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Clinical Trial Results:
A Phase 3, Multicenter Study to Evaluate the Safety and Efficacy of AGN-151586 for the Treatment of Glabellar Lines

Summary
EudraCT number	2021-003667-10
Trial protocol	HU
Global end of trial date	17 Mar 2023

Results information
Results version number	v1(current)
This version publication date	27 Mar 2024
First version publication date	27 Mar 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

M21-500

ISRCTN number

US NCT number

NCT05248867

WHO universal trial number (UTN)

Sponsor organisation name

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation address

AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB

Public contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com

Scientific contact

Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

17 Mar 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

17 Mar 2023

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study was to evaluate the safety and efficacy of AGN-151586 for the treatment of glabellar lines (GL) in participants with moderate to severe GL. This was a 12-week study in which eligible subjects were enrolled into the study containing 2 treatment periods, double-blind period and open-label period. Participants were randomly assigned to receive AGN-151586 or placebo. Participants received either AGN-151586 or Placebo administered as 5 intramuscular injections to the glabellar complex on Day 1. Participants meeting retreatment criteria may have received an open-label treatment of AGN-151586 during the study.

Protection of trial subjects

Subjects signed and dated an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Mar 2022

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Canada: 64

Country: Number of subjects enrolled

Germany: 59

Country: Number of subjects enrolled

Hungary: 40

Country: Number of subjects enrolled

Poland: 41

Country: Number of subjects enrolled

United States: 434

Worldwide total number of subjects

638

EEA total number of subjects

140

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

586

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Subjects who didn’t meet eligibility criteria were allowed to be rescreened. Rescreening only occurred after discussion with the Sponsor. Rescreening could only occur once for any given potential subject; however, if the original screen failure was due to ineligible Frown Wrinkle Scale (FWS) grade(s), the subject was not permitted to rescreen.

Period 1 title

Double-blind period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received 5 intramuscular injections of placebo in the glabellar complex on Day 1. Based on meeting the retreatment criteria, the participants may have also received 1 open-label treatment of AGN-151586 on Day 43.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Placebo solution for injection

AGN-151586

Arm description

Participants received 5 intramuscular injections of AGN-151586 in the glabellar complex on Day 1. Based on meeting the retreatment criteria, participants may also have received 1 open-label treatment of AGN-151586 on Day 43.

Arm type

Experimental

Investigational medicinal product name

AGN-151586

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

AGN-151586 solution for injection

Number of subjects in period 1	Placebo	AGN-151586
Started	156	482
Completed	148	454
Not completed	8	28
Other, not specified	3	8
Lost to follow-up	-	3
Withdrawal by subject due to adverse event	-	3
Withdrawal by subject	5	14

Period 2 title

Open-label period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo/None

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

Placebo/AGN-151586

Arm description

Participants received placebo injections during the Double-blind Period and met all the retreatment criteria on Day 43. A single open-label treatment with AGN-151586 was administered on Day 43. Participants were followed for approximately 6 weeks (through Day 84).

Arm type

Experimental

Investigational medicinal product name

AGN-151586

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

AGN-151586 solution for injection

AGN-151586/None

Arm description

Arm type

No intervention

Investigational medicinal product name

No investigational medicinal product assigned in this arm

AGN-151586/AGN-151586

Arm description

Participants received AGN-151586 during the Double-blind Period and met all the retreatment criteria on Day 43. An additional open-label treatment with AGN-151586 was administered on Day 43. Participants were followed for approximately 6 weeks (through Day 84).

Arm type

Experimental

Investigational medicinal product name

AGN-151586

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

AGN-151586 solution for injection

Number of subjects in period 2	Placebo/None	Placebo/AGN-151586	AGN-151586/None	AGN-151586/AGN-151586
Started	3	145	17	437
Completed	0	143	0	426
Not completed	3	2	17	11
Other, not specified	-	-	4	-
Lost to follow-up	-	-	5	2
Withdrawal by subject due to adverse event	-	1	-	-
COVID-19 infection	-	-	1	-
Withdrawal by subject	3	1	7	9

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Reporting group title

AGN-151586

Reporting group description

Reporting group values	Placebo	AGN-151586	Total
Number of subjects	156	482	638
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	47.6 ± 12.48	47.1 ± 12.75	-
Gender categorical
Units: Subjects
Female	137	429	566
Male	19	53	72
Ethnicity
Units: Subjects
Hispanic or Latino	14	49	63
Not Hispanic or Latino	142	433	575
Unknown or Not Reported	0	0	0
Race
Units: Subjects
American Indian or Alaska Native	1	0	1
Asian	3	16	19
Native Hawaiian or Other Pacific Islander	2	2	4
Black or African American	5	21	26
White	142	432	574
More than one race	3	11	14
Unknown or Not Reported	0	0	0
Facial Wrinkle Scale (FWS) at Maximum Frown - Participant
Participants' assessment of the severity of glabellar lines (GL) at maximum frown was performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity.
Units: Subjects
0 = None	0	0	0
1 = Mild	1	3	4
2 = Moderate	41	149	190
3 = Severe	114	330	444
Facial Wrinkle Scale (FWS) at Maximum Frown - Investigator
Investigators' assessment of the severity of glabellar lines (GL) at maximum frown was performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity.
Units: Subjects
0 = None	0	0	0
1 = Mild	1	2	3
2 = Moderate	41	149	190
3 = Severe	114	331	445

