Trial Outcomes & Findings for Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study II (NCT NCT02677805)

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

251 participants

Primary outcome timeframe

Week 4

Results posted on

2025-03-19

Participant Flow

Of 251 enrolled participants, 213 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, sodium chloride 0.9 % 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	160	53	0
Double Blind Phase COMPLETED	147	48	0
Double Blind Phase NOT COMPLETED	13	5	0
Open Label Phase STARTED	0	0	195
Open Label Phase COMPLETED	0	0	179
Open Label Phase NOT COMPLETED	0	0	16

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, sodium chloride 0.9 % 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 Lost to Follow-up	8	3	0
Double Blind Phase Withdrawal by Subject	5	2	0
Open Label Phase Lost to Follow-up	0	0	10
Open Label Phase Withdrawal by Subject	0	0	6

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Botulinum Toxin A n=160 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=53 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, sodium chloride 0.9 % divided in five 0.1 mL i.m. injections into glabellar area	Total n=213 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	141 Participants n=5 Participants	45 Participants n=7 Participants	186 Participants n=5 Participants
Age, Categorical >=65 years	19 Participants n=5 Participants	8 Participants n=7 Participants	27 Participants n=5 Participants
Age, Continuous	52.04 years STANDARD_DEVIATION 10.458 • n=5 Participants	52.43 years STANDARD_DEVIATION 10.137 • n=7 Participants	52.14 years STANDARD_DEVIATION 10.357 • n=5 Participants
Sex: Female, Male Female	150 Participants n=5 Participants	45 Participants n=7 Participants	195 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	8 Participants n=7 Participants	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	33 Participants n=5 Participants	7 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	126 Participants n=5 Participants	45 Participants n=7 Participants	171 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	153 Participants n=5 Participants	50 Participants n=7 Participants	203 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	160 Participants n=5 Participants	53 Participants n=7 Participants	213 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	48 Participants n=5 Participants	16 Participants n=7 Participants	64 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	112 Participants n=5 Participants	37 Participants n=7 Participants	149 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	39 Participants n=5 Participants	11 Participants n=7 Participants	50 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	121 Participants n=5 Participants	42 Participants n=7 Participants	163 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=160 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=53 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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	78 Participants	1 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=160 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=53 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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	7 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=149 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=48 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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 16	5 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=160 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=53 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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	95 Participants	3 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	113 Participants	9 Participants	—	—	—

SECONDARY outcome

Timeframe: Week 20, Week 24, Week 28, Week 32

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 visit. They were analyzed as randomized. In addition, only for Week 20 visit participants who were re-treated before week 20 were counted as non-responders in the analysis.

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 the respective 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=148 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=48 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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 Weeks 20, 24, 28 and 32 Week 28	0 Participants	0 Participants	—	—	—
Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 Week 20	2 Participants	0 Participants	—	—	—
Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 Week 24	1 Participants	0 Participants	—	—	—
Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 Week 32	0 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Week 4

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=154 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=49 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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 (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) Modified Skindex-16 (GL-QoL) Emotional domain - Change from Baseline at Week 4	-40.59 score on a scale Standard Deviation 30.511	-4.22 score on a scale Standard Deviation 20.426	—	—	—
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	-33.50 score on a scale Standard Deviation 33.100	-10.38 score on a scale Standard Deviation 20.596	—	—	—
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	-37.55 score on a scale Standard Deviation 29.414	-6.84 score on a scale Standard Deviation 18.238	—	—	—
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	41.56 score on a scale Standard Deviation 26.649	4.84 score on a scale Standard Deviation 17.932	—	—	—
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	-2.49 score on a scale Standard Deviation 3.997	-0.20 score on a scale Standard Deviation 4.158	—	—	—

SECONDARY outcome

Timeframe: Week 1, Week 2, 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=160 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=53 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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 Weeks 1, 2 and 8 Week 8	42 Participants	1 Participants	—	—	—
Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8 Week 1	66 Participants	1 Participants	—	—	—
Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8 Week 2	89 Participants	1 Participants	—	—	—

SECONDARY outcome

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

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 raters' 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=160 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=53 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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 Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs Week 2	91 Participants	1 Participants	—	—	—
Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs Week 4	88 Participants	1 Participants	—	—	—
Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs Week 12	18 Participants	1 Participants	—	—	—
Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs Week 16	4 Participants	0 Participants	—	—	—
Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs Week 20	1 Participants	0 Participants	—	—	—

