Trial Outcomes & Findings for Safety and Efficacy of NT 201 (IncobotulinumtoxinA [Xeomin]) in the Treatment of Glabellar Frown Lines (NCT NCT00512135)

NCT ID: NCT00512135

Last Updated: 2021-04-02

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

801 participants

Primary outcome timeframe

Baseline up to Month 30

Results posted on

2021-04-02

Participant Flow

Participants with moderate to severe glabellar frown lines at maximum frown who completed one of the four feeder studies MRZ 60201-0520/1 (NCT00430963), MRZ 60201-0527/1 (NCT00430586), MRZ 60201-0724/1 (NCT00512135), or MRZ 60201-0741/1(NCT00512135) were enrolled in this repeat-dose study at 26 investigational sites in the United States, Canada and Germany.

A total of 810 participants were screened, out of which 801 were enrolled into the study. Of these 801 participants, 796 received the study treatment.

Participant milestones

Participant milestones
Measure	IncobotulinumtoxinA 20 U Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 units (U) in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 centimeter (cm) above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length greater than or equal to (\>=) 85 days.
Overall Study STARTED	801
Overall Study Treated	796
Overall Study COMPLETED	717
Overall Study NOT COMPLETED	84

Reasons for withdrawal

Reasons for withdrawal
Measure	IncobotulinumtoxinA 20 U Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 units (U) in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 centimeter (cm) above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length greater than or equal to (\>=) 85 days.
Overall Study Not Treated	5
Overall Study Lack of Efficacy	2
Overall Study Adverse Event	6
Overall Study Withdrawal by Subject	22
Overall Study Lost to Follow-up	27
Overall Study Other	22

Baseline Characteristics

Safety and Efficacy of NT 201 (IncobotulinumtoxinA [Xeomin]) in the Treatment of Glabellar Frown Lines

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IncobotulinumtoxinA 20 U n=796 Participants Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm) above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length \>=85 days.
Age, Continuous	46.6 years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	702 Participants n=5 Participants
Sex: Female, Male Male	94 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	26 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	10 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	81 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race/Ethnicity, Customized White	669 Participants n=5 Participants
Race/Ethnicity, Customized Other	8 Participants n=5 Participants
Region of Enrollment Europe	177 Participants n=5 Participants
Region of Enrollment North America	619 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up to Month 30

Population: The FAS consisted of all participants who were successfully screened for the study (signed the ICF) and received at least one injection of the study drug.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 20 U n=796 Participants Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length \>=85 days.
Incidence of Adverse Events (AEs)	374 Participants

PRIMARY outcome

Timeframe: Baseline up to Month 30

Population: The FAS consisted of all participants who were successfully screened for the study (signed the ICF) and received at least one injection of the study drug.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 20 U n=796 Participants Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length \>=85 days.
Incidence of Adverse Events of Special Interest (AESI)	9 Participants

PRIMARY outcome

Timeframe: At evaluation visit (30 days after injection) and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

Population: The FAS consisted of all participants who were successfully screened for the study (signed the ICF) and received at least one injection of the study drug. Here number analyzed "n" were the participants who were evaluable for this outcome measure at given time points.

FWS was used to assess the severity of glabellar frown lines at maximum frown by the investigator. The 4-point scale depicted as: 0 = none, 1 = mild, 2 = moderate and 3 = severe. Responders on the FWS were defined as participants with glabellar line severity of none (0) or mild (1).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 20 U n=796 Participants Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length \>=85 days.
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 6: Last Control Visit	8.8 percentage of participants Interval 5.9 to 12.9
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 1: Evaluation Visit	79.1 percentage of participants Interval 76.2 to 81.8
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 2: Evaluation Visit	79.8 percentage of participants Interval 76.7 to 82.6
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 3: Evaluation Visit	80.1 percentage of participants Interval 75.4 to 84.1
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 4: Evaluation Visit	80.3 percentage of participants Interval 75.5 to 84.3
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 5: Evaluation Visit	81.4 percentage of participants Interval 76.6 to 85.5
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 6: Evaluation Visit	81.2 percentage of participants Interval 76.0 to 85.5
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 7: Evaluation Visit	82.7 percentage of participants Interval 76.7 to 87.4
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 8: Evaluation Visit	89.6 percentage of participants Interval 77.8 to 95.5
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 1: Last Control Visit	6.5 percentage of participants Interval 5.0 to 8.5
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 2: Last Control Visit	16.6 percentage of participants Interval 14.0 to 19.5
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 3: Last Control Visit	0.6 percentage of participants Interval 0.2 to 2.2
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 4: Last Control Visit	0.6 percentage of participants Interval 0.2 to 2.3
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 5: Last Control Visit	4.8 percentage of participants Interval 2.9 to 7.9
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 7: Last Control Visit	17.8 percentage of participants Interval 13.0 to 23.8
Percentage of Responders at Maximum Frown as Assessed by the Investigator According to Facial Wrinkle Scale (FWS) Cycle 8: Last Control Visit	29.2 percentage of participants Interval 18.2 to 43.2