End points

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Reporting group title

Placebo

Reporting group description

Reporting group title

AGN-151586

Reporting group description

Reporting group title

Placebo/None

Reporting group description

Reporting group title

Placebo/AGN-151586

Reporting group description

Reporting group title

AGN-151586/None

Reporting group description

Reporting group title

AGN-151586/AGN-151586

Reporting group description

Primary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Both Investigator and Subject Assessments of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [US FDA]

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End point title

Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Both Investigator and Subject Assessments of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [US FDA]

End point description

[Primary endpoint for the United States FDA] Percentage of participants achieving a Grade 0 or 1 (none or mild) and a ≥2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to both investigator and participant assessments of glabellar lines (GL) severity at maximum frown at Day 7 are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis population: Intent-to-Treat (ITT) population: all randomized participants, analyzed according to the treatment groups to which they were randomized. Multiple imputation was used for missing data.

End point type

Primary

End point timeframe

Baseline, Day 7 (Double-blind period)

End point values	Placebo	AGN-151586
Number of subjects analysed	156	482
Units: percentage of participants
number (confidence interval 95%)	0.6 (0.0 to 1.9)	60.0 (55.5 to 64.4)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

638

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[1]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

59.3

Confidence interval

level

95%

sides

2-sided

lower limit

54.7

upper limit

63.9

Notes
[1] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Primary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [European Union Regulatory Agencies]

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End point title

Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [European Union Regulatory Agencies]

End point description

[Primary endpoint for European Union regulatory agencies] Percentage of participants with a ≥2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to participant assessment of glabellar lines (GL) severity at maximum frown at Day 7 are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Primary

End point timeframe

Baseline, Day 7 (Double-blind period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)	0.8 (0.0 to 2.3)	61.0 (55.9 to 66.0)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[2]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

60.2

Confidence interval

level

95%

sides

2-sided

lower limit

54.9

upper limit

65.4

Notes
[2] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Primary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [European Union Regulatory Agencies]

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End point title

Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [European Union Regulatory Agencies]

End point description

[Primary endpoint for European Union regulatory agencies] Percentage of participants with a ≥2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to investigator assessment of glabellar lines (GL) severity at maximum frown at Day 7 are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Primary

End point timeframe

Baseline, Day 7 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)	0.8 (0.0 to 2.3)	72.1 (67.5 to 76.7)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[3]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

71.4

Confidence interval

level

95%

sides

2-sided

lower limit

66.5

upper limit

76.2

Notes
[3] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Primary: Number of Participants With Adverse Events

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End point title

Number of Participants With Adverse Events ^[4]

End point description

An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug.

End point type

Primary

End point timeframe

From Day 1 to Day 43 (Double-blind Period) and from Day 43 to Day 84 (Open-label Period)

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive data are summarized for this end point per protocol.

End point values	Placebo	AGN-151586	Placebo/None	Placebo/AGN-151586	AGN-151586/None	AGN-151586/AGN-151586
Number of subjects analysed	156 ^[5]	482 ^[6]	0 ^[7]	145 ^[8]	0 ^[9]	437 ^[10]
Units: participants
Any TEAE (n=156, 482, 0, 145, 0, 437)	44	118		32		90
TESAE (n=156, 482, 0, 145, 0, 437)	1	3		0		1

Notes
[5] - Subjects treated with ≥ 1 dose of study drug, analyzed by actual Tx received
[6] - Subjects treated with ≥ 1 dose of study drug, analyzed by actual Tx received
[7] - Subjects didn’t receive Tx during Open-label Period/weren’t analyzed for TEAEs during OL Period
[8] - Subjects treated with ≥ 1 dose of study drug, analyzed by actual Tx received
[9] - Subjects didn’t receive Tx during Open-label Period/weren’t analyzed for TEAEs during OL Period
[10] - Subjects treated with ≥ 1 dose of study drug, analyzed by actual Tx received

No statistical analyses for this end point

Secondary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Both Investigator and Participant Assessments of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

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End point title

Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Both Investigator and Participant Assessments of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

End point description

[Secondary endpoint for the United States FDA] Percentage of participants achieving a Grade 0 or 1 (none or mild) and a ≥2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to both investigator and participant assessments of glabellar lines (GL) severity at maximum frown over time are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Hours 8, 12, 24, 36, and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	156	482
Units: percentage of participants
number (confidence interval 95%)
Hour 8	0.0 (0.0 to 0.0)	7.1 (4.8 to 9.3)
Hour 12	0.6 (0.0 to 1.9)	15.9 (12.6 to 19.2)
Hour 24	0.6 (0.0 to 1.9)	30.4 (26.3 to 34.6)
Hour 36	0.6 (0.0 to 1.9)	43.2 (38.7 to 47.6)
Hour 48	0.6 (0.0 to 1.9)	50.1 (45.6 to 54.6)
Day 7	0.6 (0.0 to 1.9)	60.0 (55.5 to 64.4)
Day 14	0.0 (0.0 to 0.0)	25.3 (21.4 to 29.2)
Day 21	0.0 (0.0 to 0.0)	2.7 (1.3 to 4.2)
Day 28	0.0 (0.0 to 0.0)	0.2 (0.0 to 0.6)
Day 35	0.0 (0.0 to 0.0)	0.4 (0.0 to 1.0)
Day 43	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

