Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study I

NCT ID: NCT02677298

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 784 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-02
• Study Completion Date: 2017-11-16

Brief Summary

The aim of this study is to assess the efficacy and safety of BoNT/A-DP in the treatment of glabellar lines in comparison with placebo, including efficacy after repeat treatments and long term safety.

Detailed Description

This multicenter Phase 3 study is comprised of two parts. The first part of the study is a randomized, double blind, placebo-controlled, phase which aims to demonstrate efficacy and safety of BoNT/A-DP compared with placebo. The second part is an open label extension phase to evaluate efficacy after repeat treatments and long term safety. Subjects can receive a maximum of four treatment cycles over the duration of the study, a single treatment in the first cycle compared with placebo, and up to three subsequent treatments in the open label extension study.

Conditions

Glabellar Frown Lines

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Botulinum toxin A

Botulinum Toxin A (Clostridium botulinum toxin type A) will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area.

Group Type: EXPERIMENTAL

Botulinum Toxin A

Intervention Type: DRUG

Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.

Placebo

Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Injection, 0.9% sodium chloride divided in five 0.1 mL i.m. injections into glabellar area

Botulinum toxin A Open Label Extension Arm

Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles.

20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area.

Group Type: EXPERIMENTAL

Botulinum Toxin A

Intervention Type: DRUG

Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area in up to 3 treatment cycles

Interventions

Botulinum Toxin A

Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area.

Intervention Type: DRUG

Placebo

Injection, 0.9% sodium chloride divided in five 0.1 mL i.m. injections into glabellar area

Intervention Type: DRUG

Botulinum Toxin A

Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area in up to 3 treatment cycles

Intervention Type: DRUG

Other Intervention Names

BoNT/A-DP; sodium chloride 0.9%; BoNT/A-DP

Eligibility Criteria

Inclusion Criteria

• Aged ≥ 18 years or older at the time of screening (upper limit 75 years, inclusive).
• Has moderate to severe glabellar frown lines at maximum frown (severity score of 2 or 3 on FWS) as determined by in-clinic assessments by both the investigator and the subject (where: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe').
• Subject has a stable medical condition with no uncontrolled systemic disease.
• Female subjects of childbearing potential must test negative for pregnancy and agree to use highly effective birth control during the course of the study. Such methods include for example: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion or vasectomized partner.
• Subjects who wear glasses must be able to adequately self-assess the severity of their glabellar lines (according to the FWS), without glasses obstructing the forehead area.
• The moderate to severe glabellar lines have an important psychological impact on the subject, as indicated by scores >0 on either the Emotional or Functioning subscales of the modified Skindex-16 (GL-QoL).

Exclusion Criteria

• Previous treatment with any serotype of botulinum toxin for any indication within the 12 months prior to screening, or any planned treatment with botulinum toxin of any serotype for any reason during the trial (other than the investigational treatment).
• Known hypersensitivity to the study medication or its excipients.
• Any medical condition that may place the subject at increased risk due to exposure to botulinum toxin, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, profound atrophy or weakness in the target muscles, or any other condition (at the investigator's discretion) that might interfere with neuromuscular function or contraindicate botulinum toxin therapy.
• Facial laser or light treatment, microdermabrasion, superficial peels or retinoid therapy within the 3 months prior to screening or planned during the study.
• Apart from the procedures specified above, previous treatment with any facial aesthetic procedure in the glabellar area (including chemical peeling, injection with biodegradable fillers,) within 12 months prior to screening or planned during the study.
• Previous insertion of permanent material in the glabellar area or planned during the study.
• Any surgery, or history of surgery, in the glabellar area including surgical removal of the corrugator, procerus or depressor supercili muscles or a combination of these, or scars in the glabellar area, or such surgery planned during the study.
• Active skin disease/infection or irritation at the treatment area.
• Inability to substantially lessen glabellar frown lines even by physically spreading them apart.
• Use of a muscle relaxant within 2 weeks prior to screening or planned during the study.
• Marked facial asymmetry or ptosis of eyelid and/or eyebrow, or current facial palsy or neuromuscular junction disorders as judged by the investigator.
• Pregnant, breastfeeding or planning to become pregnant during the trial.
• Use of prohibited medication including anticholinergic drugs, or drugs which could interfere with neuromuscular function, including aminoglycoside antibiotics and curare-like compounds within 2 weeks prior to screening or planned during the study.
• Planned surgery with general anaesthetic (use of local anaesthetic outside the glabellar area is permitted).
• Participation in another clinical study within one month of screening and throughout the trial.
• Previous participation in another botulinum toxin aesthetic study which involved the treatment of glabellar lines in combination with canthal lines and/or forehead lines in the previous 18 months.
• Chronic drug or alcohol abuse (as per investigator discretion).

Eligibility Criteria for re-treatment: The following criteria MUST be met for re-treatment:

• The subject must have been randomized to receive treatment and must have received at least one treatment (BoNT/A-DP or placebo).
• A minimum of 12 weeks must have elapsed since the previous study treatment.
• The subject's glabellar lines at maximum frown must have relapsed to a FWS score of 2 or 3 as determined by the investigator and the subject.
• No relevant infection or inflammation in the planned injection area.
• Negative urine pregnancy test, in women of child-bearing potential.
• The subject must have received fewer than four study treatments.
• The subject must agree and consent to re-treatment.
• Re-treatment will be performed at the latest by week 48.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Croma-Pharma GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Total Skin And Beauty Dermatology Center, Pc

Birmingham, Alabama, United States

Clinical Testing of Beverly Hills

Encino, California, United States

Maas Clinic

San Francisco, California, United States

About Skin

Greenwood Village, Colorado, United States

DeNova Research

Chicago, Illinois, United States

Skin Specialists

Omaha, Nebraska, United States

Aesthetic Solutions

Chapel Hill, North Carolina, United States

Society Hill Dermatology

Philadelphia, Pennsylvania, United States

Tennessee Clinical Research Center

Nashville, Tennessee, United States

Praxisklinik Fur Dermatologie, Hautzentrum am Starnberger See

Starnberg, Bavaria, Germany

Rosenpark Research

Darmstadt, Hesse, Germany

RZANY & HUND, Privatpraxis

Berlin, , Germany

S-thetic Clinic Hamburg

Hamburg, , Germany

Praxis Klinik Dr. Med. Anita Ruetter

Münster, , Germany

Carpe Diem, Centre for Aesthetic Medicine

Warsaw, , Poland

Clinical Research Group Sp. z o.o.

Warsaw, , Poland

Estederm Dr Marcin Ambroziak

Warsaw, , Poland

High-Med. Przychodnia Specjalistyczna

Warsaw, , Poland

Countries

United States; Germany; Poland

References

Cox SE, Kaufman-Janette J, Cohen JL, Gold M, Joseph J, Nestor MS, Rzany B, Taylor S, Zhou J, Cecerle M, Pueraro E, Irvine R, Dayan S. LetibotulinumtoxinA Attenuates the Psychological Burden of Glabellar Lines and Is Associated With High Subject Satisfaction in Phase 3 Clinical Trials. Dermatol Surg. 2024 Jun 1;50(6):535-541. doi: 10.1097/DSS.0000000000004152. Epub 2024 Mar 12.

Reference Type: DERIVED

PMID: 38470985 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-002164-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CPH-301-201030

Identifier Type: -

Identifier Source: org_study_id