PRIMARY outcome

Timeframe: At evaluation visit (30 days after injection) and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

FWS was used to assess the severity of glabellar frown lines at rest by the investigator. The 4-point scale depicted as: 0 = none, 1 = mild, 2 = moderate and 3 = severe. Responders on the FWS were defined as participants with glabellar line severity of none (0) or mild (1). Responders on the FWS were defined as participants with glabellar line severity of none (0) or mild (1).

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 20 U n=796 Participants Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length \>=85 days.
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 8: Last Control Visit	83.3 percentage of participants Interval 70.4 to 91.3
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 1: Evaluation Visit	78.9 percentage of participants Interval 75.9 to 81.6
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 2: Evaluation Visit	79.7 percentage of participants Interval 76.5 to 82.5
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 3: Evaluation Visit	80.7 percentage of participants Interval 76.1 to 84.7
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 4: Evaluation Visit	80.6 percentage of participants Interval 75.8 to 84.6
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 5: Evaluation Visit	79.4 percentage of participants Interval 74.4 to 83.6
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 6: Evaluation Visit	77.0 percentage of participants Interval 71.5 to 81.7
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 7: Evaluation Visit	81.2 percentage of participants Interval 75.0 to 86.1
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 8: Evaluation Visit	87.5 percentage of participants Interval 75.3 to 94.1
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 1: Last Control Visit	57.0 percentage of participants Interval 53.6 to 60.4
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 2: Last Control Visit	63.8 percentage of participants Interval 60.2 to 67.3
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 3: Last Control Visit	63.7 percentage of participants Interval 58.3 to 68.7
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 4: Last Control Visit	60.5 percentage of participants Interval 55.0 to 65.8
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 5: Last Control Visit	63.2 percentage of participants Interval 57.6 to 68.6
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 6: Last Control Visit	64.4 percentage of participants Interval 58.4 to 69.9
Percentage of Responders at Rest as Assessed by the Investigator According to FWS Cycle 7: Last Control Visit	67.0 percentage of participants Interval 60.1 to 73.3

PRIMARY outcome

Timeframe: At evaluation visit (30 days after injection) and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

Participant's assessment of the glabellar frown lines at maximum frown on the 4-point scale was done by asking participant the following question in local language: "How would you judge the potency of frown muscle action by comparison to sample photos at this visit?" The possible rating responses were: 0 = no muscle action at all, 1 = some even slight muscle action possible, 2 = moderately strong muscle action possible, 3 = strong muscle action possible which may cause local pallor. Responders were participants with at least 1-point improvement compared to Day 0 whereas improvement was expressed by lowering of the numerical score.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 20 U n=796 Participants Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length \>=85 days.
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 1: Evaluation Visit	86.2 percentage of participants Interval 83.6 to 88.4
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 2: Evaluation Visit	87.6 percentage of participants Interval 84.9 to 89.9
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 3: Evaluation Visit	88.2 percentage of participants Interval 84.2 to 91.3
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 4: Evaluation Visit	87.4 percentage of participants Interval 83.2 to 90.6
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 5: Evaluation Visit	85.9 percentage of participants Interval 81.4 to 89.4
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 6: Evaluation Visit	88.5 percentage of participants Interval 84.1 to 91.8
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 7: Evaluation Visit	90.1 percentage of participants Interval 85.0 to 93.5
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 8: Evaluation Visit	93.8 percentage of participants Interval 83.2 to 97.9
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 1: Last Control Visit	31.2 percentage of participants Interval 28.0 to 34.5
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 2: Last Control Visit	43.8 percentage of participants Interval 40.2 to 47.5
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 3: Last Control Visit	38.2 percentage of participants Interval 33.1 to 43.6
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 4: Last Control Visit	37.9 percentage of participants Interval 32.6 to 43.4
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 5: Last Control Visit	43.6 percentage of participants Interval 38.1 to 49.4
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 6: Last Control Visit	41.8 percentage of participants Interval 35.9 to 47.8
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 7: Last Control Visit	52.4 percentage of participants Interval 45.3 to 59.3
Percentage of Responders at Maximum Frown by Participant's Assessment on the 4-point Scale Cycle 8: Last Control Visit	60.4 percentage of participants Interval 46.3 to 73.0