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End point title

Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

End point description

[Secondary endpoint for the United States FDA] Percentage of participants with a Grade 0 or 1 (none or mild) and at least a 2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to investigator assessment of glabellar lines (GL) severity at maximum frown over time are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Hours 8, 12, 24, 36, and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	156	482
Units: percentage of participants
number (confidence interval 95%)
Hour 8	1.3 (0.0 to 3.0)	11.0 (8.2 to 13.8)
Hour 12	0.7 (0.0 to 2.0)	20.2 (16.6 to 23.8)
Hour 24	0.6 (0.0 to 1.9)	37.4 (33.1 to 41.8)
Hour 36	0.7 (0.0 to 2.0)	53.1 (48.6 to 57.6)
Hour 48	0.6 (0.0 to 1.9)	62.2 (57.9 to 66.6)
Day 7	0.6 (0.0 to 1.9)	72.6 (68.6 to 76.6)
Day 14	0.0 (0.0 to 0.0)	32.3 (28.1 to 36.6)
Day 21	0.0 (0.0 to 0.0)	5.2 (3.2 to 7.3)
Day 28	0.0 (0.0 to 0.0)	1.3 (0.3 to 2.2)
Day 35	0.0 (0.0 to 0.0)	0.4 (0.0 to 1.0)
Day 43	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)

No statistical analyses for this end point

Secondary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

Top of page

End point title

Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

End point description

[Secondary endpoint for the United States FDA] Percentage of participants with a Grade 0 or 1 (none or mild) and at least a 2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to participant assessment of glabellar lines (GL) severity at maximum frown over time are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Hours 8, 12, 24, 36, and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	156	482
Units: percentage of participants
number (confidence interval 95%)
Hour 8	0.0 (0.0 to 0.0)	8.1 (5.7 to 10.5)
Hour 12	0.7 (0.0 to 2.0)	18.5 (15.0 to 22.0)
Hour 24	0.6 (0.0 to 1.9)	32.1 (27.9 to 36.3)
Hour 36	0.6 (0.0 to 1.9)	44.4 (40.0 to 48.9)
Hour 48	1.9 (0.0 to 4.1)	51.8 (47.3 to 56.3)
Day 7	0.6 (0.0 to 1.9)	63.3 (58.9 to 67.6)
Day 14	0.0 (0.0 to 0.0)	29.8 (25.6 to 34.0)
Day 21	0.0 (0.0 to 0.0)	4.2 (2.4 to 6.1)
Day 28	0.0 (0.0 to 0.0)	1.9 (0.7 to 3.1)
Day 35	1.3 (0.0 to 3.0)	1.2 (0.3 to 2.2)
Day 43	0.0 (0.0 to 0.0)	0.8 (0.0 to 1.7)

No statistical analyses for this end point

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Day 7 [US FDA]

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End point title

Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Day 7 [US FDA]

End point description

[Secondary endpoint for the United States FDA] The FLSQ is a validated measure that assesses treatment expectations, treatment satisfaction, and psychosocial impact of GL from the participant perspective. Participants assessed their overall satisfaction with their glabellar lines using a 5-point verbal descriptor scale (VDS): very dissatisfied, mostly dissatisfied, neither dissatisfied nor satisfied, mostly satisfied, and very satisfied. The percentage of participants mostly satisfied or very satisfied is reported. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Day 7 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	156	482
Units: percentage of participants
number (confidence interval 95%)	5.1 (1.7 to 8.6)	77.6 (73.9 to 81.4)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

638

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[11]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

72.5

Confidence interval

level

95%

sides

2-sided

lower limit

67.4

upper limit

77.6

Notes
[11] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Hour 24 [United States FDA]

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End point title

End point description

End point type

Secondary

End point timeframe

Hour 24 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	156	482
Units: percentage of participants
number (confidence interval 95%)	17.3 (11.4 to 23.2)	59.2 (54.8 to 63.6)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

638

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[12]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

41.9

Confidence interval

level

95%

sides

2-sided

lower limit

34.5

upper limit

49.3

Notes
[12] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 4 (Natural Look) for GL at Day 7 [US FDA]

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End point title

Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 4 (Natural Look) for GL at Day 7 [US FDA]

End point description

[Secondary endpoint for the United States FDA] The FLSQ is a validated measure that assesses treatment expectations, treatment satisfaction, and psychosocial impact of GL from the participant perspective. Participants assessed their satisfaction with natural look using a 5-point verbal descriptor scale (VDS): very dissatisfied, mostly dissatisfied, neither dissatisfied nor satisfied, mostly satisfied, and very satisfied. The percentage of participants mostly satisfied or very satisfied is reported. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Day 7 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	156	482
Units: percentage of participants
number (confidence interval 95%)	9.0 (4.5 to 13.5)	78.5 (74.8 to 82.2)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

638

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[13]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

69.5

Confidence interval

level

95%

sides

2-sided

lower limit

63.7

upper limit

75.3

Notes
[13] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Percentage of Participants With a ≥20-point Improvement From Baseline in FLO-11 Total Scores for GL at Day 7 [European Union Regulatory Agencies]

