Clinical trial NCT02677805: Botulinum Toxin Treatment of Glabellar Lines: Efficacy and Safety Study II
Official title: Randomized Double Blind Phase 3 Study to Assess the Efficacy and Safety of BoNT/A-DP in the Treatment of Glabellar Lines in Comparison With Placebo Followed by an Open Label Extension Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glabellar Frown Lines
Lead sponsor: Croma-Pharma GmbH
Sponsor class: INDUSTRY
First posted: 2016-02-09
Enrollment: 251
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Aged ≥ 18 years or older at time of screening 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 effective birth control during the course of the study.
* 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 the Social Functioning subscale 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:

* At time of re-treatment subject does not have relevant changes to their health status from enrollment, which would have prevented subject's entry into the study according to the inclusion and exclusion criteria
* 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.

Primary outcomes:
measure: 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
timeFrame: Week 4
Secondary outcomes:
measure: Percentage of Responders at Maximum Frown at Week 12
timeFrame: Week 12
measure: Percentage of Responders at Maximum Frown at Week 16
timeFrame: Week 16
measure: 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
timeFrame: Week 4
measure: Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32
timeFrame: Week 20, Week 24, Week 28, Week 32
measure: Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines)
timeFrame: Week 4
measure: Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8
timeFrame: Week 1, Week 2, Week 8
measure: Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs
timeFrame: Week 2, Week 4, Week 12, Week 16, Week 20
measure: Time to Onset of Effect in the BoNT/A-DP and Placebo Groups in the First Treatment Cycle
timeFrame: From treatment at Day 0 to Week 4 in Treatment Cycle 1
measure: Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale
timeFrame: Week 4 of Treatment Cycles 1, 2, 3 and 4
measure: Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs
timeFrame: Week 2, Week 4, Week 12, Week 16, Week 20, Week 24, Week 28
measure: Percentage of Subjects With a Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at 4 Weeks After Re-treatment Relative to the Rating at the Preceding End-of-Cycle Visit
timeFrame: Week 4 of Treatment Cycles 2, 3 and 4
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs)
timeFrame: Through study completion (60 weeks)
measure: Number of Participants With Neutralizing Anti-Drug Antibodies
timeFrame: Through study completion (60 weeks)
measure: Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase
timeFrame: Week 4 of each treatment cycle
measure: Change From Baseline of Bilirubin, Creatinine
timeFrame: Week 4 of each treatment cycle
measure: Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen
timeFrame: Week 4 of each treatment cycle
measure: Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets
timeFrame: Week 4 of each treatment cycle
measure: Change From Baseline of Erythrocytes
timeFrame: Week 4 of each treatment cycle
measure: Change From Baseline of Erythrocyte MCHC, Hemoglobin
timeFrame: Week 4 of each treatment cycle
measure: Change From Baseline of of Erythrocyte MCV
timeFrame: Week 4 of each treatment cycle
measure: Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes
timeFrame: Week 4 of each treatment cycle
measure: Change From Baseline of Systolic and Diastolic Blood Pressure
timeFrame: Week 4 of Treatment Cycles 1, 2, 3 and 4
measure: Change From Baseline of Pulse Rate
timeFrame: Week 4 of Treatment Cycles 1, 2, 3 and 4
measure: Number of Participants With Normal and Abnormal Electrocardiogram
timeFrame: Last visit of Treatment Cycle 1 (End of Cycle procedures) conducted upon confirmation of eligibility for retreatment, which was assessed starting 12 weeks post-treatment with 4-weekly evaluations up to a maximum of 48 weeks post treatment.
Other outcomes:
Locations:
city: Encinitas
country: United States
facility: California Dermatology & Clinical Research Institute
state: California
city: Aventura
country: United States
facility: Center for Clinical and Cosmetic Research
state: Florida
city: Sarasota
country: United States
facility: Holcomb Kreithen Plastic Surgery
state: Florida
city: Hillsborough
country: United States
facility: Skin Laser And Surgery Specialists Of New York & New Jersey
state: New Jersey
city: Mount Kisco
country: United States
facility: The Center for Dermatology, Cosmetic & Laser Surger
state: New York
city: New York
country: United States
facility: Lorenc Aesthetic Plastic Surgery Center
state: New York
city: Plano
country: United States
facility: Skintastic Medical
state: Texas
Study officials:
References: