Trial Outcomes & Findings for Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study I (NCT NCT02677298)

Last Updated: 2025-03-19

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

784 participants

Primary outcome timeframe

Week 4

Results posted on

2025-03-19

Participant Flow

Of 784 enrolled participants, 708 met inclusion criteria and were randomized to treatment.

Participant milestones

Participant milestones
Measure	Botulinum Toxin A Botulinum Toxin A (Clostridium botulinum toxin type 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 the 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 i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1 mL i.m. injections into 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	531	177	0
Double Blind Phase Received Treatment	529	175	0
Double Blind Phase COMPLETED	502	160	0
Double Blind Phase NOT COMPLETED	29	17	0
Open Label Phase STARTED	0	0	659
Open Label Phase COMPLETED	0	0	599
Open Label Phase NOT COMPLETED	0	0	60

Reasons for withdrawal

Reasons for withdrawal
Measure	Botulinum Toxin A Botulinum Toxin A (Clostridium botulinum toxin type 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 the 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 i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1 mL i.m. injections into 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 Adverse Event	2	1	0
Double Blind Phase Physician Decision	5	0	0
Double Blind Phase Lost to Follow-up	11	7	0
Double Blind Phase Withdrawal by Subject	11	8	0
Double Blind Phase No study drug available at site	0	1	0
Open Label Phase Adverse Event	0	0	4
Open Label Phase Physician Decision	0	0	1
Open Label Phase Lost to Follow-up	0	0	17
Open Label Phase Withdrawal by Subject	0	0	38

Baseline Characteristics

Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study I

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Botulinum Toxin A n=529 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=175 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into glabellar area	Total n=704 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	463 Participants n=5 Participants	157 Participants n=7 Participants	620 Participants n=5 Participants
Age, Categorical >=65 years	66 Participants n=5 Participants	18 Participants n=7 Participants	84 Participants n=5 Participants
Age, Continuous	49.25 years STANDARD_DEVIATION 11.984 • n=5 Participants	48.74 years STANDARD_DEVIATION 11.378 • n=7 Participants	49.13 years STANDARD_DEVIATION 11.830 • n=5 Participants
Sex: Female, Male Female	463 Participants n=5 Participants	157 Participants n=7 Participants	620 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants	18 Participants n=7 Participants	84 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	25 Participants n=5 Participants	8 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	498 Participants n=5 Participants	166 Participants n=7 Participants	664 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	6 Participants n=5 Participants	1 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	3 Participants n=7 Participants	11 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	33 Participants n=5 Participants	18 Participants n=7 Participants	51 Participants n=5 Participants
Race (NIH/OMB) White	482 Participants n=5 Participants	153 Participants n=7 Participants	635 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	269 participants n=5 Participants	95 participants n=7 Participants	364 participants n=5 Participants
Region of Enrollment Germany	139 participants n=5 Participants	41 participants n=7 Participants	180 participants n=5 Participants
Region of Enrollment Poland	121 participants n=5 Participants	39 participants n=7 Participants	160 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	145 Participants n=5 Participants	42 Participants n=7 Participants	187 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	384 Participants n=5 Participants	133 Participants n=7 Participants	517 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	1 Participants n=5 Participants	0 Participants n=7 Participants	1 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	127 Participants n=5 Participants	54 Participants n=7 Participants	181 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	401 Participants n=5 Participants	121 Participants n=7 Participants	522 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 4

Population: The population used consists of all randomized subjects, who received at least one injection with 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=529 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=175 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
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.	246 Participants	0 Participants	—	—	—

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=529 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=175 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
Percentage of Responders at Maximum Frown at Week 12	67 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Week 16

Population: The population used consists of all randomized subjects who received at least one injection with study medication and 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=501 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=159 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
Percentage of Responders at Week 16	22 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Week 4

Population: The population used consists of all randomized subjects who received at least one injection with study medication and who had 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=529 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=175 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
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	334 Participants	27 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	412 Participants	17 Participants	—	—	—

SECONDARY outcome

Timeframe: Week 20, 24, 28, 32 of Treatment Cycle 1

Population: The week 20 analysis population includes all randomized subjects who received at least one injection with study medication and have data available or were re-treated before week 20, with re-treated participants counted as non-responders. Post-week 20 analysis includes all randomized subjects with at least one injection with study medication, available data for the respective visit, and no re-treatment before that visit.

Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement ≥2 points in FWS score (at maximum frown) at the week 20 visit (or later) relative to baseline, based on both the investigator's and the subject's in-clinic assessment 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 or later in 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=529 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=175 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
Percentage of Responders at Week 20 or Later (After the First Treatment). Week 20	6 Participants	0 Participants	—	—	—
Percentage of Responders at Week 20 or Later (After the First Treatment). Week 24	1 Participants	0 Participants	—	—	—
Percentage of Responders at Week 20 or Later (After the First Treatment). Week 28	0 Participants	0 Participants	—	—	—
Percentage of Responders at Week 20 or Later (After the First Treatment). Week 32	0 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Week 4

Population: The population used consists of all randomized subjects, who received at least one injection with study medication and who have data available for week 4. 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=522 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=168 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
Extent of Change in Psychological Impact Modified Skindex-16 (GL-QoL) Emotional domain - Change from Baseline at Week 4	-32.74 units on a scale Standard Deviation 31.134	0.63 units on a scale Standard Deviation 16.997	—	—	—
Extent of Change in Psychological Impact Modified Skindex-16 (GL-QoL) Social Functioning domain - Change from Baseline at Week 4	-27.44 units on a scale Standard Deviation 30.358	-1.14 units on a scale Standard Deviation 22.041	—	—	—
Extent of Change in Psychological Impact Modified Skindex-16 (GL-QoL) Overall score - Change from Baseline at Week 4	-30.47 units on a scale Standard Deviation 28.707	-0.14 units on a scale Standard Deviation 16.637	—	—	—
Extent of Change in Psychological Impact FACE-Q Appraisal of Lines Between Eyebrows - Change from Baseline at Week 4	37.80 units on a scale Standard Deviation 25.917	-2.05 units on a scale Standard Deviation 14.913	—	—	—
Extent of Change in Psychological Impact Age Appraisal VAS - Change from Baseline at Week 4	-2.45 units on a scale Standard Deviation 4.531	-0.27 units on a scale Standard Deviation 3.379	—	—	—

SECONDARY outcome

Timeframe: Week 1, Week 2, and Week 8

Population: The population used consists of all randomized subjects, who received at least one injection with study medication (independent of whether it is BoNT/A-DP or placebo). Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale (FWS) at baseline or the respective visit were assigned as being non-responders.

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=529 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=175 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
Responder Rate at Weeks 1, 2 and 8 Week 1	207 Participants	0 Participants	—	—	—
Responder Rate at Weeks 1, 2 and 8 Week 2	265 Participants	0 Participants	—	—	—
Responder Rate at Weeks 1, 2 and 8 Week 8	152 Participants	0 Participants	—	—	—

SECONDARY outcome

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

Population: The population used consists of all randomized subjects, who received at least one injection with study medication and for whom independent rater's assessments of photographs are available for the respective timepoint. Participants were analyzed as randomized. The median of all assessments for the same photograph were taken into account.

The percentage of subjects with ≥ 2-point 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). 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=511 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=164 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
The Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Week 2	351 Participants	4 Participants	—	—	—
The Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Week 4	323 Participants	5 Participants	—	—	—
The Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Week 12	48 Participants	2 Participants	—	—	—
The Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Week 16	23 Participants	0 Participants	—	—	—
The Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Week 20	11 Participants	0 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 who received at least one injection with study drug. 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=529 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=175 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
Time to Onset of Effect in the BoNT/A-DP and Placebo Groups in the First Treatment Cycle	8.0 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: Week 4 of Treatment Cycles 1, 2, 3 and 4