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End point title

Percentage of Participants With a ≥20-point Improvement From Baseline in FLO-11 Total Scores for GL at Day 7 [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] The Facial Lines Outcomes (FLO-11) Questionnaire is an 11-item validated measure that assesses appearance-related psychological impacts of glabellar lines (GL) from the participant’s perspective. Items 1-10 are assessed on an 11-point numeric rating scale that ranges from 0 (Not at all) to 10 (Very much), with higher scores indicating negative impact. Item 11 is scored in the reverse direction. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50 were included. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Day 7 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)	8.5 (3.7 to 13.2)	66.6 (61.8 to 71.5)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[14]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

58.2

Confidence interval

level

95%

sides

2-sided

lower limit

51.3

upper limit

Notes
[14] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Top of page

End point title

Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] Percentage of participants with a ≥2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to participant assessment of glabellar lines (GL) severity at maximum frown at Hour 24 are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Hour 24 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)	0.8 (0.0 to 2.3)	30.9 (26.2 to 35.7)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[15]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

30.1

Confidence interval

level

95%

sides

2-sided

lower limit

25.2

upper limit

35.1

Notes
[15] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Top of page

End point title

Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] Percentage of participants with a ≥2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to investigator assessment of glabellar lines (GL) severity at maximum frown at Hour 24 during the Double-Blind Period are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Hour 24 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)	0.8 (0.0 to 2.3)	36.5 (31.5 to 41.4)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[16]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

35.7

Confidence interval

level

95%

sides

2-sided

lower limit

30.5

upper limit

40.9

Notes
[16] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Percentage of Participants With a ≥1-grade Improvement From Baseline on FWS According to Participant Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Top of page

End point title

Percentage of Participants With a ≥1-grade Improvement From Baseline on FWS According to Participant Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] Percentage of participants with a ≥1-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to participant assessment of glabellar lines (GL) severity at maximum frown at Hour 24 are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Hour 24 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)	11.5 (6.0 to 17.0)	64.1 (59.2 to 69.1)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[17]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

52.6

Confidence interval

level

95%

sides

2-sided

lower limit

45.2

upper limit

Notes
[17] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Percentage of Participants With a ≥1-grade Improvement From Baseline on FWS According to Investigator Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Top of page

End point title

Percentage of Participants With a ≥1-grade Improvement From Baseline on FWS According to Investigator Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] Percentage of participants with a ≥1-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to investigator assessment of glabellar lines (GL) severity at maximum frown at Hour 24 are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Hour 24 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)	13.8 (7.9 to 19.8)	72.5 (67.9 to 77.1)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[18]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

58.6

Confidence interval

level

95%

sides

2-sided

lower limit

51.1

upper limit

66.1

Notes
[18] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Hour 24 [European Union Regulatory Agencies]

Top of page

End point title

End point description

[Secondary endpoint for European Union regulatory agencies] The FLSQ is a validated measure that assesses treatment expectations, treatment satisfaction, and psychosocial impact of GL from the participant perspective. Participants assessed their overall satisfaction with their glabellar lines using a 5-point verbal descriptor scale (VDS): very dissatisfied, mostly dissatisfied, neither dissatisfied nor satisfied, mostly satisfied, and very satisfied. The percentage of participants mostly satisfied or very satisfied is reported. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Hour 24 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)	16.2 (9.8 to 22.5)	58.7 (53.6 to 63.7)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[19]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

42.5

Confidence interval

level

95%

sides

2-sided

lower limit

34.4

upper limit

50.6

Notes
[19] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 4 (Natural Look) for GL at Day 7 [European Union Regulatory Agencies]

Top of page

End point title

End point description

[Secondary endpoint for European Union regulatory agencies] The FLSQ is a validated measure that assesses treatment expectations, treatment satisfaction, and psychosocial impact of GL from the participant perspective. Participants assessed their satisfaction with natural look using a 5-point verbal descriptor scale (VDS): very dissatisfied, mostly dissatisfied, neither dissatisfied nor satisfied, mostly satisfied, and very satisfied. The percentage of participants mostly satisfied or very satisfied is reported. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Day 7 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)	7.7 (3.1 to 12.3)	77.7 (73.3 to 82.0)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

498

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[20]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

63.7

upper limit

76.3

Notes
[20] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Time to the First ≥1-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown [European Union Regulatory Agencies]

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End point title

Time to the First ≥1-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] Time to the first ≥1-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to participant assessment of glabellar lines (GL) severity at maximum frown is reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. For those who did not improve at least 1 grade from Baseline, censoring occurred at the latest visit during the treatment period for which FWS data were available. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50.

End point type

Secondary

End point timeframe

From Baseline to Day 43 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: days
median (full range (min-max))	41.9 (0 to 69)	1.0 (0 to 45)

No statistical analyses for this end point

Secondary: Time to the First ≥1-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown [European Union Regulatory Agencies]

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End point title

Time to the First ≥1-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] Time to the first ≥1-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to investigator assessment of glabellar lines (GL) severity at maximum frown is reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. For those who did not improve at least 1 grade from Baseline, censoring occurred at the latest visit during the treatment period for which FWS data were available. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50.

End point type

Secondary

End point timeframe

From Baseline to Day 43 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: days
median (full range (min-max))	41.0 (0 to 69)	0.7 (0 to 45)

No statistical analyses for this end point

Secondary: Percentage of Participants With ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown Over Time [European Union Regulatory Agencies]

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End point title

Percentage of Participants With ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown Over Time [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] Percentage of participants with at least a 2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to participant assessment of glabellar lines (GL) severity at maximum frown over time are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Hours 8, 12, 24, 36, and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)
Hour 8	0.0 (0.0 to 0.0)	7.6 (4.9 to 10.3)
Hour 12	0.8 (0.0 to 2.3)	17.7 (13.8 to 21.7)
Hour 24	0.8 (0.0 to 2.3)	30.9 (26.2 to 35.7)
Hour 36	0.8 (0.0 to 2.3)	44.0 (38.9 to 49.1)
Hour 48	2.3 (0.0 to 4.9)	50.1 (45.0 to 55.3)
Day 7	0.8 (0.0 to 2.3)	61.0 (55.9 to 66.0)
Day 14	0.0 (0.0 to 0.0)	30.5 (25.6 to 35.3)
Day 21	0.0 (0.0 to 0.0)	4.6 (2.4 to 6.9)
Day 28	0.0 (0.0 to 0.0)	1.9 (0.5 to 3.3)
Day 35	1.5 (0.0 to 3.7)	1.4 (0.2 to 2.5)
Day 43	0.0 (0.0 to 0.0)	0.8 (0.0 to 1.8)

No statistical analyses for this end point

Secondary: Percentage of Participants With ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown Over Time [European Union Regulatory Agencies]

Top of page

End point title

Percentage of Participants With ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown Over Time [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] Percentage of participants with at least a 2-grade improvement from Baseline on the Facial Wrinkle Scale (FWS) according to investigator assessment of glabellar lines (GL) severity at maximum frown over time are reported. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Hours 8, 12, 24, 36, and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)
Hour 8	1.5 (0.0 to 3.7)	10.9 (7.7 to 14.1)
Hour 12	0.8 (0.0 to 2.3)	18.6 (14.5 to 22.6)
Hour 24	0.8 (0.0 to 2.3)	36.5 (31.5 to 41.4)
Hour 36	0.8 (0.0 to 2.3)	53.3 (48.1 to 58.4)
Hour 48	0.8 (0.0 to 2.3)	61.7 (56.6 to 66.7)
Day 7	0.8 (0.0 to 2.3)	72.1 (67.5 to 76.7)
Day 14	0.0 (0.0 to 0.0)	32.8 (27.9 to 37.7)
Day 21	0.0 (0.0 to 0.0)	5.4 (3.0 to 7.7)
Day 28	0.0 (0.0 to 0.0)	1.1 (0.0 to 2.2)
Day 35	0.0 (0.0 to 0.0)	0.3 (0.0 to 0.8)
Day 43	0.0 (0.0 to 0.0)	0.0 (0.0 to 0.0)

No statistical analyses for this end point

Secondary: Time to Return to Baseline FWS According to Participant Assessment of FWS at Maximum Frown After Achieving Responder Definition on Day 7 [European Union Regulatory Agencies]

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End point title

Time to Return to Baseline FWS According to Participant Assessment of FWS at Maximum Frown After Achieving Responder Definition on Day 7 [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] Time to return to Baseline (Baseline criterion of Moderate or Severe) on the Facial Wrinkle Scale (FWS) according to participant assessment of FWS at maximum frown after achieving responder definition on Day 7 is reported. Responder definition was a rating of None or Mild on the FWS. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. For those who maintained their response, censoring occurred at the latest visit during the treatment period for which FWS was available. Analysis Population: Intent-to-Treat (ITT) Population: all randomized subjects, analyzed according treatment groups to which they were randomized with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Those who didn't meet responder definition on Day 7 were excluded from analysis; analysis was limited to those that responded.

End point type

Secondary

End point timeframe

From Baseline to Day 43 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	3	251
Units: days
median (full range (min-max))	28.0 (15 to 43)	21.0 (8 to 50)

No statistical analyses for this end point

Secondary: Time to Return to Baseline FWS According to Investigator Assessment of FWS at Maximum Frown After Achieving Responder Definition on Day 7 [European Union Regulatory Agencies]

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End point title

Time to Return to Baseline FWS According to Investigator Assessment of FWS at Maximum Frown After Achieving Responder Definition on Day 7 [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] Time to return to Baseline (Baseline criterion of Moderate or Severe) on the Facial Wrinkle Scale (FWS) according to investigator assessment of FWS at maximum frown after achieving responder definition on Day 7 is reported. Responder definition was a rating of None or Mild on the FWS. Assessments were performed using the 4-grade Facial Wrinkle Scale (FWS), where 0=none, 1=mild, 2=moderate, and 3=severe. Higher scores indicate more severity. For those who maintained their response, censoring occurred at the latest visit during the treatment period for which FWS was available. Analysis Population: Intent-to-Treat (ITT) Population: all randomized subjects, analyzed according treatment groups to which they were randomized with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Those who didn't meet responder definition on Day 7 were excluded from analysis; analysis was limited to those who responded.

