Clinical Trial Results:
A Phase 3, Multicenter Study to Evaluate the Safety and Efficacy of AGN-151586 for the Treatment of Glabellar Lines
Summary
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EudraCT number |
2021-003667-10 |
Trial protocol |
HU |
Global end of trial date |
17 Mar 2023
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Results information
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Results version number |
v1 |
This version publication date |
27 Mar 2024
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First version publication date |
27 Mar 2024
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
M21-500
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05248867 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
AbbVie Deutschland GmbH & Co. KG
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Sponsor organisation address |
AbbVie House, Vanwall Business Park, Vanwall Road, Maidenhead, Berkshire, United Kingdom, SL6-4UB
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Public contact |
Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
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Scientific contact |
Global Medical Services, AbbVie, 001 8006339110, abbvieclinicaltrials@abbvie.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Mar 2023
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Mar 2023
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Was the trial ended prematurely? |
No
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General information about the trial
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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.
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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.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
16 Mar 2022
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Canada: 64
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Country: Number of subjects enrolled |
Germany: 59
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Country: Number of subjects enrolled |
Hungary: 40
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Country: Number of subjects enrolled |
Poland: 41
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Country: Number of subjects enrolled |
United States: 434
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Worldwide total number of subjects |
638
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EEA total number of subjects |
140
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
586
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From 65 to 84 years |
52
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85 years and over |
0
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Recruitment
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Recruitment details |
- | |||||||||||||||||||||||||||||||||||||||||||||
Pre-assignment
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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
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Period 1 title |
Double-blind period
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Assessor | |||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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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
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Placebo solution for injection
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Arm title
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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
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
AGN-151586 solution for injection
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Period 2
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Period 2 title |
Open-label period
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Is this the baseline period? |
No | |||||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | |||||||||||||||||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo/None | |||||||||||||||||||||||||||||||||||||||||||||
Arm 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. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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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
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
AGN-151586 solution for injection
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Arm title
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AGN-151586/None | |||||||||||||||||||||||||||||||||||||||||||||
Arm 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. | |||||||||||||||||||||||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Arm title
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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
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
AGN-151586 solution for injection
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
AGN-151586
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Reporting group 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group 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. | ||
Reporting group title |
AGN-151586
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Reporting group 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. | ||
Reporting group title |
Placebo/None
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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. | ||
Reporting group title |
Placebo/AGN-151586
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Reporting group 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). | ||
Reporting group title |
AGN-151586/None
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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. | ||
Reporting group title |
AGN-151586/AGN-151586
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Reporting group 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). |
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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.
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End point type |
Primary
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End point timeframe |
Baseline, Day 7 (Double-blind period)
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Statistical analysis title |
AGN-151586 vs Placebo | ||||||||||||
Comparison groups |
Placebo v AGN-151586
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Number of subjects included in analysis |
638
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [1] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Rate difference | ||||||||||||
Point estimate |
59.3
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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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. |
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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.
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End point type |
Primary
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End point timeframe |
Baseline, Day 7 (Double-blind period)
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Statistical analysis title |
AGN-151586 vs Placebo | ||||||||||||
Comparison groups |
Placebo v AGN-151586
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Number of subjects included in analysis |
498
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [2] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Rate difference | ||||||||||||
Point estimate |
60.2
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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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. |
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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.
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End point type |
Primary
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End point timeframe |
Baseline, Day 7 (Double-blind Period)
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Statistical analysis title |
AGN-151586 vs Placebo | ||||||||||||
Comparison groups |
Placebo v AGN-151586
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Number of subjects included in analysis |
498
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.0001 [3] | ||||||||||||
Method |
Cochran-Mantel-Haenszel | ||||||||||||
Parameter type |
Rate difference | ||||||||||||
Point estimate |
71.4
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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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. |
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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.
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End point type |
Primary
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End point timeframe |
From Day 1 to Day 43 (Double-blind Period) and from Day 43 to Day 84 (Open-label Period)
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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. |
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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 |
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No statistical analyses for this end point |
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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)
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
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)
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
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)
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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. |
|
|||||||||||||
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 Hour 24 [United States 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 |
Hour 24 (Double-blind Period)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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. |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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. |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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 |
65 | ||||||||||||
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. |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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. |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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. |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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 |
60 | ||||||||||||
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. |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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. |
|
|||||||||||||
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 Hour 24 [European Union Regulatory Agencies] | ||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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. |
|
|||||||||||||
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 [European Union Regulatory Agencies] | ||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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 |
70
|
||||||||||||
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. |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
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)
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||||||||
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)
|
|||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||||||||||||||
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 Over Time [European Union Regulatory Agencies] | |||||||||||||||||||||||||||||||||||||||
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 |
Baseline, Hours 8, 24, and 48, Days 7, 14, 21, 28, 35, and 43 (Double-blind Period)
|
|||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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. |
|
|||||||||||||
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)
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
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 |
38 | ||||||||||||
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. |
|
|||||||||||||||||||||||||||||||||||||
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)
|
||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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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.
|
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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.
|
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
25.1
|
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Reporting groups
|
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Reporting group title |
Placebo
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
AGN-151586
|
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Reporting group 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
AGN-151586/None
|
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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
|
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Reporting group 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). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
AGN-151586/AGN-151586
|
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Reporting group 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). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo/None
|
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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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
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 |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |