NCT01189747

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

Completed Phase 3 Results posted Last updated 7 May 2019

What this trial tests

Phase 3 trial testing onabotulinumtoxinA in Lateral Canthus Rhytides in 446 participants. Completed in 1 July 2011.

Timeline

1 October 2010

Primary endpoint
1 April 2011

1 July 2011

Quick facts

Lead sponsor	Allergan
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	446
Start date	1 October 2010
Primary completion	1 April 2011
Estimated completion	1 July 2011
Sites	4 locations across Belgium, United Kingdom, Canada, United States

Drugs / interventions tested

• onabotulinumtoxinA (ONABOTULINUMTOXINA) — full drug profile →
• normal saline

Conditions studied

• Lateral Canthus Rhytides — all drugs for Lateral Canthus Rhytides →
• Crow's Feet Lines — all drugs for Crow's Feet Lines →

Sponsor

Allergan — full company profile →

Who can join

18 and older, any sex, with Lateral Canthus Rhytides or Crow's Feet Lines. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Responders Based on Composite Facial Wrinkle Scale Assessment of Crow's Feet Line Severity at Maximum Smile Primary · Baseline, Day 30

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.

Group	Value	95% CI
onabotulinumtoxinA	25.7
Placebo (Normal Saline)	1.3

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 Secondary · 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. The percentage of participants with a score of none or mild at Day 30 is reported.

Group	Value	95% CI
onabotulinumtoxinA	66.7
Placebo (Normal Saline)	6.7

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 Secondary · Baseline, 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. The percentage of participants with a ≥ 1-grade improvement from Baseline at Day 30 is reported.

Group	Value	95% CI
onabotulinumtoxinA	87.4
Placebo (Normal Saline)	12.1

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 Secondary · Baseline, Day 30

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.

Group	Value	95% CI
onabotulinumtoxinA	67.3
Placebo (Normal Saline)	13.5

Subject Global Assessment of Change in Crow's Feet Lines (SGA-CFL) Score Secondary · Day 30

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.

Group	Value	95% CI
onabotulinumtoxinA	2.2	± 1.06
Placebo (Normal Saline)	3.8	± 0.67

Percentage of Participants Who Judged Themselves in a Younger Self-Perception of Age Category Than at Baseline Secondary · Baseline, Day 30

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.

Group	Value	95% CI
onabotulinumtoxinA	45.4
Placebo (Normal Saline)	10.8

Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 2 at Day 30 Secondary · Baseline, Day 30

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).

Group	Value	95% CI
onabotulinumtoxinA	70.0
Placebo (Normal Saline)	28.4

Percentage of Participants With a ≥ 2-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 5 at Day 30 Secondary · Baseline, Day 30

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).

Group	Value	95% CI
onabotulinumtoxinA	66.8
Placebo (Normal Saline)	22.8

Percentage of Participants With a ≥ 3-point Improvement From Baseline for Facial Line Outcomes Questionnaire (FLO-11) Item 8 at Day 30 Secondary · Baseline, Day 30

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).

Group	Value	95% CI
onabotulinumtoxinA	55.8
Placebo (Normal Saline)	16.3

Adverse events — posted to ClinicalTrials.gov

Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

onabotulinumtoxinA

Serious: 6/220 (3%)

Deaths: —

Placebo (Normal Saline)

Serious: 3/224 (1%)

Deaths: —

Serious adverse events (10 terms)

Reaction	System	onabotulinumtoxinA	Placebo (Normal Saline)
Coronary artery disease	Cardiac disorders	—	—
Myocardial infarction	Cardiac disorders	—	—
Cholangitis	Hepatobiliary disorders	—	—
Bursitis infective	Infections and infestations	—	—
Invertebral disc disorder	Musculoskeletal and connective tissue disorders	—	—
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Intraductal papilloma of breast	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Abortion	Pregnancy, puerperium and perinatal conditions	—	—
Femoral artery occlusion	Vascular disorders	—	—

Most-reported serious reactions: Coronary artery disease, Myocardial infarction, Cholangitis, Bursitis infective, Invertebral disc disorder, Basal cell carcinoma, Breast cancer, Intraductal papilloma of breast.

Data from ClinicalTrials.gov NCT01189747 adverse events section.

Sponsor's own description

This study will evaluate the safety and efficacy of botulinum toxin Type A compared to placebo for the treatment of Crow's Feet Lines (Lateral Canthal Rhytides).

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Neurotoxin Impurities: A Review of Threats to Efficacy.
   Park JY, Sunga O, Wanitphakdeedecha R, Frevert J. · · 2020 · cited 27× · PMID 32095419 · DOI 10.1097/gox.0000000000002627
2. Botulinum toxin type A for facial wrinkles.
   Camargo CP, Xia J, Costa CS, Gemperli R, et al · · 2021 · cited 21× · PMID 34224576 · DOI 10.1002/14651858.cd011301.pub2