Population: The population used consists of all randomized subjects, who received at least one injection with study medication in the respective treatment cycle. 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, at week 4 of 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=529 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=175 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into glabellar area	Botulinum Toxin A Open Label Extension Arm n=659 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
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	52 Participants	143 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	320 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 - expected · Definitely disagree	56 Participants	139 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	130 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 - great · Definitely agree	272 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 · Somewhat disagree	71 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 · Missing	7 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 disagree	72 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 - miraculous · Definitely disagree	107 Participants	155 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	187 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 - miraculous · Definitely agree	133 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 - miraculous · Missing	7 Participants	7 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	—	—	40 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	—	—	37 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	—	—	398 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	—	—	44 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	—	—	93 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	—	—	57 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	—	—	180 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	—	—	29 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	—	—	50 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	—	—	65 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	—	—	214 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	61 Participants	6 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	29 Participants	9 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	121 Participants	12 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	7 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 disagree	51 Participants	12 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	169 Participants	13 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	246 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 - expected · Missing	7 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 · Definitely disagree	59 Participants	151 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	7 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 - look in the mirror · Definitely disagree	65 Participants	146 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	198 Participants	9 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	188 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 · Definitely disagree	80 Participants	152 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	164 Participants	6 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	206 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 · Missing	7 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 - miraculous · Somewhat disagree	95 Participants	5 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	—	—	166 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	—	—	18 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	—	—	83 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	—	—	159 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	—	—	355 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	—	—	18 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	—	—	54 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	—	—	78 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	—	—	151 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	—	—	357 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	—	—	19 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	—	—	55 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	—	—	90 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	—	—	249 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	—	—	247 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	—	—	18 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	—	—	77 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	—	—	202 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	—	—	269 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	—	—	18 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	—	—	114 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	—	—	114 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	—	—	223 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	—	—	190 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	—	—	18 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	—	—	36 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	—	—	38 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	—	—	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 · Definitely agree	—	—	347 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	—	—	29 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	—	—	42 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	—	—	308 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	—	—	174 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	—	—	296 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	—	—	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 mirror · 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 - look in mirror · Somewhat disagree	—	—	96 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 mirror · Somewhat agree	—	—	221 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 mirror · Definitely agree	—	—	218 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 mirror · Missing	—	—	29 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	—	—	70 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	—	—	92 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	—	—	194 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	—	—	231 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	—	—	29 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	—	—	109 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	—	—	97 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	—	—	167 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	—	—	29 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	—	—	30 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	—	—	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 · Somewhat agree	—	—	140 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	—	—	254 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	—	—	3 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	—	—	37 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	—	—	51 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	—	—	159 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	—	—	214 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	—	—	3 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	—	—	50 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	—	—	62 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	—	—	138 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	—	—	211 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	—	—	3 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	—	—	41 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	—	—	88 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	—	—	175 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	—	—	157 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	—	—	3 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	—	—	58 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	—	—	97 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	—	—	154 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	—	—	152 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	—	—	3 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	—	—	92 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	—	—	97 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	—	—	152 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	—	—	120 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	—	—	3 Participants	—	—

SECONDARY outcome

Timeframe: Week 2, 4, 12, 16, 20, 24 and 28 of Treatment Cycle 1

Population: The population used consists of all randomized subjects, who received at least one injection with study medication and for whom independent rater's assessments of photographs were performed. Participants were analyzed as randomized. The median of all assessments for the same photograph were taken into account.

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. 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=529 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=175 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
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	184 Participants	18 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	166 Participants	19 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	93 Participants	22 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	30 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	9 Participants	1 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 24	6 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 28	1 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Week 4 of Treatment Cycles 2, 3 and 4

Population: The population used consists of all randomized subjects who received at least one injection with study medication and 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=659 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the 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 i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
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	245 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	187 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	104 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Through study completion (60 weeks)

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

Frequency, severity and causal relationship of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) during the entire study period.

Outcome measures

Outcome measures
Measure	Botulinum Toxin A n=529 Participants Botulinum Toxin A (Clostridium botulinum toxin type 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 the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.	Placebo n=175 Participants Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area. Placebo: Injection, 0.9% sodium chloride divided in five 0.1mL i.m. injections into glabellar area	Botulinum Toxin A Open Label Extension Arm n=659 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	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 3. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle	Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to three additional treatment cycles. This arm is designated for Study Treatment Cycle 4. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in Treatment Cycle 4
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and Adverse Events of Special Interest (AESIs) Events of Special Interest (AESIs) Subjects with any Treatment Emergent Adverse Event (TEAE)	129 Participants	39 Participants	268 Participants	—	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and Adverse Events of Special Interest (AESIs) Events of Special Interest (AESIs) Subjects with any Study Medication Related TEAE	19 Participants	4 Participants	31 Participants	—	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and Adverse Events of Special Interest (AESIs) Events of Special Interest (AESIs) Subjects with any Injection Procedure Related TEAE	22 Participants	8 Participants	29 Participants	—	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and Adverse Events of Special Interest (AESIs) Events of Special Interest (AESIs) Subjects with any Severe TEAE	12 Participants	3 Participants	17 Participants	—	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and Adverse Events of Special Interest (AESIs) Events of Special Interest (AESIs) Subjects with any Serious TEAE	9 Participants	0 Participants	15 Participants	—	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and Adverse Events of Special Interest (AESIs) Events of Special Interest (AESIs) Subjects with any Adverse Events of Special Interest (AESI)	1 Participants	1 Participants	3 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