PRIMARY outcome

Timeframe: At evaluation visit (30 days after injection) and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

Participant's assessment of the glabellar frown lines at rest on the 4-point scale was done by asking participant the following question in local language: "How would you judge the degree of your glabellar lines by comparison to sample photos at this visit?" The possible rating responses were: 0 = no visible vertical line(s) at all, 1 = slightly visible vertical line(s), 2 = moderate vertical line(s) with depression, and 3 = deep vertical line(s) and depression which cannot be effaced by spreading. Responders were participants with at least 1-point improvement compared to Day 0 whereas improvement was expressed by lowering of the numerical score.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 20 U n=796 Participants Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length \>=85 days.
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 1: Evaluation Visit	69.5 percentage of participants Interval 66.2 to 72.6
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 2: Evaluation Visit	67.0 percentage of participants Interval 63.4 to 70.4
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 3: Evaluation Visit	73.0 percentage of participants Interval 67.9 to 77.5
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 4: Evaluation Visit	73.8 percentage of participants Interval 68.6 to 78.4
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 5: Evaluation Visit	77.0 percentage of participants Interval 71.8 to 81.4
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 6: Evaluation Visit	75.1 percentage of participants Interval 69.5 to 80.0
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 7: Evaluation Visit	75.9 percentage of participants Interval 69.4 to 81.4
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 8: Evaluation Visit	77.1 percentage of participants Interval 63.5 to 86.7
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 1: Last Control Visit	35.1 percentage of participants Interval 31.8 to 38.4
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 2: Last Control Visit	43.2 percentage of participants Interval 39.6 to 46.9
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 3: Last Control Visit	38.8 percentage of participants Interval 33.7 to 44.2
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 4: Last Control Visit	42.1 percentage of participants Interval 36.7 to 47.6
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 5: Last Control Visit	43.6 percentage of participants Interval 38.1 to 49.4
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 6: Last Control Visit	49.0 percentage of participants Interval 43.0 to 55.1
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 7: Last Control Visit	54.5 percentage of participants Interval 47.4 to 61.4
Percentage of Responders at Rest by Participant's Assessment on the 4-point Scale Cycle 8: Last Control Visit	58.3 percentage of participants Interval 44.3 to 71.2

PRIMARY outcome

Timeframe: At evaluation visit (30 days after injection); and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

Population: The FAS consisted of all participants who were successfully screened for the study (signed the ICF) and received at least one injection of the study drug. Here "overall participants analyzed" are participants who were available for this outcome measure assessment and number analyzed "n" were the participants who were evaluable for this outcome measure at given time categories.