SECONDARY outcome

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

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=160 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=53 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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, 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=160 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=53 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, sodium chloride 0.9 % divided in five 0.1 mL i.m. injections into glabellar area	Botulinum Toxin A Open Label Extension Arm n=195 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 3 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 3	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 3 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 3 Week 4 - great · 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 - look in mirror · Definitely agree	—	—	67 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	—	—	9 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	—	—	41 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 mirror · Definitely disagree	21 Participants	37 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	53 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 - pleased · Definitely disagree	16 Participants	37 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	6 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 agree	38 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	94 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 - pleased · Missing	6 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	16 Participants	40 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	18 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 · Somewhat agree	43 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 agree	77 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 - expected · Missing	6 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 - great · Definitely disagree	19 Participants	39 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	18 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 - great · Somewhat agree	35 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 - great · Definitely agree	82 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 · Missing	6 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 - look in mirror · Somewhat disagree	25 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 - look in mirror · Somewhat agree	42 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 mirror · Definitely agree	66 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 mirror · Missing	6 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 - fantastic · Definitely disagree	26 Participants	42 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	22 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 agree	38 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	68 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	6 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 - miraculous · Definitely disagree	35 Participants	42 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	30 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 - miraculous · Somewhat agree	36 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 - miraculous · Missing	6 Participants	4 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	—	—	14 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	—	—	16 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	—	—	50 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	—	—	113 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	—	—	2 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	—	—	19 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	—	—	21 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	—	—	62 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	—	—	91 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	—	—	2 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	—	—	21 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	—	—	27 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	—	—	50 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	—	—	95 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	—	—	2 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 mirror · 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 - look in mirror · Somewhat disagree	—	—	39 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 mirror · Somewhat agree	—	—	65 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 mirror · Definitely agree	—	—	72 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 mirror · Missing	—	—	2 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	—	—	28 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	—	—	29 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	—	—	49 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	—	—	87 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	—	—	2 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	—	—	38 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	—	—	32 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	—	—	65 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	—	—	58 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	—	—	2 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	—	—	14 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	—	—	14 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	—	—	37 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	—	—	106 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	—	—	10 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	—	—	18 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	—	—	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 agree	—	—	41 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	—	—	92 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	—	—	10 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	—	—	27 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	—	—	32 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	—	—	96 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	—	—	10 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	—	—	16 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	—	—	32 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	—	—	56 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	—	—	10 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	—	—	24 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	—	—	32 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	—	—	41 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	—	—	74 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	—	—	10 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	—	—	40 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	—	—	31 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	—	—	45 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	—	—	55 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	—	—	10 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	—	—	15 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	—	—	84 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	—	—	0 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	—	—	19 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	—	—	20 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	—	—	76 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	—	—	0 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	—	—	20 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	—	—	27 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	—	—	27 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	—	—	75 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	—	—	0 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 mirror · Definitely 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 mirror · Somewhat disagree	—	—	33 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 mirror · Somewhat 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 - look in mirror · Definitely agree	—	—	57 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 mirror · Missing	—	—	0 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	—	—	29 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	—	—	26 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	—	—	33 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	—	—	61 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	—	—	0 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	—	—	42 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	—	—	27 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	—	—	36 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	—	—	44 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	—	—	0 Participants	—	—

SECONDARY outcome

Timeframe: Week 2, Week 4, Week 12, Week 16, Week 20, Week 24, Week 28

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 raters' assessment of photographs. 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=160 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=53 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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 Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs Week 2	45 Participants	7 Participants	—	—	—
Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs Week 4	53 Participants	8 Participants	—	—	—
Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs Week 12	41 Participants	6 Participants	—	—	—
Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs Week 16	6 Participants	0 Participants	—	—	—
Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs Week 20	2 Participants	0 Participants	—	—	—
Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs Week 24	2 Participants	0 Participants	—	—	—
Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs 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 in the respective treatment cycle 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 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=195 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, sodium chloride 0.9 % 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	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 3 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 3	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 3 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 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 Week 4 after 1st Re-treatment	73 Participants	—	—	—	—
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 Week 4 after 2nd Re-treatment	47 Participants	—	—	—	—
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 Week 4 after 3rd Re-treatment	44 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.

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=160 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=53 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, sodium chloride 0.9 % divided in five 0.1 mL i.m. injections into glabellar area	Botulinum Toxin A Open Label Extension Arm n=195 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 3 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 3	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 3 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 AEs of Special Interest (AESIs) Subjects with any Treatment Emergent Adverse Event (TEAE)	38 Participants	7 Participants	50 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	5 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 Injection Procedure Related TEAE	2 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 any Severe TEAE	1 Participants	0 Participants	1 Participants	—	—
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) Subjects with any Serious TEAE	0 Participants	0 Participants	2 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)	3 Participants	0 Participants	1 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.