Duration of Botox Using OLD Versus COLD for Treatment of Glabellar Lines

A Randomized, Parallel-Group Study on the Duration Response of Highly Concentrated On Label Dose (COLD) of BOTOX® Compared to the On Label Dose and Concentration (OLD) in Subjects With Moderate to Severe Dynamic Glabellar Lines

This is a blinded, randomized study in the US to compare the duration response of two different concentrations of BOTOX in healthy female subjects with moderate to severe dynamic glabellar lines on maximum frown.

Study Overview

• Status: Recruiting
• Conditions: Glabellar Frown Lines
• Intervention / Treatment: Drug: OnabotulinumtoxinA

Detailed Description

This study involves a blinded, randomized, parallel-group design. The aim of this study is to evaluate the duration response of BOTOX in subjects with moderate to severe dynamic glabellar lines at the approved on-label dose of 20 U, however comparing the use of highly Concentrated On Label Dose (COLD) to the On Label Dose and concentration (OLD). The COLD concentration is defined as 4 Units per 0.02 mL and the OLD concentration is defined as 4 Units per 0.1 mL.

The total BOTOX dose will be 20U divided into 5 injections for both study groups. However, the injection volume will differ for the two study groups, such that the OLD (4 U per 0.1 mL) group will receive a total of 0.5 mL and the COLD (4 U per 0.02 mL) group will receive a total of 0.1mL.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Encino, California, United States, 91436
      • Recruiting
      • Clinical Testing of Beverly Hills
      • Principal Investigator: John Joseph, MD
      • Sub-Investigator: Allen Foulad, MD
    • Newport Beach, California, United States, 92663
      • Recruiting
      • Steve Yoelin MD
      • Contact: Steve Yoelin, MD; Phone Number: 747-998-5160
      • Principal Investigator: Steve Yoelin, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• At least 18 years of age at the time of signing the informed consent.
• Overtly healthy as determined by medical evaluation (includes: medical history, physical examination, and vital signs).
• Subjects have moderate or severe dynamic glabellar lines on maximum frown as assessed with the Facial Wrinkle Scale.
• Female sex.
• Female subjects willing to minimize the risk of inducing pregnancy for the duration of the clinical study and follow-up period. A female subject is eligible to participate if she is not pregnant (has a negative urine pregnancy result at Day 1 prior to treatment), is not breastfeeding, and at least one of the following conditions applies: 1) not a female of childbearing potential or 2) a female of childbearing potential who agrees to follow the contraceptive guidance.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form.
• Written informed consent from the subject has been obtained prior to any study-related procedures.
• Written documentation has been obtained in accordance with the relevant country and local privacy requirements, where applicable (eg, Written Authorization for Use and Release of Health and Research Study Information)
• Able, as assessed by the blinded evaluating investigator, and willing to follow study instructions and likely to complete all required study visits

Exclusion Criteria:

• Brow or eyelid ptosis, excessive dermatochalasis, deep dermal scarring, thick sebaceous skin, or an inability to substantially lessen upper facial rhytids, even by physically spreading them apart.
• Facial asymmetry including, in the opinion of the investigator, significant asymmetry with active contraction or at rest of the frontalis muscle.
• Medical condition that may increase the subject's risk of exposure to botulinum toxin, including diagnosed myasthenia gravis, Lambert-Eaton Syndrome, amyotrophic lateral sclerosis, or any other disease that might interfere with neuromuscular function.
• Profound atrophy/excessive weakness of muscles in target areas of injection.
• History of facial nerve palsy.
• Infection at the injection site or systemic infection.
• Presence of inflammation at the proposed injection site.
• Previous cosmetic surgery to the upper face (eg, periorbital surgery, brow lift, eyelid or eyebrow surgery), tissue grafting, or tissue augmentation with silicone or fat or other permanent fillers, or planning a facial cosmetic procedure during the study period.
• Subjects have been treated in the upper face (forehead lines, glabellar lines, crow's feet lines) within 1 year prior to the Baseline/Day 1 Visit with botulinum toxin therapy of any serotype.
• Noncompliance with the proper washout periods for prohibited medications/procedures.
• Subjects on topical retinoid therapy and/or topical hormone cream applied to the face, who have not been on a consistent dose regimen for at least 6 months prior to enrollment and who are unable to maintain a consistent dose regimen during the study.
• Oral retinoid therapy within 1 year prior to study enrollment.
• Current enrollment in an investigational drug or device study or participation in such a study within 30 days of entry into this study.
• Females who are pregnant, breastfeeding, or planning a pregnancy during the study.
• Females of childbearing potential not using a reliable means of contraception.
• Known allergy or sensitivity to the study treatment or its components.
• Known immunization or hypersensitivity to any botulinum toxin serotype.
• Prior exposure to or anticipated need for treatment with botulinum toxin of any serotype for any reason during the study (other than study treatment).
• Evidence of recent alcohol or drug abuse.
• The subject has a condition or is in a situation which, in the investigator's opinion, may put the subject at significant risk, may confound the study results, or may interfere significantly with the subject's participation in the study.

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
Active Comparator: OLD (4 U per 0.1 mL); The total BOTOX dose will be 20U divided into 5 injections. Each injection will receive a total of 0.5 mL.	Drug: OnabotulinumtoxinA; Injection of glabellar rhytids; Other Names: Botox
Active Comparator: COLD (4 U per 0.02 mL group); The total BOTOX dose will be 20U divided into 5 injections. Each injection will receive a total of 0.1 mL.	Drug: OnabotulinumtoxinA; Injection of glabellar rhytids; Other Names: Botox

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Duration	Time to return to baseline Facial Wrinkle Scale (FWS) score at maximum frown, as assessed by the blinded evaluating investigator. The Facial Wrinkle Scale (FWS) scale ranges from a score of 0 to 3, and a higher score indicates greater (more severe) glabellar wrinkles.	180 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Investigator Live Assessment (Dynamic)	Responder rate at each visit on the Facial Wrinkle Scale (FWS) at maximum frown, as assessed by the blinded evaluating investigator. The responder rate is defined as the proportion of subjects maintaining a greater than or equal to 1 point improvement on the FWS. The Facial Wrinkle Scale (FWS) scale ranges from a score of 0 to 3, and a higher score indicates greater (more severe) glabellar wrinkles.	180 days
Subject Self Assessment (Dynamic)	Responder rate at each visit on the Facial Wrinkles Scale (FWS) at maximum frown, as assessed by the subject. The Facial Wrinkle Scale (FWS) scale ranges from a score of 0 to 3, and a higher score indicates greater (more severe) glabellar wrinkles.	180 days
Investigator Live Assessment (At Rest)	Responder rate at each visit on the Facial Wrinkle Scale (FWS) at rest, as assessed by the blinded evaluating investigator. The Facial Wrinkle Scale (FWS) scale ranges from a score of 0 to 3, and a higher score indicates greater (more severe) glabellar wrinkles.	180 days
Subject Self Assessment (At Rest)	Responder rate at each visit on the Facial Wrinkle Scale (FWS) at rest, as assessed by the subject. The Facial Wrinkle Scale (FWS) scale ranges from a score of 0 to 3, and a higher score indicates greater (more severe) glabellar wrinkles.	180 days
Change from Baseline Score	Change from baseline in mean Facial Wrinkle Scale (FWS) score at maximum frown, as assessed by the blinded evaluating investigator, at each visit. The Facial Wrinkle Scale (FWS) scale ranges from a score of 0 to 3, and a higher score indicates greater (more severe) glabellar wrinkles.	180 days
Change in Frontalis Function	Percentage of subjects with weakening of frontalis muscle function using the Frontalis Function Scale (FFS) compared to baseline, as assessed by the blinded evaluating investigator, at each visit. The Frontalis Function Scale (FFS) scale ranges from a score of 0 to 3, and a higher score indicates greater reduction of forehead movement during maximal brow raise.	180 days

Collaborators and Investigators

• Sponsor: Clinical Testing of Beverly Hills
• Collaborators: Allergan

Publications and helpful links

General Publications

• Blitzer A, Binder WJ, Aviv JE, Keen MS, Brin MF. The management of hyperfunctional facial lines with botulinum toxin. A collaborative study of 210 injection sites in 162 patients. Arch Otolaryngol Head Neck Surg. 1997 Apr;123(4):389-92. doi: 10.1001/archoto.123.4.389.
• Carruthers A, Carruthers J, Said S. Dose-ranging study of botulinum toxin type A in the treatment of glabellar rhytids in females. Dermatol Surg. 2005 Apr;31(4):414-22; discussion 422. doi: 10.1111/j.1524-4725.2005.31107.
• Carruthers JA, Lowe NJ, Menter MA, Gibson J, Nordquist M, Mordaunt J, Walker P, Eadie N; BOTOX Glabellar Lines I Study Group. A multicenter, double-blind, randomized, placebo-controlled study of the efficacy and safety of botulinum toxin type A in the treatment of glabellar lines. J Am Acad Dermatol. 2002 Jun;46(6):840-9. doi: 10.1067/mjd.2002.121356.
• Carruthers J, Fagien S, Matarasso SL; Botox Consensus Group. Consensus recommendations on the use of botulinum toxin type a in facial aesthetics. Plast Reconstr Surg. 2004 Nov;114(6 Suppl):1S-22S. doi: 10.1097/01.PRS.0000144795.76040.D3.

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2021
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: October 6, 2021
• First Submitted That Met QC Criteria: October 6, 2021
• First Posted (Actual): October 19, 2021

Study Record Updates

• Last Update Posted (Actual): October 27, 2021
• Last Update Submitted That Met QC Criteria: October 20, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: wrinkles; onabotulinumtoxinA
• 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, Type A; abobotulinumtoxinA
• Other Study ID Numbers: CTBH-005

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
• product manufactured in and exported from the U.S.: No