Number of participants are reported categorized in grades based on the assessment of the glabellar frown lines at maximum frown on the 6-point Likert scale. Participant's assessment of the glabellar frown lines at maximum frown on the 6-point Likert type scale was done by asking participant the following question in local language: "How would you judge the potency of frown muscle action at this visit?" The possible rating responses were given on a categorical scale of 6 grades between the grades 0 = none at all and 5 = very deep, with higher score reflecting higher potency.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 20 U n=786 Participants Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length \>=85 days.
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Evaluation Visit · Grade 0	118 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Evaluation Visit · Grade 1	256 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Evaluation Visit · Grade 2	210 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Evaluation Visit · Grade 3	140 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Evaluation Visit · Grade 4	46 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Evaluation Visit · Grade 5	16 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Evaluation Visit · Grade 0	99 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Evaluation Visit · Grade 1	228 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Evaluation Visit · Grade 2	187 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Evaluation Visit · Grade 3	114 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Evaluation Visit · Grade 4	39 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Evaluation Visit · Grade 5	23 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Evaluation Visit · Grade 0	52 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Evaluation Visit · Grade 1	113 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Evaluation Visit · Grade 2	84 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Evaluation Visit · Grade 3	44 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Evaluation Visit · Grade 4	19 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Evaluation Visit · Grade 5	7 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Evaluation Visit · Grade 0	57 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Evaluation Visit · Grade 1	96 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Evaluation Visit · Grade 2	83 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Evaluation Visit · Grade 3	49 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Evaluation Visit · Grade 4	16 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Evaluation Visit · Grade 5	4 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Evaluation Visit · Grade 0	51 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Evaluation Visit · Grade 1	98 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Evaluation Visit · Grade 2	84 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Evaluation Visit · Grade 3	35 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Evaluation Visit · Grade 4	19 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Evaluation Visit · Grade 5	3 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Evaluation Visit · Grade 0	44 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Evaluation Visit · Grade 1	95 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Evaluation Visit · Grade 2	64 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Evaluation Visit · Grade 3	39 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Evaluation Visit · Grade 4	14 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Evaluation Visit · Grade 5	3 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Evaluation Visit · Grade 0	25 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Evaluation Visit · Grade 1	74 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Evaluation Visit · Grade 2	49 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Evaluation Visit · Grade 3	32 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Evaluation Visit · Grade 4	9 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Evaluation Visit · Grade 5	1 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Evaluation Visit · Grade 0	5 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Evaluation Visit · Grade 1	22 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Evaluation Visit · Grade 2	14 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Evaluation Visit · Grade 3	5 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Evaluation Visit · Grade 4	1 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Evaluation Visit · Grade 5	1 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Last Control Visit · Grade 0	6 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Last Control Visit · Grade 1	28 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Last Control Visit · Grade 2	99 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Last Control Visit · Grade 3	223 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Last Control Visit · Grade 4	259 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 1: Last Control Visit · Grade 5	162 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Last Control Visit · Grade 0	9 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Last Control Visit · Grade 1	54 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Last Control Visit · Grade 2	97 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Last Control Visit · Grade 3	208 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Last Control Visit · Grade 4	208 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 2: Last Control Visit · Grade 5	105 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Last Control Visit · Grade 0	0 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Last Control Visit · Grade 1	10 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Last Control Visit · Grade 2	49 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Last Control Visit · Grade 3	100 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Last Control Visit · Grade 4	114 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 3: Last Control Visit · Grade 5	44 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Last Control Visit · Grade 0	0 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Last Control Visit · Grade 1	14 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Last Control Visit · Grade 2	41 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Last Control Visit · Grade 3	104 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Last Control Visit · Grade 4	90 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 4: Last Control Visit · Grade 5	55 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Last Control Visit · Grade 0	1 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Last Control Visit · Grade 1	16 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Last Control Visit · Grade 2	55 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Last Control Visit · Grade 3	89 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Last Control Visit · Grade 4	81 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 5: Last Control Visit · Grade 5	45 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Last Control Visit · Grade 0	2 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Last Control Visit · Grade 1	16 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Last Control Visit · Grade 2	52 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Last Control Visit · Grade 3	73 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Last Control Visit · Grade 4	83 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 6: Last Control Visit · Grade 5	31 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Last Control Visit · Grade 0	3 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Last Control Visit · Grade 1	16 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Last Control Visit · Grade 2	50 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Last Control Visit · Grade 3	51 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Last Control Visit · Grade 4	52 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 7: Last Control Visit · Grade 5	17 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Last Control Visit · Grade 0	0 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Last Control Visit · Grade 1	4 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Last Control Visit · Grade 2	14 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Last Control Visit · Grade 3	13 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Last Control Visit · Grade 4	13 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Maximum Frown Cycle 8: Last Control Visit · Grade 5	4 Participants

PRIMARY outcome

Timeframe: At evaluation visit (30 days after injection); and at last control visit (85 days after last injection) in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

