A Safety and Efficacy Study of OnabotulinumtoxinA in Upper Facial Rhytides

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

This is a safety and efficacy study of onabotulinumtoxinA in subjects with upper facial rhytides (forehead lines, glabellar lines, lateral canthal lines [crow's feet lines]).

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 787
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium
    • Aalst Dermatology Clinic
  • Jette, Belgium
    • UZ Brussel
  • Limburg, Belgium
    • Medical Skin Care - Sint-Truiden
• Germany
  • Darmstadt, Germany
    • Rosenpark Research
  • Köln Nordrhein-Westfalen, Germany
    • Hautzentrum Koeln (Cologne Dermatology)
  • München, Germany
    • Hautok und hautok-cosmetics
  • München, Germany
    • Praxisgemeinschaft Theatiner46
  • Starnberg, Germany
    • Hautzentrum am Starnberger See GmbH
  • Wuppertal, Germany
    • CentroDerm Study Center
• United Kingdom
  • Basingstoke, United Kingdom, RG24 9DT
    • Shakespeare House Health Centre, General Practice
  • Birmingham, United Kingdom, B74 2UG
    • Medizen Clinic
  • Chichester, United Kingdom, PO18 8AN
    • The Bosham Clinic
  • Coatbridge, United Kingdom, ML5 3PA
    • Waverlery Medical Practice
  • Whitegate, United Kingdom, CW9 8UW
    • The Gatehouse
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • The Petrus Center for Aesthetic
  • California
    • Los Angeles, California, United States, 90025
      • Westside Aesthetics
    • Newport Beach, California, United States, 92663
      • Eye Research Foundation
    • Newport Beach, California, United States, 92663
      • Steve Yoelin, MD Medical Associates, Inc.
  • Florida
    • Miami, Florida, United States, 33137
      • Baumann Cosmetic & Research Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63122
      • Saint Louis University
  • New York
    • Mount Kisco, New York, United States, 10549
      • The Center for Dermatology Cosmetic and Laser Surgery
  • Tennessee
    • Nashville, Tennessee, United States, 37215
      • Tennessee Clinical Research Center
  • Texas
    • Houston, Texas, United States, 77056
      • The Center for Skin Research
  • Washington
    • Spokane, Washington, United States, 99202
      • Premier Clinical Research

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 lines, glabellar lines, and crow's feet 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OnabotulinumtoxinA Dose A; OnabotulinumtoxinA Dose A 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
Experimental: OnabotulinumtoxinA Dose B; OnabotulinumtoxinA Dose B 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 Dose A; Placebo (normal saline) injected into the protocol-specified areas on Day 1. If the subject meets the re-treatment criteria, the subject will receive up to 2 treatments with onabotulinumtoxinA Dose A 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

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2014
• Primary Completion (Actual): June 3, 2015
• Study Completion (Actual): April 20, 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): July 25, 2017
• Last Update Submitted That Met QC Criteria: June 26, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Facies; 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: 191622-143; 2014-001815-38 (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