Trial Outcomes & Findings for Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Crow's Feet Lines (NCT NCT01189747)

Results Overview

The composite facial wrinkle scale assessment is based on both the Investigator and Subject Facial Wrinkle scales at Day 30. The Investigator assessed the severity of the patient's Crow's Feet Lines at maximum smile using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe and the patient assessed the severity of their Crow's Feet Lines at maximum smile using the same 4-point Facial Wrinkle Scale. A responder is defined as a participant with a ≥ 2-grade improvement from Baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

446 participants

Primary outcome timeframe

Baseline, Day 30

Results posted on

2019-05-07

Participant Flow

Participant milestones

Participant milestones
Measure	onabotulinumtoxinA 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Overall Study STARTED	222	224
Overall Study COMPLETED	210	206
Overall Study NOT COMPLETED	12	18

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy Study of Botulinum Toxin Type A for the Treatment of Crow's Feet Lines

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	onabotulinumtoxinA n=222 Participants 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=224 Participants normal saline injected into bilateral Crow's Feet Line areas on Day 1.	Total n=446 Participants Total of all reporting groups
Age, Customized < 45 Years	82 Participants n=5 Participants	101 Participants n=7 Participants	183 Participants n=5 Participants
Age, Customized 45 to 65 Years	135 Participants n=5 Participants	118 Participants n=7 Participants	253 Participants n=5 Participants
Age, Customized > 65 Years	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Female	193 Participants n=5 Participants	192 Participants n=7 Participants	385 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	32 Participants n=7 Participants	61 Participants n=5 Participants
CFL Severity as Assessed by Investigator Moderate	109 Participants n=5 Participants	112 Participants n=7 Participants	221 Participants n=5 Participants
CFL Severity as Assessed by Investigator Severe	112 Participants n=5 Participants	111 Participants n=7 Participants	223 Participants n=5 Participants
CFL Severity as Assessed by Investigator No data available	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-treat population included all randomized participants. Participants with missing values are considered non-responders.

The composite facial wrinkle scale assessment is based on both the Investigator and Subject Facial Wrinkle scales at Day 30. The Investigator assessed the severity of the patient's Crow's Feet Lines at maximum smile using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe and the patient assessed the severity of their Crow's Feet Lines at maximum smile using the same 4-point Facial Wrinkle Scale. A responder is defined as a participant with a ≥ 2-grade improvement from Baseline.

Outcome measures

Outcome measures
Measure	onabotulinumtoxinA n=222 Participants 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=223 Participants normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Percentage of Responders Based on Composite Facial Wrinkle Scale Assessment of Crow's Feet Line Severity at Maximum Smile	25.7 Percentage of participants	1.3 Percentage of participants

SECONDARY outcome

Timeframe: Day 30

Population: Intent-to-treat population included all randomized participants.

The Investigator assessed the severity of the patient's Crow's Feet lines at maximum smile using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe. The percentage of participants with a score of none or mild at Day 30 is reported.

Outcome measures

Outcome measures
Measure	onabotulinumtoxinA n=222 Participants 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=223 Participants normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Percentage of Participants Achieving a Grade of None or Mild at Maximum Smile Based on the Investigator's Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines	66.7 Percentage of participants	6.7 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-treat population included all randomized participants.

The Investigator assessed the severity of the patient's Crow's Feet Lines at maximum smile using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe. The percentage of participants with a ≥ 1-grade improvement from Baseline at Day 30 is reported.

Outcome measures

Outcome measures
Measure	onabotulinumtoxinA n=222 Participants 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=223 Participants normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Maximum Smile	87.4 Percentage of participants	12.1 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-treat participants included all randomized participants. Only participants who were rated at least mild at Baseline are included in the analyses.

The Investigator assessed the severity of the patient's Crow's Feet Lines at rest using the 4-point Facial Wrinkle Scale: 0=none, 1=mild, 2=moderate or 3=severe. The percentage of participants with a ≥ 1-grade improvement from Baseline at Day 30 is reported.

Outcome measures

Outcome measures
Measure	onabotulinumtoxinA n=214 Participants 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=215 Participants normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Percentage of Participants With a ≥ 1-Grade Improvement From Baseline by Investigator Facial Wrinkle Scale Assessment of the Severity of Crow's Feet Lines at Rest	67.3 Percentage of participants	13.5 Percentage of participants

SECONDARY outcome

Timeframe: Day 30

Population: Intent-to-treat population included all randomized participants.

Patients rated the change in their Crow's Feet Lines using the SGA-CFL 7-point scale: 1=very much improved, 2=much improved, 3=minimally improved, 4=no change, 5=minimally worse, 6=much worse or 7=very much worse at Day 30. Lower scores indicate improvement.

Outcome measures

Outcome measures
Measure	onabotulinumtoxinA n=222 Participants 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=223 Participants normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Subject Global Assessment of Change in Crow's Feet Lines (SGA-CFL) Score	2.2 Score on a scale Standard Deviation 1.06	3.8 Score on a scale Standard Deviation 0.67

SECONDARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-treat population included all randomized participants. Only those participants who rated themselves as "look my current age" or "look older" at Baseline are included in the analyses.

Participants were considered to judge themselves younger if the category change was from "look my current age" at Baseline to "look younger" at Day 30 or from "look older" at Baseline to "look my current age/younger" at Day 30.

Outcome measures

Outcome measures
Measure	onabotulinumtoxinA n=183 Participants 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=185 Participants normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Percentage of Participants Who Judged Themselves in a Younger Self-Perception of Age Category Than at Baseline	45.4 Percentage of participants	10.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-treat population consisted of all randomized participants. Only subjects with Baseline scores ≥ 2 were included.

The percentage of FLO-11 Item #2 responders, defined as participants with a ≥ 2-point improvement in FLO-11 score from Baseline for FLO-11 Question #2: "When I look in the mirror, my facial lines make me look older than I want to look." The FLO-11 questionnaire is comprised of 11 items that assess the subject's perceptions about specific aspects of their facial lines for the previous 7 days. Each question is scored on an 11-point scale (0=not at all, 5=somewhat, 10=very much).

Outcome measures

Outcome measures
Measure	onabotulinumtoxinA n=213 Participants 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=211 Participants normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 2 at Day 30	70.0 Percentage of participants	28.4 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-treat population consisted of all randomized participants. Only subjects with Baseline scores ≥ 2 were included.

The percentage of FLO-11 Item #5 responders, defined as participants with a ≥ 2-point improvement in FLO-11 score from Baseline for FLO-11 Question #5: "My facial lines make me look less attractive than I want to look." The FLO-11 questionnaire is comprised of 11 items that assess the subject's perceptions about specific aspects of their facial lines for the previous 7 days. Each question is scored on an 11-point scale (0=not at all, 5=somewhat, 10=very much).

Outcome measures

Outcome measures
Measure	onabotulinumtoxinA n=202 Participants 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=202 Participants normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 5 at Day 30	66.8 Percentage of participants	22.8 Percentage of participants

SECONDARY outcome

Timeframe: Baseline, Day 30

Population: Intent-to-treat population consisted of all randomized participants. Only subjects with Baseline scores ≥ 3 were included.

The percentage of FLO-11 Item #8 responders, defined as participants with a ≥ 3-point improvement in FLO-11 score from baseline for FLO-11 Question #8: "My facial lines make me look tired" The FLO-11 questionnaire is comprised of 11 items that assess the subject's perceptions about specific aspects of their facial lines for the previous 7 days. Each question is scored on an 11-point scale (0=not at all, 5=somewhat, 10=very much).

Outcome measures

Outcome measures
Measure	onabotulinumtoxinA n=199 Participants 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=203 Participants normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Percentage of Participants With a ≥ 3-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 8 at Day 30	55.8 Percentage of participants	16.3 Percentage of participants

Adverse Events

onabotulinumtoxinA

Serious events: 6 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo (Normal Saline)

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	onabotulinumtoxinA n=220 participants at risk 24 units onabotulinumtoxinA (botulinum toxin Type A) total dose injected into bilateral Crow's Feet Line areas on Day 1.	Placebo (Normal Saline) n=224 participants at risk normal saline injected into bilateral Crow's Feet Line areas on Day 1.
Cardiac disorders Coronary artery disease	0.45% 1/220 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.	0.00% 0/224 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Cardiac disorders Myocardial infarction	0.45% 1/220 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.	0.00% 0/224 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Hepatobiliary disorders Cholangitis	0.45% 1/220 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.	0.00% 0/224 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Infections and infestations Bursitis infective	0.45% 1/220 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.	0.00% 0/224 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Musculoskeletal and connective tissue disorders Invertebral disc disorder	0.00% 0/220 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.	0.45% 1/224 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.45% 1/220 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.	0.00% 0/224 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.45% 1/220 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.	0.00% 0/224 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal papilloma of breast	0.00% 0/220 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.	0.45% 1/224 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Pregnancy, puerperium and perinatal conditions Abortion	0.45% 1/220 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.	0.00% 0/224 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.
Vascular disorders Femoral artery occlusion	0.00% 0/220 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.	0.45% 1/224 The safety population (all treated participants) was used to calculate the number of participants at risk for Serious Adverse Events and Adverse Events.

Other adverse events

Adverse event data not reported

Additional Information

Therapeutic Area Head,

Allergan, Inc

Phone: 714-246-4500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Publication restrictions are in place

Restriction type: OTHER