category of baseline electrocardiogram interpretation. Participants were analyzed as treated.

Safety assessments by evaluating Electrocardiogram as per the study schedule

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=238 Participants Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=28 Participants Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=77 Participants Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles	Placebo - Abnormal Baseline Electrocardiogram Interpretation n=12 Participants Placebo will be administered in double blind fashion in Treatment Cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area Subjects had an electrocardiogram interpretation of abnormal at baseline.
Number of Participants With Normal and Abnormal Electrocardiogram Cycle 1 Week 4 - Electrocardiogram Interpretation · Normal	223 Participants	5 Participants	71 Participants	3 Participants
Number of Participants With Normal and Abnormal Electrocardiogram Cycle 1 Week 4 - Electrocardiogram Interpretation · Abnormal	13 Participants	22 Participants	3 Participants	8 Participants
Number of Participants With Normal and Abnormal Electrocardiogram Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation · Normal	198 Participants	6 Participants	69 Participants	3 Participants
Number of Participants With Normal and Abnormal Electrocardiogram Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation · Abnormal	10 Participants	19 Participants	4 Participants	8 Participants

Adverse Events

Botulinum Toxin A

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Botulinum Toxin A Open Label Extension Arm

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Botulinum Toxin A n=266 participants at risk Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 participants at risk Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=323 participants at risk Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles
Cardiac disorders Acute myocardial infarction	0.00% 0/266 • Up to 60 weeks post first treatment	0.00% 0/89 • Up to 60 weeks post first treatment	0.31% 1/323 • Number of events 1 • Up to 60 weeks post first treatment
Endocrine disorders Goitre	0.00% 0/266 • Up to 60 weeks post first treatment	0.00% 0/89 • Up to 60 weeks post first treatment	0.31% 1/323 • Number of events 1 • Up to 60 weeks post first treatment
Hepatobiliary disorders Cholecystitis	0.00% 0/266 • Up to 60 weeks post first treatment	0.00% 0/89 • Up to 60 weeks post first treatment	0.31% 1/323 • Number of events 1 • Up to 60 weeks post first treatment
Hepatobiliary disorders Cholelithiasis	0.00% 0/266 • Up to 60 weeks post first treatment	0.00% 0/89 • Up to 60 weeks post first treatment	0.31% 1/323 • Number of events 1 • Up to 60 weeks post first treatment
Musculoskeletal and connective tissue disorders Foot deformity	0.38% 1/266 • Number of events 1 • Up to 60 weeks post first treatment	0.00% 0/89 • Up to 60 weeks post first treatment	0.00% 0/323 • Up to 60 weeks post first treatment
Nervous system disorders Syncope	0.00% 0/266 • Up to 60 weeks post first treatment	1.1% 1/89 • Number of events 1 • Up to 60 weeks post first treatment	0.00% 0/323 • Up to 60 weeks post first treatment
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/266 • Up to 60 weeks post first treatment	0.00% 0/89 • Up to 60 weeks post first treatment	0.31% 1/323 • Number of events 1 • Up to 60 weeks post first treatment

Other adverse events

Other adverse events
Measure	Botulinum Toxin A n=266 participants at risk Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area	Placebo n=89 participants at risk Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area	Botulinum Toxin A Open Label Extension Arm n=323 participants at risk Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles
Infections and infestations Nasopharyngitis	0.75% 2/266 • Number of events 2 • Up to 60 weeks post first treatment	3.4% 3/89 • Number of events 3 • Up to 60 weeks post first treatment	2.8% 9/323 • Number of events 9 • Up to 60 weeks post first treatment
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/266 • Up to 60 weeks post first treatment	2.2% 2/89 • Number of events 2 • Up to 60 weeks post first treatment	0.31% 1/323 • Number of events 1 • Up to 60 weeks post first treatment
Nervous system disorders Headache	3.8% 10/266 • Number of events 10 • Up to 60 weeks post first treatment	2.2% 2/89 • Number of events 2 • Up to 60 weeks post first treatment	1.5% 5/323 • Number of events 5 • Up to 60 weeks post first treatment

Additional Information

Clinical Development - Head of Clinical Operations

Croma Pharma

Phone: +432262684680

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place