End point type

Secondary

End point timeframe

From Baseline to Day 43 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	2	280
Units: days
median (full range (min-max))	15.0 (15 to 15)	21.0 (8 to 50)

No statistical analyses for this end point

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL Over Time [European Union Regulatory Agencies]

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End point title

End point description

End point type

Secondary

End point timeframe

Baseline, Hours 8, 24, and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: percentage of participants
number (confidence interval 95%)
Hour 8	14.3 (8.2 to 20.4)	33.1 (28.3 to 38.0)
Hour 24	16.2 (9.8 to 22.5)	58.7 (53.6 to 63.7)
Hour 48	8.5 (3.7 to 13.2)	71.4 (66.7 to 76.0)
Day 7	4.6 (1.0 to 8.3)	76.9 (72.5 to 81.2)
Day 14	5.8 (1.7 to 10.0)	69.9 (65.1 to 74.7)
Day 21	2.5 (0.0 to 5.2)	61.4 (56.3 to 66.5)
Day 28	4.7 (0.9 to 8.4)	56.1 (50.9 to 61.2)
Day 35	3.8 (0.5 to 7.2)	58.3 (53.2 to 63.4)
Day 43	4.8 (1.1 to 8.6)	58.1 (52.9 to 63.4)

No statistical analyses for this end point

Secondary: Percentage of Participants With a ≥4-point Improvement From Baseline in FLO-11 Item 10 (Look Angry) for GL at Day 7 [European Union Regulatory Agencies]

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End point title

Percentage of Participants With a ≥4-point Improvement From Baseline in FLO-11 Item 10 (Look Angry) for GL at Day 7 [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] The Facial Lines Outcomes (FLO-11) Questionnaire is an 11-item validated measure that assesses appearance-related psychological impacts of glabellar lines (GL) from the participant’s perspective. Items 1-10 are assessed on an 11-point numeric rating scale that ranges from 0 (Not at all) to 10 (Very much), with higher scores indicating negative impact. Item 11 is scored in the reverse direction. Participants answered FLO-11 Item 10 (Look Angry). Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, and a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Participants with a score that could improve at least 4 points from Baseline were included. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Day 7 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	124	353
Units: percentage of participants
number (confidence interval 95%)	5.6 (1.6 to 9.7)	54.5 (49.2 to 59.7)

AGN-151586 vs Placebo

Comparison groups

Placebo v AGN-151586

Number of subjects included in analysis

477

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[21]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

48.8

Confidence interval

level

95%

sides

2-sided

lower limit

42.2

upper limit

55.4

Notes
[21] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Percentage of Participants With a ≥4-point Improvement From Baseline in FLO-11 Item 5 (Look Less Attractive) for GL at Day 7 [European Union Regulatory Agencies]

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End point title

Percentage of Participants With a ≥4-point Improvement From Baseline in FLO-11 Item 5 (Look Less Attractive) for GL at Day 7 [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] The Facial Lines Outcomes (FLO-11) Questionnaire is an 11-item validated measure that assesses appearance-related psychological impacts of glabellar lines (GL) from the participant’s perspective. Items 1-10 are assessed on an 11-point numeric rating scale that ranges from 0 (Not at all) to 10 (Very much), with higher scores indicating negative impact. Item 11 is scored in the reverse direction. Participants answered FLO-11 Item 5 (Look Less Attractive). Percentages are rounded off to nearest single decimal. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, and a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Participants with a score that could improve at least 4 points from Baseline were included. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Baseline, Day 7 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	128	362
Units: percentage of participants
number (confidence interval 95%)	3.9 (0.5 to 7.3)	48.1 (42.9 to 53.3)

AGN-151586 vs Placebo

Comparison groups

AGN-151586 v Placebo

Number of subjects included in analysis

490

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[22]

Method

Cochran-Mantel-Haenszel

Parameter type

Rate difference

Point estimate

44.2

Confidence interval

level

95%

sides

2-sided

lower limit

upper limit

50.4

Notes
[22] - P-value was based on Cochran-Mantel-Haenszel (CMH) test stratified by investigator site, toxin use history (for aesthetic purposes), and baseline Facial Wrinkle Scale score at maximum frown after using multiple imputation for missing data.

Secondary: Mean Global Assessment of Change in Glabellar Lines (GAC-GL) at Maximum Frown Over Time [European Union Regulatory Agencies]

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End point title

Mean Global Assessment of Change in Glabellar Lines (GAC-GL) at Maximum Frown Over Time [European Union Regulatory Agencies]

End point description

[Secondary endpoint for European Union regulatory agencies] The GAC-GL Questionnaire assesses the appearance of the participant’s GL "now”in comparison with their perspective before treatment. Participants assessed the change in their glabellar lines at maximum frown using a 7-point verbal descriptor scale (VDS): very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse. Higher scores indicate more improvement. Analysis Population: Intent-to-Treat (ITT) Population: all randomized participants, analyzed according to the treatment groups to which they were randomized, with a Baseline Facial Lines Outcome (FLO-11) total score (transformed) of ≤50. Multiple imputation was used for missing data.

End point type

Secondary

End point timeframe

Hours 24 and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind Period)

End point values	Placebo	AGN-151586
Number of subjects analysed	130	368
Units: units on a scale
least squares mean (standard error)
Hour 24	0.2 ± 0.10	1.4 ± 0.07
Hour 48	0.1 ± 0.09	1.9 ± 0.06
Day 7	0.1 ± 0.08	2.2 ± 0.06
Day 14	0.1 ± 0.10	1.5 ± 0.07
Day 21	0.1 ± 0.10	0.5 ± 0.07
Day 28	0.1 ± 0.10	0.2 ± 0.07
Day 35	0.1 ± 0.10	0.0 ± 0.07
Day 43	0.1 ± 0.09	0.0 ± 0.06

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All-cause mortality reported from enrollment to study end; median time on follow-up was 85 days for Placebo, AGN-151586, Placebo/AGN-151586, and AGN-151586/AGN-151586 groups; 50 days for Placebo/None group; and 53 days for the AGN-151586/None group.

Adverse event reporting additional description

TEAEs/SAEs collected Day 1-43 (Double-blind Period) + Day 43-84 (Open-label Period) for those who rcvd Tx. Open-label Period Placebo/None and AGN-151586/None groups didn’t receive Tx during Open-label Period and therefore weren’t analyzed for TEAEs during that Period. TEAEs experienced by these subjects were recorded during Double-blind Period.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

Placebo

Reporting group description

Reporting group title

AGN-151586

Reporting group description

Reporting group title

AGN-151586/None

Reporting group description

Participants received AGN-151586 during the Double-blind Period but did not meet all the retreatment criteria on Day 43. Participants were followed weekly in the Open-label Period until the Facial Wrinkle Scale (FWS) grades assessed by both investigator and participant returned to moderate or severe (investigator and participant grades did not need to match) before being discontinued from the study after completing either the Early Exit or Study Exit Visit. Participants in the Open-label Period AGN-151586/None group did not receive treatment during the Open-label Period and therefore were not analyzed for treatment-emergent adverse events during the Open-label period. TEAEs experienced by these participants were recorded during the Double-blind Period

Reporting group title

Placebo/AGN-151586

Reporting group description

Reporting group title

AGN-151586/AGN-151586

Reporting group description

Reporting group title

Placebo/None

Reporting group description

Participants received placebo injections during the Double-blind Period but did not meet all the retreatment criteria on Day 43. Participants were followed weekly in the Open-label Period until the Facial Wrinkle Scale (FWS) grades assessed by both investigator and participant returned to moderate or severe (investigator and participant grades did not need to match) before being discontinued from the study after completing either the Early Exit or Study Exit Visit. Participants in the Open-label Period Placebo/None group did not receive treatment during the Open-label Period and therefore were not analyzed for treatment-emergent adverse events during the Open-label period. TEAEs experienced by these participants were recorded during the Double-blind Period.

Serious adverse events	Placebo	AGN-151586	AGN-151586/None	Placebo/AGN-151586	AGN-151586/AGN-151586	Placebo/None
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 156 (0.64%)	3 / 482 (0.62%)	0 / 17 (0.00%)	0 / 145 (0.00%)	1 / 437 (0.23%)	0 / 3 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
INVASIVE DUCTAL BREAST CARCINOMA
subjects affected / exposed	1 / 156 (0.64%)	0 / 482 (0.00%)	0 / 17 (0.00%)	0 / 145 (0.00%)	0 / 437 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
APPENDICITIS
subjects affected / exposed	0 / 156 (0.00%)	1 / 482 (0.21%)	0 / 17 (0.00%)	0 / 145 (0.00%)	0 / 437 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PNEUMONIA
subjects affected / exposed	0 / 156 (0.00%)	1 / 482 (0.21%)	0 / 17 (0.00%)	0 / 145 (0.00%)	0 / 437 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
PYELONEPHRITIS
subjects affected / exposed	0 / 156 (0.00%)	0 / 482 (0.00%)	0 / 17 (0.00%)	0 / 145 (0.00%)	1 / 437 (0.23%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
HYPOCALCAEMIA
subjects affected / exposed	0 / 156 (0.00%)	1 / 482 (0.21%)	0 / 17 (0.00%)	0 / 145 (0.00%)	0 / 437 (0.00%)	0 / 3 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Placebo	AGN-151586	AGN-151586/None	Placebo/AGN-151586	AGN-151586/AGN-151586	Placebo/None
Total subjects affected by non serious adverse events
subjects affected / exposed	9 / 156 (5.77%)	31 / 482 (6.43%)	0 / 17 (0.00%)	8 / 145 (5.52%)	14 / 437 (3.20%)	0 / 3 (0.00%)
Nervous system disorders
HEADACHE
subjects affected / exposed	9 / 156 (5.77%)	31 / 482 (6.43%)	0 / 17 (0.00%)	8 / 145 (5.52%)	14 / 437 (3.20%)	0 / 3 (0.00%)
occurrences all number	10	35	0	8	16	0

More information

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Were there any global substantial amendments to the protocol? Yes

01 Aug 2022

Protocol amendment 2 • Added FLSQ Item 5 at Day 7 as the third secondary endpoint • Planned balanced enrollment between moderate and severe GL severity at maximum frown • Added information re: no anticipated additional risk to subjects with use of AGN-151586 with regard to COVID-19; added information regarding anticipated risks with the use of AGN-151586 and provided overall benefit:risk conclusion • Indicated that specified endpoints will be evaluated outside of gated hierarchical testing; added estimand for FLSQ Item 5 at Day 7 • Clarified when visits will occur relative to treatment • Updated eligibility criteria to exclude those with personal/family history of prolonged QT; with clinically significant abnormal vital sign value at screening or Baseline Day 1 visit, removed specification of serum/urine pregnancy tests; semi-permanent make-up (e.g., microblading) not permitted in the 6-month period before Baseline Day 1 visit • Noted that at least 10 days must elapse since first COVID-19 positive test in asymptomatic subjects or at least 10 days since recovery • Added additional safety retreatment criteria, including no ongoing AEs that may place subject at increased risk following exposure to AGN-151586 and no clinically significant abnormality in safety assessments at retreatment visit • Updated COVID-19 language including recommendation that study drug be given ± 7 days from SARS-CoV-2 vaccine administration; added statement that any prior toxin therapy for aesthetics or therapeutic treatment at any time and COVID-19 vaccination history must be recorded • Clarified that subjects who are missing assessments or data due to COVID-19 pandemic and are missing data for the primary endpoints will count as though they hypothetically continued in the study • Added as-observed sensitivity analysis and NRI sensitivity analysis • Updated study start and end definition • Revised abbreviated physical exam on Day 7 (including retreatment Day 7) to a full exam

