A Safety and Efficacy Study of OnabotulinumtoxinA in Forehead and Glabellar Facial Rhytides

Evaluation of the Safety and Efficacy of Treatment With BOTOX® (Botulinum Toxin Type A) Purified Neurotoxin Complex for Subjects With Forehead and Glabellar Facial Rhytides

This is a safety and efficacy study of onabotulinumtoxinA in subjects with forehead and glabellar facial rhytides (frown lines).

Study Overview

• Status: Completed
• Conditions: Glabellar Rhytides; Forehead Rhytides
• Intervention / Treatment: Biological: OnabotulinumtoxinA; Drug: Normal Saline

• Study Type: Interventional
• Enrollment (Actual): 421
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E1
      • Dr. Shannon Humphrey, Inc.
    • Vancouver, British Columbia, Canada, V5Z 4E1
      • Carruthers Dermatology Centre
    • Vancouver, British Columbia, Canada, V5Z 4E1
      • Jean Carruthers Cosmetic Dermatology
  • Ontario
    • Toronto, Ontario, Canada, M5R 3N8
      • Sweat Clinics of Canada
  • Quebec
    • Westmount, Quebec, Canada, H3Z 1B7
      • Arthur Swift Research, Inc.
• Ireland
  • Dublin, Ireland
    • Aesthetic Surgery Ireland
  • Dublin, Ireland
    • Beacon Face and Dermatology Clinic
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Total Skin and Beauty Dermatology Center, PC
  • Arizona
    • Glendale, Arizona, United States, 85308
      • Advanced Research Associates
  • California
    • Santa Monica, California, United States, 90404
      • Clinical Science Institute
  • Colorado
    • Greenwood Village, Colorado, United States, 80111
      • About Skin Dermatology and DermSurgery, PC
  • Florida
    • Boca Raton, Florida, United States, 33431
      • Steven Fagien, MD, PA
  • Indiana
    • Carmel, Indiana, United States, 46032
      • Laser & Skin Surgery Center of Indiana
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Coleman Center For Cosmetic Dermatologic Surgery
  • Michigan
    • West Bloomfield, Michigan, United States, 48322
      • Henry Ford Medical Center
  • Oregon
    • Portland, Oregon, United States, 97210
      • NW Dermatology and Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Moderate to severe forehead and glabellar lines
• Willing to have facial photos taken

Exclusion Criteria:

• Prior exposure to botulinum toxin of any serotype for any indication
• Anticipated need for treatment with botulinum toxin of any serotype for any indication during the study, other than study treatment
• Diagnosis of myasthenia gravis, Eaton-Lambert syndrome, or amyotrophic lateral sclerosis
• Any facial resurfacing laser or light treatment, microdermabrasion, or superficial peels in the past 3 months
• Any medium depth or deep depth facial chemical peels; facial skin resurfacing; or permanent facial make-up in the past 6 months
• Any nonpermanent soft tissue fillers, or treatment with oral retinoids in the past year
• Prior face lift, thread lift, eyebrow lift, or related procedures (eg, eyelid and/or eyebrow surgery)
• Prior facial treatment with permanent soft tissue fillers, synthetic implants (eg, Gore-Tex®), and/or fat transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OnabotulinumtoxinA; OnabotulinumtoxinA injected into the protocol-specified areas on Day 1. Subjects will receive at least 1 and up to 3 treatments.	Biological: OnabotulinumtoxinA; OnabotulinumtoxinA injected into the protocol-specified areas. Subjects will receive at least 1 and up to 3 treatments.; Other Names: botulinum toxin Type A; BOTOX® Cosmetic
Placebo Comparator: Placebo followed by OnabotulinumtoxinA in Period 2; Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria in Period 2, the subject will receive up to 2 open-label treatments with onabotulinumtoxinA into the protocol-specified areas.	Drug: Normal Saline; Placebo (normal saline) injected into the protocol-specified areas on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With ≥2-Grade Improvement From Baseline on Both the Investigator's and Subject's Facial Wrinkle Scale (FWS) Ratings of Forehead Line Severity at Maximum Eyebrow Elevation	The Investigator and subject each assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 2-grade improvement from baseline assessed by both the Investigator and the subject are reported.	Baseline, Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With an Investigator Rating of None or Mild on the 4-Grade FWS for Forehead Line Severity at Maximum Eyebrow Elevation	The Investigator assessed the severity of the subject's forehead lines at maximum eyebrow elevation using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with a score of "none" and "mild" are reported.	Day 30
Percentage of Subjects With ≥1-Grade Improvement From Baseline on the Investigator's FWS Rating of Forehead Line Severity at Rest	The Investigator assessed the severity of the subject's forehead lines at rest using the 4-grade FWS, where 0=none, 1=mild, 2=moderate, and 3=severe. The percentage of subjects with at least a 1-grade improvement assessed by the Investigator are reported.	Baseline, Day 30
Percentage of Subjects Reporting Mostly Satisfied or Very Satisfied on the 5-Point Facial Line Satisfaction Questionnaire (FLSQ) Item 5	The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. Item 5 on the FLSQ asks "How satisfied are you with the effect your treatment had on your facial lines?" Responses included: very satisfied, mostly satisfied, neither satisfied or dissatisfied, mostly dissatisfied, or very dissatisfied. The percentage of subjects reporting a score of mostly satisfied or very satisfied with treatment are reported.	Day 60
Percentage of Subjects With ≥20-Point Improvement From Baseline on the Impact Domain of the FLSQ Among Subjects With Baseline Score ≥ 20 Points	The FLSQ consists of 13 questions that assess subject satisfaction and appearance-related impacts associated with facial lines. The Impact Domain measures the subject's appearance-related and emotional impacts of treatment and is composed of 5 questions with a possible range of scores from 0 (worst) to 100 (best), using a transformed scale. Only subjects with baseline scores ≥ 20 are included in the analysis.	Baseline, Day 30
Percentage of Subjects With a ≥3-Point Improvement From Baseline on Item 4 of the 11-Point Facial Line Outcomes (FLO-11) Questionnaire©	The FLO-11 assess the subject's psychological and appearance-related impacts associated with facial lines. Item 4 is "I look older than my actual age because of my facial lines" with a range of possible scores from 0 = not at all to 10 = very much. Only subjects with baseline scores ≥ 3 are included in the analysis.	Baseline, Day 30
Time to Retreatment Eligibility	Time to retreatment eligibility is defined as the number of days from treatment cycle 1 injection to the return to an Investigator FWS rating of moderate or severe at maximum eyebrow elevation. The FWS is a 4-grade scale, where 0=none, 1=mild, 2=moderate, and 3=severe. Only subjects who achieved a ≥ 2-grade improvement on both the Investigator and subject FWS ratings at maximum eyebrow elevation on Day 30 are included in the analysis.	12 Months

Collaborators and Investigators

• Sponsor: Allergan

Publications and helpful links

General Publications

• De Boulle K, Werschler WP, Gold MH, Bruce S, Sattler G, Ogilvie P, Street J, Larsen KE, Yushmanova I, Lei X, Lee E, Vitarella D, Mao C. Phase 3 Study of OnabotulinumtoxinA Distributed Between Frontalis, Glabellar Complex, and Lateral Canthal Areas for Treatment of Upper Facial Lines. Dermatol Surg. 2018 Nov;44(11):1437-1448. doi: 10.1097/DSS.0000000000001612.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2014
• Primary Completion (Actual): June 4, 2015
• Study Completion (Actual): April 26, 2016

Study Registration Dates

• First Submitted: October 3, 2014
• First Submitted That Met QC Criteria: October 7, 2014
• First Posted (Estimate): October 10, 2014

Study Record Updates

• Last Update Posted (Actual): January 8, 2019
• Last Update Submitted That Met QC Criteria: December 18, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: 191622-142; 2014-001860-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No