Number of participants are reported categorized in grades based on the assessment of the glabellar frown lines at rest on the 6-point Likert scale. Participant's assessment of the glabellar frown lines at rest on the 6-point Likert type scale was done by asking participant the following question in local language: "How would you judge the degree of your glabellar lines at this visit?" The possible rating responses were given on a categorical scale of 6 grades between the grades 0 = none at all and 5 = very deep, with higher scores reflecting higher degree of glabellar lines.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 20 U n=786 Participants Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length \>=85 days.
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Evaluation Visit · Grade 0	237 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Evaluation Visit · Grade 1	281 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Evaluation Visit · Grade 2	144 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Evaluation Visit · Grade 3	89 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Evaluation Visit · Grade 4	28 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Evaluation Visit · Grade 5	7 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Evaluation Visit · Grade 0	205 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Evaluation Visit · Grade 1	251 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Evaluation Visit · Grade 2	150 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Evaluation Visit · Grade 3	57 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Evaluation Visit · Grade 4	15 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Evaluation Visit · Grade 5	12 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Evaluation Visit · Grade 0	98 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Evaluation Visit · Grade 1	111 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Evaluation Visit · Grade 2	72 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Evaluation Visit · Grade 3	29 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Evaluation Visit · Grade 4	5 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Evaluation Visit · Grade 5	4 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Evaluation Visit · Grade 0	90 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Evaluation Visit · Grade 1	123 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Evaluation Visit · Grade 2	53 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Evaluation Visit · Grade 3	34 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Evaluation Visit · Grade 4	2 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Evaluation Visit · Grade 5	3 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Evaluation Visit · Grade 0	92 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Evaluation Visit · Grade 1	111 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Evaluation Visit · Grade 2	52 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Evaluation Visit · Grade 3	25 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Evaluation Visit · Grade 4	7 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Evaluation Visit · Grade 5	3 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Evaluation Visit · Grade 0	80 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Evaluation Visit · Grade 1	102 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Evaluation Visit · Grade 2	55 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Evaluation Visit · Grade 3	13 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Evaluation Visit · Grade 4	6 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Evaluation Visit · Grade 5	3 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Evaluation Visit · Grade 0	59 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Evaluation Visit · Grade 1	76 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Evaluation Visit · Grade 2	37 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Evaluation Visit · Grade 3	12 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Evaluation Visit · Grade 4	3 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Evaluation Visit · Grade 5	3 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Evaluation Visit · Grade 0	12 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Evaluation Visit · Grade 1	27 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Evaluation Visit · Grade 2	6 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Evaluation Visit · Grade 3	2 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Evaluation Visit · Grade 4	1 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Evaluation Visit · Grade 5	0 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Last Control Visit · Grade 0	70 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Last Control Visit · Grade 1	204 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Last Control Visit · Grade 2	241 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Last Control Visit · Grade 3	163 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Last Control Visit · Grade 4	71 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 1: Last Control Visit · Grade 5	28 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Last Control Visit · Grade 0	98 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Last Control Visit · Grade 1	199 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Last Control Visit · Grade 2	190 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Last Control Visit · Grade 3	125 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Last Control Visit · Grade 4	50 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 2: Last Control Visit · Grade 5	19 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Last Control Visit · Grade 0	31 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Last Control Visit · Grade 1	81 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Last Control Visit · Grade 2	88 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Last Control Visit · Grade 3	81 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Last Control Visit · Grade 4	24 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 3: Last Control Visit · Grade 5	12 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Last Control Visit · Grade 0	32 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Last Control Visit · Grade 1	88 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Last Control Visit · Grade 2	82 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Last Control Visit · Grade 3	65 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Last Control Visit · Grade 4	30 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 4: Last Control Visit · Grade 5	7 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Last Control Visit · Grade 0	33 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Last Control Visit · Grade 1	71 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Last Control Visit · Grade 2	96 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Last Control Visit · Grade 3	55 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Last Control Visit · Grade 4	25 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 5: Last Control Visit · Grade 5	7 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Last Control Visit · Grade 0	34 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Last Control Visit · Grade 1	73 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Last Control Visit · Grade 2	90 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Last Control Visit · Grade 3	35 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Last Control Visit · Grade 4	20 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 6: Last Control Visit · Grade 5	5 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Last Control Visit · Grade 0	33 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Last Control Visit · Grade 1	64 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Last Control Visit · Grade 2	54 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Last Control Visit · Grade 3	24 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Last Control Visit · Grade 4	10 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 7: Last Control Visit · Grade 5	4 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Last Control Visit · Grade 0	3 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Last Control Visit · Grade 1	24 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Last Control Visit · Grade 2	10 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Last Control Visit · Grade 3	5 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Last Control Visit · Grade 4	6 Participants
Degree of Glabellar Lines as Assessed by the Participant on the 6-point Likert Type Scale at Rest Cycle 8: Last Control Visit · Grade 5	0 Participants

PRIMARY outcome

Timeframe: From injection visit up to date of onset of treatment effect in each treatment cycle from Cycle 1 to Cycle 8 (each cycle length >=85 days)

Population: The FAS consists of all participants who were successfully screened for the study (signed the ICF) and received at least one injection of the study drug. Here overall number analyzed "N" are the participants who were evaluable for the outcome measure and number analyzed "n" were the participants who were evaluable for this outcome measure at given time points.

Onset of treatment effect was analyzed using number of participants with corresponding onset of treatment effect, stratified by cycles.

Outcome measures

Outcome measures
Measure	IncobotulinumtoxinA 20 U n=786 Participants Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length \>=85 days.
Time to Onset of Treatment Effect Cycle 1 · None	15 Participants
Time to Onset of Treatment Effect Cycle 1 · Day 0	10 Participants
Time to Onset of Treatment Effect Cycle 1 · Day 1	86 Participants
Time to Onset of Treatment Effect Cycle 1 · Day 2	168 Participants
Time to Onset of Treatment Effect Cycle 1 · Day 3	171 Participants
Time to Onset of Treatment Effect Cycle 1 · Day 4	93 Participants
Time to Onset of Treatment Effect Cycle 1 · Day 5	75 Participants
Time to Onset of Treatment Effect Cycle 1 · Day 6	33 Participants
Time to Onset of Treatment Effect Cycle 1 · Day 7	70 Participants
Time to Onset of Treatment Effect Cycle 1 · Day 8	12 Participants
Time to Onset of Treatment Effect Cycle 1 · Day 9	5 Participants
Time to Onset of Treatment Effect Cycle 1 · Day >=10	48 Participants
Time to Onset of Treatment Effect Cycle 2 · None	20 Participants
Time to Onset of Treatment Effect Cycle 2 · Day 0	22 Participants
Time to Onset of Treatment Effect Cycle 2 · Day 1	106 Participants
Time to Onset of Treatment Effect Cycle 2 · Day 2	134 Participants
Time to Onset of Treatment Effect Cycle 2 · Day 3	138 Participants
Time to Onset of Treatment Effect Cycle 2 · Day 4	82 Participants
Time to Onset of Treatment Effect Cycle 2 · Day 5	53 Participants
Time to Onset of Treatment Effect Cycle 2 · Day 6	17 Participants
Time to Onset of Treatment Effect Cycle 2 · Day 7	58 Participants
Time to Onset of Treatment Effect Cycle 2 · Day 8	10 Participants
Time to Onset of Treatment Effect Cycle 2 · Day 9	9 Participants
Time to Onset of Treatment Effect Cycle 2 · Day >=10	41 Participants
Time to Onset of Treatment Effect Cycle 3 · None	6 Participants
Time to Onset of Treatment Effect Cycle 3 · Day 0	8 Participants
Time to Onset of Treatment Effect Cycle 3 · Day 1	44 Participants
Time to Onset of Treatment Effect Cycle 3 · Day 2	56 Participants
Time to Onset of Treatment Effect Cycle 3 · Day 3	70 Participants
Time to Onset of Treatment Effect Cycle 3 · Day 4	46 Participants
Time to Onset of Treatment Effect Cycle 3 · Day 5	36 Participants
Time to Onset of Treatment Effect Cycle 3 · Day 6	11 Participants
Time to Onset of Treatment Effect Cycle 3 · Day 7	18 Participants
Time to Onset of Treatment Effect Cycle 3 · Day 8	3 Participants
Time to Onset of Treatment Effect Cycle 3 · Day 9	6 Participants
Time to Onset of Treatment Effect Cycle 3 · Day >=10	15 Participants
Time to Onset of Treatment Effect Cycle 4 · None	4 Participants
Time to Onset of Treatment Effect Cycle 4 · Day 0	10 Participants
Time to Onset of Treatment Effect Cycle 4 · Day 1	39 Participants
Time to Onset of Treatment Effect Cycle 4 · Day 2	54 Participants
Time to Onset of Treatment Effect Cycle 4 · Day 3	78 Participants
Time to Onset of Treatment Effect Cycle 4 · Day 4	33 Participants
Time to Onset of Treatment Effect Cycle 4 · Day 5	29 Participants
Time to Onset of Treatment Effect Cycle 4 · Day 6	6 Participants
Time to Onset of Treatment Effect Cycle 4 · Day 7	22 Participants
Time to Onset of Treatment Effect Cycle 4 · Day 8	6 Participants
Time to Onset of Treatment Effect Cycle 4 · Day 9	6 Participants
Time to Onset of Treatment Effect Cycle 4 · Day >=10	18 Participants
Time to Onset of Treatment Effect Cycle 5 · None	6 Participants
Time to Onset of Treatment Effect Cycle 5 · Day 0	9 Participants
Time to Onset of Treatment Effect Cycle 5 · Day 1	37 Participants
Time to Onset of Treatment Effect Cycle 5 · Day 2	64 Participants
Time to Onset of Treatment Effect Cycle 5 · Day 3	57 Participants
Time to Onset of Treatment Effect Cycle 5 · Day 4	39 Participants
Time to Onset of Treatment Effect Cycle 5 · Day 5	21 Participants
Time to Onset of Treatment Effect Cycle 5 · Day 6	17 Participants
Time to Onset of Treatment Effect Cycle 5 · Day 7	20 Participants
Time to Onset of Treatment Effect Cycle 5 · Day 8	5 Participants
Time to Onset of Treatment Effect Cycle 5 · Day 9	4 Participants
Time to Onset of Treatment Effect Cycle 5 · Day >=10	11 Participants
Time to Onset of Treatment Effect Cycle 6 · None	2 Participants
Time to Onset of Treatment Effect Cycle 6 · Day 0	10 Participants
Time to Onset of Treatment Effect Cycle 6 · Day 1	33 Participants
Time to Onset of Treatment Effect Cycle 6 · Day 2	46 Participants
Time to Onset of Treatment Effect Cycle 6 · Day 3	56 Participants
Time to Onset of Treatment Effect Cycle 6 · Day 4	42 Participants
Time to Onset of Treatment Effect Cycle 6 · Day 5	20 Participants
Time to Onset of Treatment Effect Cycle 6 · Day 6	5 Participants
Time to Onset of Treatment Effect Cycle 6 · Day 7	21 Participants
Time to Onset of Treatment Effect Cycle 6 · Day 8	7 Participants
Time to Onset of Treatment Effect Cycle 6 · Day 9	2 Participants
Time to Onset of Treatment Effect Cycle 6 · Day >=10	15 Participants
Time to Onset of Treatment Effect Cycle 7 · None	3 Participants
Time to Onset of Treatment Effect Cycle 7 · Day 0	8 Participants
Time to Onset of Treatment Effect Cycle 7 · Day 1	17 Participants
Time to Onset of Treatment Effect Cycle 7 · Day 2	36 Participants
Time to Onset of Treatment Effect Cycle 7 · Day 3	43 Participants
Time to Onset of Treatment Effect Cycle 7 · Day 4	29 Participants
Time to Onset of Treatment Effect Cycle 7 · Day 5	19 Participants
Time to Onset of Treatment Effect Cycle 7 · Day 6	8 Participants
Time to Onset of Treatment Effect Cycle 7 · Day 7	15 Participants
Time to Onset of Treatment Effect Cycle 7 · Day 8	6 Participants
Time to Onset of Treatment Effect Cycle 7 · Day 9	1 Participants
Time to Onset of Treatment Effect Cycle 7 · Day >=10	5 Participants
Time to Onset of Treatment Effect Cycle 8 · None	0 Participants
Time to Onset of Treatment Effect Cycle 8 · Day 0	1 Participants
Time to Onset of Treatment Effect Cycle 8 · Day 1	6 Participants
Time to Onset of Treatment Effect Cycle 8 · Day 2	4 Participants
Time to Onset of Treatment Effect Cycle 8 · Day 3	17 Participants
Time to Onset of Treatment Effect Cycle 8 · Day 4	4 Participants
Time to Onset of Treatment Effect Cycle 8 · Day 5	7 Participants
Time to Onset of Treatment Effect Cycle 8 · Day 6	2 Participants
Time to Onset of Treatment Effect Cycle 8 · Day 7	4 Participants
Time to Onset of Treatment Effect Cycle 8 · Day 8	2 Participants
Time to Onset of Treatment Effect Cycle 8 · Day 9	0 Participants
Time to Onset of Treatment Effect Cycle 8 · Day >=10	1 Participants