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Phase 3, Multicenter Study to Evaluate the Safety and Efficacy of AGN-151586 for the Treatment of Glabellar Lines

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Both Investigator and Subject Assessments of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [US FDA]

Primary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Both Investigator and Subject Assessments of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [US FDA]

Primary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [European Union Regulatory Agencies]

Primary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [European Union Regulatory Agencies]

Primary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [European Union Regulatory Agencies]

Primary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of Glabellar Lines (GL) Severity at Maximum Frown at Day 7 [European Union Regulatory Agencies]

Primary: Number of Participants With Adverse Events

Primary: Number of Participants With Adverse Events

Secondary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Both Investigator and Participant Assessments of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

Secondary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Both Investigator and Participant Assessments of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

Secondary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

Secondary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

Secondary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

Secondary: Percentage of Participants With a Grade 0 or 1 and a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of Glabellar Lines (GL) Severity at Maximum Frown Over Time [US FDA]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Day 7 [US FDA]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Day 7 [US FDA]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Hour 24 [United States FDA]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Hour 24 [United States FDA]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 4 (Natural Look) for GL at Day 7 [US FDA]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 4 (Natural Look) for GL at Day 7 [US FDA]

Secondary: Percentage of Participants With a ≥20-point Improvement From Baseline in FLO-11 Total Scores for GL at Day 7 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥20-point Improvement From Baseline in FLO-11 Total Scores for GL at Day 7 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥1-grade Improvement From Baseline on FWS According to Participant Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥1-grade Improvement From Baseline on FWS According to Participant Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥1-grade Improvement From Baseline on FWS According to Investigator Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥1-grade Improvement From Baseline on FWS According to Investigator Assessment of GL Severity at Maximum Frown at Hour 24 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Hour 24 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL at Hour 24 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 4 (Natural Look) for GL at Day 7 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 4 (Natural Look) for GL at Day 7 [European Union Regulatory Agencies]

Secondary: Time to the First ≥1-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown [European Union Regulatory Agencies]

Secondary: Time to the First ≥1-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown [European Union Regulatory Agencies]

Secondary: Time to the First ≥1-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown [European Union Regulatory Agencies]

Secondary: Time to the First ≥1-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown [European Union Regulatory Agencies]

Secondary: Percentage of Participants With ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown Over Time [European Union Regulatory Agencies]

Secondary: Percentage of Participants With ≥2-grade Improvement From Baseline on the FWS According to Participant Assessment of GL Severity at Maximum Frown Over Time [European Union Regulatory Agencies]

Secondary: Percentage of Participants With ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown Over Time [European Union Regulatory Agencies]

Secondary: Percentage of Participants With ≥2-grade Improvement From Baseline on the FWS According to Investigator Assessment of GL Severity at Maximum Frown Over Time [European Union Regulatory Agencies]

Secondary: Time to Return to Baseline FWS According to Participant Assessment of FWS at Maximum Frown After Achieving Responder Definition on Day 7 [European Union Regulatory Agencies]

Secondary: Time to Return to Baseline FWS According to Participant Assessment of FWS at Maximum Frown After Achieving Responder Definition on Day 7 [European Union Regulatory Agencies]

Secondary: Time to Return to Baseline FWS According to Investigator Assessment of FWS at Maximum Frown After Achieving Responder Definition on Day 7 [European Union Regulatory Agencies]

Secondary: Time to Return to Baseline FWS According to Investigator Assessment of FWS at Maximum Frown After Achieving Responder Definition on Day 7 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL Over Time [European Union Regulatory Agencies]

Secondary: Percentage of Participants With Achievement of Mostly Satisfied or Very Satisfied on the Facial Lines Satisfaction Questionnaire (FLSQ) Follow-up Version Item 5 (Overall Satisfaction) for GL Over Time [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥4-point Improvement From Baseline in FLO-11 Item 10 (Look Angry) for GL at Day 7 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥4-point Improvement From Baseline in FLO-11 Item 10 (Look Angry) for GL at Day 7 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥4-point Improvement From Baseline in FLO-11 Item 5 (Look Less Attractive) for GL at Day 7 [European Union Regulatory Agencies]

Secondary: Percentage of Participants With a ≥4-point Improvement From Baseline in FLO-11 Item 5 (Look Less Attractive) for GL at Day 7 [European Union Regulatory Agencies]

Secondary: Mean Global Assessment of Change in Glabellar Lines (GAC-GL) at Maximum Frown Over Time [European Union Regulatory Agencies]

Secondary: Mean Global Assessment of Change in Glabellar Lines (GAC-GL) at Maximum Frown Over Time [European Union Regulatory Agencies]

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 3, Multicenter Study to Evaluate the Safety and Efficacy of AGN-151586 for the Treatment of Glabellar Lines