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

NCT02677298 | Completed Phase 3 Results

• 2 other identifiers: CPH-301-2010302015-002164-16
• Study Type: interventional
• Target: 784
• Locations: 3 countries
• Sites: 18

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.

Conditions

Glabellar Frown Lines

Outcome Measures

Primary Outcomes (1)

• Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at Week 4 Visit Relative to Baseline, Based on Both the Investigators´ and the Subjects´ In-clinic Assessments.

  The primary endpoint is the percentage of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 4 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. Thus, the primary endpoint is a composite endpoint comprising investigator and subject assessments of treatment effectiveness. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles.

  Week 4

Secondary Outcomes (24)

• Percentage of Responders at Maximum Frown at Week 12

  Week 12

• Percentage of Responders at Week 16

  Week 16

• The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest at Week 4 Based Separately on the Investigators´ and the Subjects´ In-clinic Assessments

  Week 4

• Percentage of Responders at Week 20 or Later (After the First Treatment).

  Week 20, 24, 28, 32 of Treatment Cycle 1

• Extent of Change in Psychological Impact

  Week 4

Study Arms (3)

Botulinum toxin A

EXPERIMENTAL

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.

Drug: Botulinum Toxin A

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Botulinum toxin A Open Label Extension Arm

EXPERIMENTAL

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.

Drug: Botulinum Toxin A

Interventions

Botulinum Toxin A DRUG

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

Also known as: BoNT/A-DP

Botulinum toxin A

Placebo DRUG

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

Also known as: sodium chloride 0.9%

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Croma-Pharma GmbH: lead

Study Sites (18)

Total Skin And Beauty Dermatology Center, Pc

Birmingham, Alabama, 35205, United States

Location

Clinical Testing of Beverly Hills

Encino, California, 91436, United States

Location

Maas Clinic

San Francisco, California, 94115, United States

Location

About Skin

Greenwood Village, Colorado, 80111, United States

Location

DeNova Research

Chicago, Illinois, 60611, United States

Location

Skin Specialists

Omaha, Nebraska, 68144, United States

Location

Aesthetic Solutions

Chapel Hill, North Carolina, 27517, United States

Location

Society Hill Dermatology

Philadelphia, Pennsylvania, 19104, United States

Location

Tennessee Clinical Research Center

Nashville, Tennessee, 37215, United States

Location

Praxisklinik Fur Dermatologie, Hautzentrum am Starnberger See

Starnberg, Bavaria, 82319, Germany

Location

Rosenpark Research

Darmstadt, Hesse, 64283, Germany

Location

RZANY & HUND, Privatpraxis

Berlin, 10707, Germany

Location

S-thetic Clinic Hamburg

Hamburg, Germany

Location

Praxis Klinik Dr. Med. Anita Ruetter

Münster, Germany

Location

Carpe Diem, Centre for Aesthetic Medicine

Warsaw, Poland

Location

Clinical Research Group Sp. z o.o.

Warsaw, Poland

Location

Estederm Dr Marcin Ambroziak

Warsaw, Poland

Location

High-Med. Przychodnia Specjalistyczna

Warsaw, Poland

Location

Related Publications (1)

• 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.

  PMID: 38470985 DERIVED

MeSH Terms

Interventions

Botulinum Toxins, Type A; Sodium Chloride

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Clinical Development - Head of Clinical Operations
• Organization: Croma Pharma

clinical.studies@croma.at

+432262684680

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2015
• First Posted: February 9, 2016
• Study Start: March 2, 2016
• Primary Completion: November 23, 2016
• Study Completion: November 16, 2017
• Last Updated: March 19, 2025
• Results First Posted: March 19, 2025

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (9); PL (4); DE (5)