Adverse Events

IncobotulinumtoxinA 20 U

Serious events: 29 serious events

Other events: 169 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	IncobotulinumtoxinA 20 U n=796 participants at risk Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length = 90 days.
Congenital, familial and genetic disorders Atrial septal defect	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Gastrointestinal disorders Anal fissure	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Gastrointestinal disorders Colonic polyp	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Gastrointestinal disorders Haemorrhoids	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Hepatobiliary disorders Bile duct stone	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Hepatobiliary disorders Cholelithiasis	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Infections and infestations Appendicitis	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Infections and infestations Herpes zoster oticus	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Injury, poisoning and procedural complications Joint dislocation	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Injury, poisoning and procedural complications Ligament rupture	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Injury, poisoning and procedural complications Radius fracture	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Injury, poisoning and procedural complications Tibia fracture	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.25% 2/796 • Number of events 2 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lipoma	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Salivary gland neoplasm	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Nervous system disorders Cerebrovascular accident	0.25% 2/796 • Number of events 2 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Nervous system disorders Cerebral artery embolism	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Nervous system disorders Cerebral infarction	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Nervous system disorders Facial paresis	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Nervous system disorders Migraine	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Pregnancy, puerperium and perinatal conditions Abortion missed	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Pregnancy, puerperium and perinatal conditions Blighted ovum	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Psychiatric disorders Suicide attempt	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Reproductive system and breast disorders Uterine polyp	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Reproductive system and breast disorders Uterine prolapse	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Surgical and medical procedures Hysterectomy	0.25% 2/796 • Number of events 2 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Surgical and medical procedures Mammoplasty	0.25% 2/796 • Number of events 2 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Surgical and medical procedures Cardiac operation	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Surgical and medical procedures Cholecystectomy	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Surgical and medical procedures Cystopexy	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Surgical and medical procedures Phlebectomy	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Surgical and medical procedures Polypectomy	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Surgical and medical procedures Removal of internal fixation	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Vascular disorders Arterial stenosis	0.13% 1/796 • Number of events 2 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Vascular disorders Haematoma	0.13% 1/796 • Number of events 1 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.

Other adverse events

Other adverse events
Measure	IncobotulinumtoxinA 20 U n=796 participants at risk Participants, pre-treated with placebo, and incobotulinumtoxinA (NT 201) 10, 20 and 30 U in feeder studies; received incobotulinumtoxinA 20 U powder for solution for injection, intramuscularly, in equal aliquots to 5 injection sites (Point A \[one injection in procerus muscle at crossing of two lines that connect Point B and contralateral caruncle\], Point B \[one injection on each side in central part of corrugator muscle approximately 1 cm above bony orbital rim on an imaginary line drawn vertically from caruncle\], and Point C \[one injection on each side in middle part of corrugator muscle at least 1.5 cm above bony orbital rim on an imaginary line drawn vertically from midpupillary line\]) on Day 0 of Cycle 1. Re-injections based on investigator assessment were performed on Day 0 of subsequent cycles (up to 8 cycles for participants enrolled from MRZ 60201-0520/1 and MRZ 60201-0527/1; and up to 2 cycles for participants enrolled from MRZ 60201-0724/1 and MRZ 60201-0741/1). Each cycle length = 90 days.
Infections and infestations Nasopharyngitis	13.7% 109/796 • Number of events 154 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.
Nervous system disorders Headache	7.5% 60/796 • Number of events 116 • Baseline up to Month 30 The investigator asked the participant for AEs systematically at each visit.

Additional Information

Public Disclosure Manager

Merz Pharmaceuticals GmbH

Phone: +49 69 1503 1

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER