Glabellar Frown Lines
Conditions
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
The study is a parallel-group, randomized, double blind, placebo-controlled study followed by an open label extension. An interim Analysis will be performed when all subjects finalized the re-evaluation for retreatment visit at week 16 of the first treatment cycle or completed the double blind phase (whichever occurs earlier). The first treatment cycle of the study will comprise two treatment groups as follows: * Group A (active): BoNT/A-DP (20 units, 0.5 mL) * Group B (placebo control): sterile, 0.9% sodium chloride, (0.5 mL). Eligible subjects will be randomized at baseline (day 0) to Group A or B to receive the first treatment in a 3:1 randomization scheme, respectively. Investigators and subjects will be blinded to the treatment administered and will evaluate the severity of glabellar lines independently. The subject should perform their assessment independently and ideally before the investigator, to ensure they are not biased by the investigator. The same investigator should assess the subject at baseline and at the visits at weeks 1, 2 and 4 in the first treatment cycle. After a screening period of up to14 calendar days, subjects will receive the first treatment (BoNT/A-DP or placebo) and attend for visits at 1, 2 and 4 weeks after treatment and at 4 weekly intervals thereafter for evaluation of efficacy and safety (primary and key secondary efficacy endpoints are evaluated in the first treatment cycle in comparison with placebo). The first treatment cycle will last at least 12 weeks and will end when the subjects qualify for re-treatment (in accordance with the eligibility for re-treatment criteria). After the first treatment cycle is completed, all subjects may enter the open label extension phase and will be dosed with BoNT/A-DP (20 U) for subsequent re-treatments. Evaluation for re-treatment takes place at the earliest at 12 weeks after the first/previous treatment. Subjects who do not qualify for re-treatment at week 12 will have the option (pending eligibility) of re-treatment at a later visit (at 4 weekly intervals thereafter) until they are eligible for re-treatment or until a total of 48 weeks has elapsed since study start. Subjects will attend for visits at 1 and 4 weeks after any re-treatment and at 4 weekly intervals thereafter. At week 2 and week 8 of each open label cycle a telephone call visit will take place. According to the study schedule (Section 2.1 and Section 2.2), a maximum of 4 treatments per subject (4 treatment cycles) is permitted during the study time frame, with treatments separated by a minimum of 12 weeks. The number of treatments administered per subject will depend on the subject's qualification for re-treatment; however, the last opportunity for re-treatment is at week 48.
Interventions
DRUGBotulinum Toxin A
Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area
DRUGPlacebo
injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area
Sponsors
Croma-Pharma GmbH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Ages ≥ 18 years or older at 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 had a stable medical condition with no uncontrolled systemic disease. * Female subjects of childbearing potential had to test negative for pregnancy and agree to use effective birth control during the course of the study. * Subjects who wear glasses had to be able to adequately self-assess the severity of their glabellar lines (according to the FWS), without glasses obstructing the forehead area. * Moderate to severe glabellar lines indicating 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 scale.
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 study (other than the investigational treatment). * Known hypersensitivity to the study drug 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 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 trail (other than the investigational treatment). * 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 supercilii 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.2 * 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 study. * Use of prohibited medication including anticholinergic drugs, or drugs that could interfere with neuromuscular function, including aminoglycoside antibiotics and curare-like compounds within 2 weeks prior to screening or planned during the study.2 * Planned surgery with general anesthetic (use of local anesthetic outside the glabellar area was permitted). * Participation in another clinical study within 1 month of screening and throughout the study. * Previous participation in another botulinum toxin aesthetic study which involved the treatment of glabellar lines in combination with canthal lines and/or forehead lines, within the previous 18 months. * Chronic drug or alcohol abuse (as per investigator discretion). Eligibility Criteria for Retreatment The following criteria had to be met for retreatment: * At time of retreatment, the subject did not have relevant changes to their health status from enrolment, which could have prevented the subject's entry into the study according to the inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Week 4 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | Week 4 | Extent of change in psychological impact at week 4 after first treatment, relative to baseline, assessed by * modified Skindex-16 (Glabellar Line Quality of Life Scale, \[GL-QoL\]): Each of 7 items rated on 5-point scale: 0/Never, 1/Rarely, 2/Sometimes, 3/Often, 4/Always bothered, than rescaled to a 0 to 100 standardized score; Emotional Domain is the mean of 4 of the items; Social Functioning Domain is the mean of 3 of the items; Overall score is the mean of all 7 items. All reported scores ranging from 0 (best outcome) to 100 (worst outcome). * validated FACE-Q Appraisal of Lines Between Eyebrows scale: Each of 7 items rated on 4-point scale: 1/Not at all, 2/a little, 3/moderately, 4/extremely. Reported score is the sum of the 7 items, standardized on a scale from 0 (worst outcome) to 100 (best outcome). * Age Appraisal visual analog scale \[VAS\]: Perception of Age compared to actual age, in years ranging from -15 years (best outcome) to +15 years (worst outcome). |
| Percentage of Responders at Maximum Frown at Week 12 | Week 12 | 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 12 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. 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. |
| Percentage of Responders at Week 16 | Week 16 | 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 16 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. 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. |
| Percentage of Responders at Week 20 | Week 20 | 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 20 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. 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. |
| 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 | The Percentage of subjects with a ≥ 1 point reduction in Facial Wrinkle Scale (FWS) score at rest at week 4 in the first treatment cycle, based separately on the investigators' and the subjects' in-clinic assessments (applicable only for subjects who have a FWS score at rest ≥ 1 at baseline). 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. |
| Responder Rate at Weeks 1, 2 and 8 | Week 1, Week 2 and Week 8 | The Percentage of responders among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score at maximum frown of 0 or 1 and an improvement ≥ 2 points in FWS score (at maximum frown) during the first treatment cycle visit relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint, at weeks 1, 2 and 8). 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. |
| The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | Week 2, 4, 12, 16 and 20 | The percentage of subjects with ≥ 2-point and ≥ 1 reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle visit relative to baseline, based on the independent rater's assessment of photographs (at baseline and visits 2, 4, 12, 16 and 20 weeks after treatment, within the first treatment cycle). The median value of all assessments of the same photography was considered for analysis. 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. |
| Time to Onset of Effect in the BoNT/A-DP and Placebo Groups in the First Treatment Cycle | From treatment at Day 0 to Week 4 in Treatment Cycle 1 | Time to onset of effect in the BoNT/A-DP and placebo groups in the first treatment cycle, as measured at weeks 1, 2 and 4 based separately on subject and investigator assessment. Onset of effect defined as at least a 1 point improvement in Facial Wrinkle Scale (FWS) score from baseline (at maximum frown). 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. |
| Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | The extent of subject perceptions of effect of, and satisfaction with, treatment in the BoNT/A-DP and placebo groups, during each treatment cycle, as assessed by the validated FACE-Q Satisfaction with Outcome Scale. The FACE-Q Satisfaction with Outcome scale is a patient-reported outcome measure designed to assess a patient's satisfaction with the results of a facial aesthetic procedure. This scale comprises six items, each with four response options: definitely agree, somewhat agree, somewhat disagree, and definitely disagree. |
| The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 2, Week 4, Week 12, Week 16, Week 20 of Treatment Cycle 1 | The percentage of subjects with a ≥ 1 point reduction in Facial Wrinkle Scale (FWS) score at rest in the BoNT/A-DP and placebo groups, relative to baseline, during the first treatment cycle, based on the independent rater's assessment of photos. The median value of all assessments of the same photography was considered for analysis. 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. |
| 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. | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | The 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, based on both the investigator's and the subject's in-clinic assessments (composite endpoint). 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. |
| The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 of Treatment Cycle 1 | The percentage of subjects with ≥ 1-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle at week 1, 2, 4, 8, 12, 16 and 20 relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). For week 16 and 20 subjects who were re-treated before the respective visits were counted as non-responders. 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Through study completion (60 weeks) | Number of Participants with treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest (AESIs) |
| Number of Participants With Neutralizing Anti-Drug Antibodies | Through study completion (60 weeks) | Number of Participants with Neutralizing Anti-Drug Antibodies Antibody formation, evaluation pre-dose before each treatment, at 4 weeks after each treatment and at the final study visit. |
| Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | Safety assessments by evaluating change from baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets as per the study schedule |
| Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | Safety assessments by evaluating change from baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase as per the study schedule |
| Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | Safety assessments by evaluating change from baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen as per the study schedule |
| Change From to Baseline of Bilirubin, Creatinin | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | Safety assessments by evaluating change from baseline of Bilirubin, Creatinin as per the study schedule |
| Change From Baseline of Erythrocytes | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | Safety assessments by evaluating change from baseline of Erythrocytes as per the study schedule |
| Change From Baseline of Erythrocytes MCV | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | Safety assessments by evaluating change from baseline of Erythrocytes MCV as per the study schedule |
| Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | Safety assessments by evaluating change from baseline of Erythrocyte MCHC, Hemoglobin as per the study schedule |
| Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | Safety assessments by evaluating change from baseline of Lymphocytes/leukocytes, Monocytes/leukocytes, Neutrophils/leukocytes, Basophiles/leukocytes, Eosinophils/leukocytes as per the study schedule |
| Change From Baseline of Systolic and Diastolic Blood Pressure | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | Safety assessments by evaluating change from baseline of Systolic and Diastolic Blood Pressure as per the study schedule |
| Change From Baseline of Pulse Rate | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | Safety assessments by evaluating change from baseline of Pulse rate as per the study schedule |
| Number of Participants With Normal and Abnormal Electrocardiogram | Week 4 and last visit of Treatment Cycle 1 (End of Cycle procedures), conducted upon confirmation of eligibility for retreatment, assessed starting 12 weeks post-treatment with 4-weekly evaluations up to a max. of 48 weeks post treatment. | Safety assessments by evaluating Electrocardiogram as per the study schedule |
| The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During Each Re-treatment Cycle at Week 4 Relative to Re-treatment-baseline. | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) | The percentage of subjects with ≥ 1-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP during each re-treatment cycle at week 4 relative to re-treatment baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). 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. |
Countries
United States
Participant flow
Pre-assignment details
Of 410 enrolled participants, 355 met inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin A Botulinum Toxin 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 glabellar area.
Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area | 266 |
| Placebo Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area.
Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area | 89 |
| Total | 355 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Phase | COVID-19 | 1 | 0 | 0 |
| Double-Blind Phase | Early Termination due to Botox Injection while Participating in the Study | 1 | 0 | 0 |
| Double-Blind Phase | Lost to Follow-up | 4 | 3 | 0 |
| Double-Blind Phase | Physician Decision | 1 | 0 | 0 |
| Double-Blind Phase | Withdrawal by Subject | 9 | 2 | 0 |
| Open-Label Phase | Lost to Follow-up | 0 | 0 | 13 |
| Open-Label Phase | Physician Decision | 0 | 0 | 2 |
| Open-Label Phase | Withdrawal by Subject | 0 | 0 | 11 |
Baseline characteristics
| Characteristic | Botulinum Toxin A | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 33 Participants | 8 Participants | 41 Participants |
| Age, Categorical Between 18 and 65 years | 233 Participants | 81 Participants | 314 Participants |
| Age, Continuous | 52.2 years STANDARD_DEVIATION 11.24 | 49.4 years STANDARD_DEVIATION 12.36 | 51.5 years STANDARD_DEVIATION 11.58 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 66 Participants | 22 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 200 Participants | 67 Participants | 267 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Investigator's In-clinic Assessment Mild facial wrinkles | 0 Participants | 0 Participants | 0 Participants |
| Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Investigator's In-clinic Assessment Moderate facial wrinkles | 64 Participants | 22 Participants | 86 Participants |
| Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Investigator's In-clinic Assessment No facial wrinkles | 0 Participants | 0 Participants | 0 Participants |
| Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Investigator's In-clinic Assessment Severe facial wrinkles | 202 Participants | 67 Participants | 269 Participants |
| Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Subject's In-clinic Assessment Mild facial wrinkles | 0 Participants | 0 Participants | 0 Participants |
| Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Subject's In-clinic Assessment Moderate facial wrinkles | 70 Participants | 25 Participants | 95 Participants |
| Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Subject's In-clinic Assessment No facial wrinkles | 0 Participants | 0 Participants | 0 Participants |
| Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment Subject's In-clinic Assessment Severe facial wrinkles | 196 Participants | 64 Participants | 260 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 7 Participants | 32 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 236 Participants | 79 Participants | 315 Participants |
| Region of Enrollment Austria | 41 Participants | 10 Participants | 51 Participants |
| Region of Enrollment United States | 225 Participants | 79 Participants | 304 Participants |
| Sex: Female, Male Female | 248 Participants | 80 Participants | 328 Participants |
| Sex: Female, Male Male | 18 Participants | 9 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 266 | 0 / 89 | 0 / 323 |
| other Total, other adverse events | 12 / 266 | 6 / 89 | 14 / 323 |
| serious Total, serious adverse events | 1 / 266 | 1 / 89 | 4 / 323 |
Outcome results
Primary
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.
Time frame: Week 4
Population: The population used consists of all randomized subjects, regardless of whether they received study medication. Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale (FWS) at baseline or week 4 were assigned as being non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Botulinum Toxin 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 Relative to Baseline, Based on Both the Investigators´ and the Subjects´ In-clinic Assessments. | 172 Participants |
| Placebo | 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. | 0 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase
Safety assessments by evaluating change from baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase as per the study schedule
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 1 - Alanine Aminotransferase (U/L) | -0.1 U/L | Standard Deviation 9.32 |
| Botulinum Toxin A | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 1 - Gamma Glutamyl Transpeptidase (U/L) | 0.8 U/L | Standard Deviation 50.89 |
| Botulinum Toxin A | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 1 - Alkaline phosphatase (U/L) | -0.8 U/L | Standard Deviation 10.99 |
| Botulinum Toxin A | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 1 - Aspartate Aminotransferase (U/L) | 0.2 U/L | Standard Deviation 11.28 |
| Placebo | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 1 - Aspartate Aminotransferase (U/L) | 0.1 U/L | Standard Deviation 8.63 |
| Placebo | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 1 - Alkaline phosphatase (U/L) | -0.5 U/L | Standard Deviation 12.3 |
| Placebo | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 1 - Gamma Glutamyl Transpeptidase (U/L) | 0.8 U/L | Standard Deviation 12.41 |
| Placebo | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 1 - Alanine Aminotransferase (U/L) | 1.9 U/L | Standard Deviation 19.35 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 3 - Gamma Glutamyl Transpeptidase (U/L) | 0.0 U/L | Standard Deviation 9.64 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 4 - Alanine Aminotransferase (U/L) | -0.2 U/L | Standard Deviation 10.82 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 4 - Alkaline phosphatase (U/L) | 0.9 U/L | Standard Deviation 10.75 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 4 - Aspartate Aminotransferase (U/L) | -1.6 U/L | Standard Deviation 14.54 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 4 - Gamma Glutamyl Transpeptidase (U/L) | 1.0 U/L | Standard Deviation 9.59 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 2 - Alanine Aminotransferase (U/L) | 1.1 U/L | Standard Deviation 10.68 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 2 - Alkaline phosphatase (U/L) | 0.9 U/L | Standard Deviation 9.42 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 2 - Aspartate Aminotransferase (U/L) | -0.2 U/L | Standard Deviation 12.76 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 2 - Gamma Glutamyl Transpeptidase (U/L) | 1.3 U/L | Standard Deviation 11.09 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 3 - Alanine Aminotransferase (U/L) | -0.4 U/L | Standard Deviation 13.43 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 3 - Alkaline phosphatase (U/L) | 0.6 U/L | Standard Deviation 10.89 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Week 4 of cycle 3 - Aspartate Aminotransferase (U/L) | -1.0 U/L | Standard Deviation 14.73 |
Secondary
Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets
Safety assessments by evaluating change from baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets as per the study schedule
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Basophils (x10^9 cells/L) | 0.004 x10^9 cells/L | Standard Deviation 0.0413 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Neutrophils (x10^9 cells/L) | 0.027 x10^9 cells/L | Standard Deviation 1.3211 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Platelets (x10^9 cells/L) | 0.3 x10^9 cells/L | Standard Deviation 37.31 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Eosinophils (x10^9 cells/L) | 0.006 x10^9 cells/L | Standard Deviation 0.0726 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Leukocytes (x10^9 cells/L) | -0.029 x10^9 cells/L | Standard Deviation 1.4925 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Lymphocytes (x10^9 cells/L) | -0.038 x10^9 cells/L | Standard Deviation 0.4554 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Monocytes (x10^9 cells/L) | -0.027 x10^9 cells/L | Standard Deviation 0.1607 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Leukocytes (x10^9 cells/L) | 0.227 x10^9 cells/L | Standard Deviation 1.4308 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Monocytes (x10^9 cells/L) | -0.019 x10^9 cells/L | Standard Deviation 0.2154 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Eosinophils (x10^9 cells/L) | 0.007 x10^9 cells/L | Standard Deviation 0.0767 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Neutrophils (x10^9 cells/L) | 0.252 x10^9 cells/L | Standard Deviation 1.1477 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Lymphocytes (x10^9 cells/L) | -0.027 x10^9 cells/L | Standard Deviation 0.4222 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Platelets (x10^9 cells/L) | -0.8 x10^9 cells/L | Standard Deviation 38.87 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 1 - Basophils (x10^9 cells/L) | 0.012 x10^9 cells/L | Standard Deviation 0.0556 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 3 - Platelets (x10^9 cells/L) | 6.1 x10^9 cells/L | Standard Deviation 39.16 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 4 - Basophils (x10^9 cells/L) | -0.019 x10^9 cells/L | Standard Deviation 0.0475 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 4 - Leukocytes (x10^9 cells/L) | -0.404 x10^9 cells/L | Standard Deviation 1.58 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 4 - Lymphocytes (x10^9 cells/L) | 0.003 x10^9 cells/L | Standard Deviation 0.4665 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 4 - Monocytes (x10^9 cells/L) | -0.025 x10^9 cells/L | Standard Deviation 0.1698 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 4 - Neutrophils (x10^9 cells/L) | -0.344 x10^9 cells/L | Standard Deviation 1.3644 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 4 - Platelets (x10^9 cells/L) | 0.4 x10^9 cells/L | Standard Deviation 41.64 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 4 - Eosinophils (x10^9 cells/L) | -0.026 x10^9 cells/L | Standard Deviation 0.0859 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 2 - Basophils (x10^9 cells/L) | -0.002 x10^9 cells/L | Standard Deviation 0.0565 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 2 - Eosinophils (x10^9 cells/L) | 0.009 x10^9 cells/L | Standard Deviation 0.0998 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 2 - Leukocytes (x10^9 cells/L) | 0.000 x10^9 cells/L | Standard Deviation 1.5182 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 2 - Lymphocytes (x10^9 cells/L) | 0.043 x10^9 cells/L | Standard Deviation 0.4282 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 2 - Monocytes (x10^9 cells/L) | -0.002 x10^9 cells/L | Standard Deviation 0.1123 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 2 - Neutrophils (x10^9 cells/L) | -0.048 x10^9 cells/L | Standard Deviation 1.347 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 2 - Platelets (x10^9 cells/L) | 6.1 x10^9 cells/L | Standard Deviation 37.89 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 3 - Basophils (x10^9 cells/L) | -0.018 x10^9 cells/L | Standard Deviation 0.0496 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 3 - Eosinophils (x10^9 cells/L) | -0.002 x10^9 cells/L | Standard Deviation 0.1059 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 3 - Leukocytes (x10^9 cells/L) | -0.050 x10^9 cells/L | Standard Deviation 2.0753 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 3 - Lymphocytes (x10^9 cells/L) | 0.021 x10^9 cells/L | Standard Deviation 0.4473 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 3 - Monocytes (x10^9 cells/L) | -0.018 x10^9 cells/L | Standard Deviation 0.1246 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of cycle 3 - Neutrophils (x10^9 cells/L) | -0.034 x10^9 cells/L | Standard Deviation 1.9383 |
Secondary
Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen
Safety assessments by evaluating change from baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen as per the study schedule
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of cycle 1 - Cholesterol (mmol/L) | -0.119 mmol/L | Standard Deviation 0.6477 |
| Botulinum Toxin A | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 1 - Urea nitrogen (mmol/L) | 0.01 mmol/L | Standard Deviation 1.356 |
| Botulinum Toxin A | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 1 - Glucose (mmol/L) | 0.317 mmol/L | Standard Deviation 1.1751 |
| Botulinum Toxin A | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 1 - Potassium (mmol/L) | -0.06 mmol/L | Standard Deviation 0.405 |
| Botulinum Toxin A | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 1 - Sodium (mmol/L) | -0.1 mmol/L | Standard Deviation 2.39 |
| Placebo | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 1 - Potassium (mmol/L) | -0.09 mmol/L | Standard Deviation 0.431 |
| Placebo | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 1 - Sodium (mmol/L) | -0.3 mmol/L | Standard Deviation 2.35 |
| Placebo | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 1 - Glucose (mmol/L) | 0.290 mmol/L | Standard Deviation 0.9429 |
| Placebo | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 1 - Urea nitrogen (mmol/L) | 0.00 mmol/L | Standard Deviation 1.123 |
| Placebo | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of cycle 1 - Cholesterol (mmol/L) | -0.049 mmol/L | Standard Deviation 0.54 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 3 - Urea nitrogen (mmol/L) | 0.01 mmol/L | Standard Deviation 1.272 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 4 - Cholesterol (mmol/L) | 0.040 mmol/L | Standard Deviation 0.6614 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 4 - Glucose (mmol/L) | -0.098 mmol/L | Standard Deviation 1.9131 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 4 - Potassium (mmol/L) | 0.08 mmol/L | Standard Deviation 0.039 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 4 - Sodium (mmol/L) | 0.2 mmol/L | Standard Deviation 1.87 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 4 - Urea nitrogen (mmol/L) | 0.06 mmol/L | Standard Deviation 1.398 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of cycle 2 - Cholesterol (mmol/L) | 0.07 mmol/L | Standard Deviation 0.591 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 2 - Glucose (mmol/L) | 0.086 mmol/L | Standard Deviation 1.2927 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 2 - Potassium (mmol/L) | 0.03 mmol/L | Standard Deviation 0.391 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 2 - Sodium (mmol/L) | -0.1 mmol/L | Standard Deviation 2.28 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 2 - Urea nitrogen (mmol/L) | -0.05 mmol/L | Standard Deviation 1.277 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of cycle 3 - Cholesterol (mmol/L) | 0.021 mmol/L | Standard Deviation 0.7421 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 3 - Glucose (mmol/L) | 0.185 mmol/L | Standard Deviation 1.5644 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 3 - Potassium (mmol/L) | 0.03 mmol/L | Standard Deviation 0.415 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of of cycle 3 - Sodium (mmol/L) | 0.1 mmol/L | Standard Deviation 2.44 |
Secondary
Change From Baseline of Erythrocyte MCHC, Hemoglobin
Safety assessments by evaluating change from baseline of Erythrocyte MCHC, Hemoglobin as per the study schedule
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of cycle 1 - Hemoglobin (g/dL) | 0.02 g/dL | Standard Deviation 0.732 |
| Botulinum Toxin A | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of cycle 1 - Erythrocyte MCHC (g/dL) | 0.32 g/dL | Standard Deviation 0.954 |
| Placebo | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of cycle 1 - Hemoglobin (g/dL) | -0.09 g/dL | Standard Deviation 0.74 |
| Placebo | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of cycle 1 - Erythrocyte MCHC (g/dL) | 0.33 g/dL | Standard Deviation 1.041 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of cycle 3 - Hemoglobin (g/dL) | -0.21 g/dL | Standard Deviation 0.821 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of cycle 4 - Erythrocyte MCHC (g/dL) | -0.65 g/dL | Standard Deviation 1.306 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of cycle 4 - Hemoglobin (g/dL) | -0.15 g/dL | Standard Deviation 0.921 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of cycle 2 - Erythrocyte MCHC (g/dL) | 0.16 g/dL | Standard Deviation 1.07 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of cycle 2 - Hemoglobin (g/dL) | 0.12 g/dL | Standard Deviation 0.638 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of cycle 3 - Erythrocyte MCHC (g/dL) | -0.12 g/dL | Standard Deviation 1.366 |
Secondary
Change From Baseline of Erythrocytes
Safety assessments by evaluating change from baseline of Erythrocytes as per the study schedule
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Erythrocytes | Cycle 1 | -0.002 x10^12 cells/L | Standard Deviation 0.2425 |
| Placebo | Change From Baseline of Erythrocytes | Cycle 1 | -0.038 x10^12 cells/L | Standard Deviation 0.2194 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocytes | Cycle 2 | 0.032 x10^12 cells/L | Standard Deviation 0.2091 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocytes | Cycle 3 | 0.063 x10^12 cells/L | Standard Deviation 0.2619 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocytes | Cycle 4 | 0.041 x10^12 cells/L | Standard Deviation 0.2716 |
Secondary
Change From Baseline of Erythrocytes MCV
Safety assessments by evaluating change from baseline of Erythrocytes MCV as per the study schedule
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Erythrocytes MCV | Cycle 1 | -0.78 fL | Standard Deviation 2.615 |
| Placebo | Change From Baseline of Erythrocytes MCV | Cycle 1 | -0.79 fL | Standard Deviation 2.86 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocytes MCV | Cycle 2 | -0.38 fL | Standard Deviation 3.07 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocytes MCV | Cycle 3 | 0.53 fL | Standard Deviation 4.209 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocytes MCV | Cycle 4 | 2.18 fL | Standard Deviation 3.875 |
Secondary
Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes
Safety assessments by evaluating change from baseline of Lymphocytes/leukocytes, Monocytes/leukocytes, Neutrophils/leukocytes, Basophiles/leukocytes, Eosinophils/leukocytes as per the study schedule
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 1 - Basophiles/leukocytes (%) | 0.05 % of leukocytes | Standard Deviation 0.669 |
| Botulinum Toxin A | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 1 - Neutrophils/leukocytes (%) | 0.47 % of leukocytes | Standard Deviation 7.61 |
| Botulinum Toxin A | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 1 - Eosinophils/leukocytes (%) | 0.14 % of leukocytes | Standard Deviation 1.09 |
| Botulinum Toxin A | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 1 - Lymphocytes/leukocytes (%) | -0.26 % of leukocytes | Standard Deviation 6.724 |
| Botulinum Toxin A | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 1 - Monocytes/leukocytes (%) | -0.40 % of leukocytes | Standard Deviation 2.337 |
| Placebo | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 1 - Lymphocytes/leukocytes (%) | -1.13 % of leukocytes | Standard Deviation 5.468 |
| Placebo | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 1 - Monocytes/leukocytes (%) | -0.48 % of leukocytes | Standard Deviation 2.35 |
| Placebo | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 1 - Eosinophils/leukocytes (%) | 0.05 % of leukocytes | Standard Deviation 1.292 |
| Placebo | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 1 - Neutrophils/leukocytes (%) | 1.41 % of leukocytes | Standard Deviation 6.219 |
| Placebo | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 1 - Basophiles/leukocytes (%) | 0.14 % of leukocytes | Standard Deviation 0.89 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 3 - Neutrophils/leukocytes (%) | -0.47 % of leukocytes | Standard Deviation 9.24 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 4 - Basophiles/leukocytes (%) | -0.23 % of leukocytes | Standard Deviation 0.663 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 4 - Eosinophils/leukocytes (%) | -0.26 % of leukocytes | Standard Deviation 1.191 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 4 - Lymphocytes/leukocytes (%) | 1.68 % of leukocytes | Standard Deviation 6.869 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 4 - Monocytes/leukocytes (%) | 0.06 % of leukocytes | Standard Deviation 2.434 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 4 - Neutrophils/leukocytes (%) | -1.34 % of leukocytes | Standard Deviation 7.46 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 2 - Basophiles/leukocytes (%) | -0.04 % of leukocytes | Standard Deviation 0.837 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 2 - Eosinophils/leukocytes (%) | 0.13 % of leukocytes | Standard Deviation 1.554 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 2 - Lymphocytes/leukocytes (%) | 0.80 % of leukocytes | Standard Deviation 6.802 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 2 - Monocytes/leukocytes (%) | -0.04 % of leukocytes | Standard Deviation 1.559 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 2 - Neutrophils/leukocytes (%) | -0.84 % of leukocytes | Standard Deviation 7.66 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 3 - Basophiles/leukocytes (%) | -0.25 % of leukocytes | Standard Deviation 0.764 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 3 - Eosinophils/leukocytes (%) | 0.06 % of leukocytes | Standard Deviation 1.788 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 3 - Lymphocytes/leukocytes (%) | 0.82 % of leukocytes | Standard Deviation 7.814 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Week 4 of cycle 3 - Monocytes/leukocytes (%) | -0.16 % of leukocytes | Standard Deviation 1.79 |
Secondary
Change From Baseline of Pulse Rate
Safety assessments by evaluating change from baseline of Pulse rate as per the study schedule
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Pulse Rate | Cycle 1 | -1.7 bpm | Standard Deviation 10.83 |
| Placebo | Change From Baseline of Pulse Rate | Cycle 1 | 0.1 bpm | Standard Deviation 10.24 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Pulse Rate | Cycle 2 | 1.2 bpm | Standard Deviation 9.11 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Pulse Rate | Cycle 3 | 2.2 bpm | Standard Deviation 10.73 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Pulse Rate | Cycle 4 | 0.7 bpm | Standard Deviation 10.73 |
Secondary
Change From Baseline of Systolic and Diastolic Blood Pressure
Safety assessments by evaluating change from baseline of Systolic and Diastolic Blood Pressure as per the study schedule
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of cycle 1 - Diastolic Blood Pressure (mmHg) | -1.0 mmHg | Standard Deviation 7.54 |
| Botulinum Toxin A | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of cycle 1 - Systolic Blood Pressure (mmHg) | -0.7 mmHg | Standard Deviation 11.13 |
| Placebo | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of cycle 1 - Diastolic Blood Pressure (mmHg) | 1.3 mmHg | Standard Deviation 8.16 |
| Placebo | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of cycle 1 - Systolic Blood Pressure (mmHg) | -0.2 mmHg | Standard Deviation 10.5 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of cycle 3 - Diastolic Blood Pressure (mmHg) | -0.4 mmHg | Standard Deviation 8.02 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of cycle 4 - Systolic Blood Pressure (mmHg) | -1.8 mmHg | Standard Deviation 13.4 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of cycle 4 - Diastolic Blood Pressure (mmHg) | -0.2 mmHg | Standard Deviation 7.38 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of cycle 2 - Systolic Blood Pressure (mmHg) | -0.9 mmHg | Standard Deviation 11.66 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of cycle 2 - Diastolic Blood Pressure (mmHg) | 0.0 mmHg | Standard Deviation 7.79 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of cycle 3 - Systolic Blood Pressure (mmHg) | -1.7 mmHg | Standard Deviation 12.06 |
Secondary
Change From to Baseline of Bilirubin, Creatinin
Safety assessments by evaluating change from baseline of Bilirubin, Creatinin as per the study schedule
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all subjects who received at least one injection with study medication and have data available for the respective visit. Participants were analyzed as treated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Change From to Baseline of Bilirubin, Creatinin | Week 4 of cycle 1 - Creatinine (μmol/L) | 0.52 μmol/L | Standard Deviation 8.404 |
| Botulinum Toxin A | Change From to Baseline of Bilirubin, Creatinin | Week 4 of cycle 1 - Bilirubin (μmol/L) | 0.05 μmol/L | Standard Deviation 3.555 |
| Placebo | Change From to Baseline of Bilirubin, Creatinin | Week 4 of cycle 1 - Creatinine (μmol/L) | -0.30 μmol/L | Standard Deviation 6.556 |
| Placebo | Change From to Baseline of Bilirubin, Creatinin | Week 4 of cycle 1 - Bilirubin (μmol/L) | -0.14 μmol/L | Standard Deviation 3.597 |
| Botulinum Toxin A Open Label Extension Arm | Change From to Baseline of Bilirubin, Creatinin | Week 4 of cycle 3 - Creatinine (μmol/L) | 0.06 μmol/L | Standard Deviation 9.553 |
| Botulinum Toxin A Open Label Extension Arm | Change From to Baseline of Bilirubin, Creatinin | Week 4 of cycle 4 - Bilirubin (μmol/L) | 0.52 μmol/L | Standard Deviation 3.203 |
| Botulinum Toxin A Open Label Extension Arm | Change From to Baseline of Bilirubin, Creatinin | Week 4 of cycle 4 - Creatinine (μmol/L) | -0.66 μmol/L | Standard Deviation 9.536 |
| Botulinum Toxin A Open Label Extension Arm | Change From to Baseline of Bilirubin, Creatinin | Week 4 of cycle 2 - Bilirubin (μmol/L) | -0.12 μmol/L | Standard Deviation 3.329 |
| Botulinum Toxin A Open Label Extension Arm | Change From to Baseline of Bilirubin, Creatinin | Week 4 of cycle 2 - Creatinine (μmol/L) | -0.49 μmol/L | Standard Deviation 8.55 |
| Botulinum Toxin A Open Label Extension Arm | Change From to Baseline of Bilirubin, Creatinin | Week 4 of cycle 3 - Bilirubin (μmol/L) | -0.14 μmol/L | Standard Deviation 3.283 |
Secondary
Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines)
Extent of change in psychological impact at week 4 after first treatment, relative to baseline, assessed by * modified Skindex-16 (Glabellar Line Quality of Life Scale, \[GL-QoL\]): Each of 7 items rated on 5-point scale: 0/Never, 1/Rarely, 2/Sometimes, 3/Often, 4/Always bothered, than rescaled to a 0 to 100 standardized score; Emotional Domain is the mean of 4 of the items; Social Functioning Domain is the mean of 3 of the items; Overall score is the mean of all 7 items. All reported scores ranging from 0 (best outcome) to 100 (worst outcome). * validated FACE-Q Appraisal of Lines Between Eyebrows scale: Each of 7 items rated on 4-point scale: 1/Not at all, 2/a little, 3/moderately, 4/extremely. Reported score is the sum of the 7 items, standardized on a scale from 0 (worst outcome) to 100 (best outcome). * Age Appraisal visual analog scale \[VAS\]: Perception of Age compared to actual age, in years ranging from -15 years (best outcome) to +15 years (worst outcome).
Time frame: Week 4
Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Botulinum Toxin A | Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | Modified Skindex-16 (GL-QoL) Social Functioning domain - Change from Baseline at Week 4 | -33.14 score on a scale | Standard Deviation 33.193 |
| Botulinum Toxin A | Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | FACE-Q Appraisal of Lines Between Eyebrows - Change from Baseline at Week 4 | 46.4 score on a scale | Standard Deviation 28.62 |
| Botulinum Toxin A | Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | Modified Skindex-16 (GL-QoL) Overall score - Change from Baseline at Week 4 | -38.35 score on a scale | Standard Deviation 31.075 |
| Botulinum Toxin A | Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | Age Appraisal VAS - Change from Baseline at Week 4 | -2.3 score on a scale | Standard Deviation 4.2 |
| Botulinum Toxin A | Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | Modified Skindex-16 (GL-QoL) Emotional domain - Change from Baseline at Week 4 | -42.27 score on a scale | Standard Deviation 34.484 |
| Placebo | Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | Age Appraisal VAS - Change from Baseline at Week 4 | -0.2 score on a scale | Standard Deviation 3.42 |
| Placebo | Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | Modified Skindex-16 (GL-QoL) Emotional domain - Change from Baseline at Week 4 | 0.50 score on a scale | Standard Deviation 20.427 |
| Placebo | Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | Modified Skindex-16 (GL-QoL) Social Functioning domain - Change from Baseline at Week 4 | -2.23 score on a scale | Standard Deviation 31.088 |
| Placebo | Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | Modified Skindex-16 (GL-QoL) Overall score - Change from Baseline at Week 4 | -0.67 score on a scale | Standard Deviation 22.369 |
| Placebo | Extent of Change in Psychological Impact (Emotional and Social Functioning and Concerns Relating to Glabellar Lines) | FACE-Q Appraisal of Lines Between Eyebrows - Change from Baseline at Week 4 | -2.9 score on a scale | Standard Deviation 21.6 |
Comparison: Test performed for Modified Skindex-16 (GL-QoL) Emotional domain - Change from Baseline at Week 4p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Test performed for Modified Skindex-16 (GL-QoL) Social Functioning domain - Change from Baseline at Week 4p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Test performed for Modified Skindex-16 (GL-QoL) Overall score - Change from Baseline at Week 4.p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Test performed for FACE-Q Appraisal of Lines Between Eyebrows - Change from Baseline at Week 4p-value: <0.001Wilcoxon (Mann-Whitney)
Comparison: Test performed for FACE-Q Age Appraisal VAS scorep-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
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.
The 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, based on both the investigator's and the subject's in-clinic assessments (composite endpoint). 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.
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin 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. | Week 4 after 1st Re-treatment | 153 Participants |
| Botulinum Toxin 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. | Week 4 after 2nd Re-treatment | 119 Participants |
| Botulinum Toxin 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. | Week 4 after 3rd Re-treatment | 43 Participants |
Secondary
Number of Participants With Neutralizing Anti-Drug Antibodies
Number of Participants with Neutralizing Anti-Drug Antibodies Antibody formation, evaluation pre-dose before each treatment, at 4 weeks after each treatment and at the final study visit.
Time frame: Through study completion (60 weeks)
Population: The population used consists of all subjects who received at least one injection with study medication. Participants were analyzed as treated. Confirmation assays have only been performed for subjects with a reactive Screening Assay result.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | Number of Participants With Neutralizing Anti-Drug Antibodies | End of Study - ADA Screening Assay - Reactive | 0 Participants |
| Botulinum Toxin A | Number of Participants With Neutralizing Anti-Drug Antibodies | Baseline - Anti-Drug Antibodies (ADA) Screening Assay - Reactive | 23 Participants |
| Botulinum Toxin A | Number of Participants With Neutralizing Anti-Drug Antibodies | End of Study - ADA Confirmation Assay - Confirmed | 0 Participants |
| Botulinum Toxin A | Number of Participants With Neutralizing Anti-Drug Antibodies | Baseline - ADA Confirmation Assay - Confirmed | 0 Participants |
| Placebo | Number of Participants With Neutralizing Anti-Drug Antibodies | End of Study - ADA Screening Assay - Reactive | 0 Participants |
| Placebo | Number of Participants With Neutralizing Anti-Drug Antibodies | Baseline - Anti-Drug Antibodies (ADA) Screening Assay - Reactive | 4 Participants |
| Placebo | Number of Participants With Neutralizing Anti-Drug Antibodies | Baseline - ADA Confirmation Assay - Confirmed | 0 Participants |
| Placebo | Number of Participants With Neutralizing Anti-Drug Antibodies | End of Study - ADA Confirmation Assay - Confirmed | 0 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Neutralizing Anti-Drug Antibodies | End of Study - ADA Confirmation Assay - Confirmed | 0 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Neutralizing Anti-Drug Antibodies | End of Study - ADA Screening Assay - Reactive | 21 Participants |
Secondary
Number of Participants With Normal and Abnormal Electrocardiogram
Safety assessments by evaluating Electrocardiogram as per the study schedule
Time frame: Week 4 and last visit of Treatment Cycle 1 (End of Cycle procedures), conducted upon confirmation of eligibility for retreatment, assessed starting 12 weeks post-treatment with 4-weekly evaluations up to a max. of 48 weeks post treatment.
Population: The population used consists of all subjects who received at least one injection with study medication and who have data available for the respective visit and category of baseline electrocardiogram interpretation. Participants were analyzed as treated.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Botulinum Toxin A | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 Week 4 - Electrocardiogram Interpretation | Normal | 223 Participants |
| Botulinum Toxin A | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 Week 4 - Electrocardiogram Interpretation | Abnormal | 13 Participants |
| Botulinum Toxin A | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation | Normal | 198 Participants |
| Botulinum Toxin A | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation | Abnormal | 10 Participants |
| Placebo | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation | Abnormal | 19 Participants |
| Placebo | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation | Normal | 6 Participants |
| Placebo | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 Week 4 - Electrocardiogram Interpretation | Abnormal | 22 Participants |
| Placebo | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 Week 4 - Electrocardiogram Interpretation | Normal | 5 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation | Abnormal | 4 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 Week 4 - Electrocardiogram Interpretation | Abnormal | 3 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation | Normal | 69 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 Week 4 - Electrocardiogram Interpretation | Normal | 71 Participants |
| Placebo - Abnormal Baseline Electrocardiogram Interpretation | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation | Abnormal | 8 Participants |
| Placebo - Abnormal Baseline Electrocardiogram Interpretation | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 Week 4 - Electrocardiogram Interpretation | Abnormal | 8 Participants |
| Placebo - Abnormal Baseline Electrocardiogram Interpretation | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 Week 4 - Electrocardiogram Interpretation | Normal | 3 Participants |
| Placebo - Abnormal Baseline Electrocardiogram Interpretation | Number of Participants With Normal and Abnormal Electrocardiogram | Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation | Normal | 3 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs)
Number of Participants with treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest (AESIs)
Time frame: Through study completion (60 weeks)
Population: The population used consists of all subjects who received at least one injection with study medication. Participants were analyzed as treated.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Treatment Emergent Adverse Event (TEAE) | 48 Participants |
| Botulinum Toxin A | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Injection Procedure Related TEAE | 4 Participants |
| Botulinum Toxin A | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Severe TEAE | 1 Participants |
| Botulinum Toxin A | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with severe study drug related TEAE | 0 Participants |
| Botulinum Toxin A | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with severe injection procedure related TEAE | 0 Participants |
| Botulinum Toxin A | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Serious TEAE | 1 Participants |
| Botulinum Toxin A | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Adverse Events of Special Interest (AESI) | 1 Participants |
| Botulinum Toxin A | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any TEAE leading to discontinuation | 0 Participants |
| Botulinum Toxin A | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Study Medication Related TEAE | 4 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Serious TEAE | 1 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Treatment Emergent Adverse Event (TEAE) | 14 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with severe injection procedure related TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Severe TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Injection Procedure Related TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Study Medication Related TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any TEAE leading to discontinuation | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Adverse Events of Special Interest (AESI) | 0 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with severe study drug related TEAE | 0 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Adverse Events of Special Interest (AESI) | 7 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Severe TEAE | 3 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with severe injection procedure related TEAE | 0 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Serious TEAE | 4 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Study Medication Related TEAE | 8 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with severe study drug related TEAE | 0 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Treatment Emergent Adverse Event (TEAE) | 80 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any Injection Procedure Related TEAE | 6 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Subjects with any TEAE leading to discontinuation | 0 Participants |
Secondary
Percentage of Responders at Maximum Frown at Week 12
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 12 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. 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.
Time frame: Week 12
Population: The population used consists of all randomized subjects, regardless of whether they received study medication. Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale (FWS) at baseline or week 12 were assigned as being non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Botulinum Toxin A | Percentage of Responders at Maximum Frown at Week 12 | 56 Participants |
| Placebo | Percentage of Responders at Maximum Frown at Week 12 | 1 Participants |
Secondary
Percentage of Responders at Week 16
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 16 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. 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.
Time frame: Week 16
Population: The population used consists of all randomized subjects for whom data are available for week 16 or who were re-treated before week 16. They were analyzed as randomized and participants who were re-treated before week 16 were counted as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Botulinum Toxin A | Percentage of Responders at Week 16 | 27 Participants |
| Placebo | Percentage of Responders at Week 16 | 1 Participants |
Secondary
Percentage of Responders at Week 20
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 20 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. 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.
Time frame: Week 20
Population: The population used consists of all randomized subjects for whom data are available for week 20 or who were re-treated before week 20. They were analyzed as randomized and participants who were re-treated before week 20 were counted as non-responders.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Botulinum Toxin A | Percentage of Responders at Week 20 | 5 Participants |
| Placebo | Percentage of Responders at Week 20 | 0 Participants |
Secondary
Responder Rate at Weeks 1, 2 and 8
The Percentage of responders among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score at maximum frown of 0 or 1 and an improvement ≥ 2 points in FWS score (at maximum frown) during the first treatment cycle visit relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint, at weeks 1, 2 and 8). 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.
Time frame: Week 1, Week 2 and Week 8
Population: The population used consists of all randomized subjects, regardless of whether they received study medication. Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale (FWS) at baseline or at the respective visit were assigned as being non-responders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | Responder Rate at Weeks 1, 2 and 8 | Week 1 | 150 Participants |
| Botulinum Toxin A | Responder Rate at Weeks 1, 2 and 8 | Week 2 | 189 Participants |
| Botulinum Toxin A | Responder Rate at Weeks 1, 2 and 8 | Week 8 | 129 Participants |
| Placebo | Responder Rate at Weeks 1, 2 and 8 | Week 1 | 0 Participants |
| Placebo | Responder Rate at Weeks 1, 2 and 8 | Week 2 | 0 Participants |
| Placebo | Responder Rate at Weeks 1, 2 and 8 | Week 8 | 0 Participants |
Secondary
Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale.
The extent of subject perceptions of effect of, and satisfaction with, treatment in the BoNT/A-DP and placebo groups, during each treatment cycle, as assessed by the validated FACE-Q Satisfaction with Outcome Scale. The FACE-Q Satisfaction with Outcome scale is a patient-reported outcome measure designed to assess a patient's satisfaction with the results of a facial aesthetic procedure. This scale comprises six items, each with four response options: definitely agree, somewhat agree, somewhat disagree, and definitely disagree.
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all randomized subjects who were treated in the respective study cycle and treatment group. Participants were analyzed as randomized.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - miraculous | Somewhat disagree | 46 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - look in the mirror | Missing | 2 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - miraculous | Somewhat agree | 88 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - great | Somewhat agree | 58 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - miraculous | Definitely agree | 99 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - fantastic | Definitely disagree | 25 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - miraculous | Missing | 2 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - look in the mirror | Somewhat disagree | 34 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - pleased | Definitely disagree | 16 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - fantastic | Somewhat disagree | 31 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - pleased | Somewhat disagree | 13 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - great | Missing | 2 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - pleased | Somewhat agree | 46 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - fantastic | Somewhat agree | 74 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - pleased | Definitely agree | 189 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - look in the mirror | Somewhat agree | 101 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - pleased | Missing | 2 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - fantastic | Definitely agree | 134 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - expected | Definitely disagree | 17 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - great | Definitely agree | 163 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - expected | Somewhat disagree | 27 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - fantastic | Missing | 2 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - expected | Somewhat agree | 69 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - look in the mirror | Definitely agree | 111 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - expected | Definitely agree | 151 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - miraculous | Definitely disagree | 31 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - expected | Missing | 2 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - look in the mirror | Definitely disagree | 18 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - great | Definitely disagree | 23 Participants |
| Botulinum Toxin A | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - great | Somewhat disagree | 20 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - great | Definitely disagree | 77 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - great | Somewhat disagree | 7 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - great | Somewhat agree | 2 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - great | Definitely agree | 0 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - great | Missing | 3 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - look in the mirror | Definitely disagree | 74 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - look in the mirror | Somewhat disagree | 10 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - look in the mirror | Somewhat agree | 2 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - look in the mirror | Definitely agree | 0 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - look in the mirror | Missing | 3 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - fantastic | Definitely disagree | 78 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - fantastic | Somewhat disagree | 7 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - fantastic | Somewhat agree | 1 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - fantastic | Definitely agree | 0 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - fantastic | Missing | 3 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - miraculous | Definitely disagree | 78 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - miraculous | Somewhat disagree | 8 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - miraculous | Somewhat agree | 0 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - miraculous | Definitely agree | 0 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - miraculous | Missing | 3 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - pleased | Definitely disagree | 78 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - pleased | Somewhat disagree | 3 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - pleased | Somewhat agree | 4 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - pleased | Definitely agree | 1 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - pleased | Missing | 3 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - expected | Definitely disagree | 74 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - expected | Somewhat disagree | 7 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - expected | Somewhat agree | 5 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - expected | Definitely agree | 0 Participants |
| Placebo | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 1 Week 4 - expected | Missing | 3 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - miraculous | Somewhat agree | 77 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - miraculous | Definitely agree | 98 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - miraculous | Missing | 4 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - pleased | Definitely disagree | 12 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - pleased | Somewhat disagree | 6 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - pleased | Somewhat agree | 37 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - pleased | Definitely agree | 83 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - expected | Definitely disagree | 10 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - expected | Somewhat disagree | 17 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - expected | Somewhat agree | 34 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - expected | Missing | 1 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - great | Definitely disagree | 17 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - great | Somewhat disagree | 16 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - great | Definitely agree | 72 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - great | Missing | 1 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - look in the mirror | Definitely disagree | 15 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - look in the mirror | Somewhat disagree | 18 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - look in the mirror | Somewhat agree | 55 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - look in the mirror | Definitely agree | 50 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - look in the mirror | Missing | 1 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - fantastic | Definitely disagree | 21 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - fantastic | Somewhat disagree | 16 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - fantastic | Somewhat agree | 46 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - fantastic | Definitely agree | 55 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - fantastic | Missing | 1 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - miraculous | Definitely disagree | 29 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - miraculous | Somewhat disagree | 23 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - miraculous | Somewhat agree | 45 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - miraculous | Definitely agree | 41 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - look in the mirror | Definitely disagree | 26 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - miraculous | Missing | 1 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - look in the mirror | Somewhat disagree | 31 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - look in the mirror | Somewhat agree | 100 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - look in the mirror | Definitely agree | 104 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - look in the mirror | Missing | 4 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - fantastic | Definitely disagree | 35 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - fantastic | Somewhat disagree | 31 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - fantastic | Somewhat agree | 72 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - pleased | Definitely disagree | 17 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - pleased | Somewhat disagree | 20 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - pleased | Somewhat agree | 75 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - pleased | Definitely agree | 200 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - pleased | Missing | 11 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - expected | Definitely disagree | 24 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - expected | Somewhat disagree | 34 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - expected | Somewhat agree | 78 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - great | Somewhat disagree | 23 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - great | Somewhat agree | 80 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - great | Definitely agree | 179 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - miraculous | Somewhat agree | 105 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - pleased | Missing | 4 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - expected | Somewhat disagree | 23 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - expected | Missing | 4 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - great | Definitely disagree | 24 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - great | Somewhat agree | 56 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - great | Definitely agree | 151 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - pleased | Missing | 1 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - expected | Definitely agree | 77 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 4 Week 4 - great | Somewhat agree | 33 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - expected | Definitely agree | 176 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - expected | Missing | 11 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - great | Definitely disagree | 30 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - great | Missing | 11 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - look in the mirror | Definitely disagree | 25 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - look in the mirror | Somewhat disagree | 47 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - look in the mirror | Somewhat agree | 111 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - look in the mirror | Definitely agree | 129 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - look in the mirror | Missing | 11 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - fantastic | Definitely disagree | 36 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - fantastic | Somewhat disagree | 46 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - fantastic | Somewhat agree | 90 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - fantastic | Definitely agree | 140 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - fantastic | Missing | 11 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - miraculous | Definitely disagree | 52 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - miraculous | Somewhat disagree | 53 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - miraculous | Definitely agree | 102 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 2 Week 4 - miraculous | Missing | 11 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - pleased | Definitely disagree | 16 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - pleased | Somewhat disagree | 19 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - pleased | Somewhat agree | 60 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - pleased | Definitely agree | 166 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - expected | Definitely disagree | 20 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - expected | Somewhat agree | 62 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - expected | Definitely agree | 156 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - great | Somewhat disagree | 30 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - great | Missing | 4 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - fantastic | Definitely agree | 123 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - fantastic | Missing | 4 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - miraculous | Definitely disagree | 52 Participants |
| Botulinum Toxin A Open Label Extension Arm | Satisfaction With Treatment, During Each Treatment Cycle, as Assessed by the Validated FACE-Q Satisfaction With Outcome Scale. | Cycle 3 Week 4 - miraculous | Somewhat disagree | 34 Participants |
Secondary
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During Each Re-treatment Cycle at Week 4 Relative to Re-treatment-baseline.
The percentage of subjects with ≥ 1-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP during each re-treatment cycle at week 4 relative to re-treatment baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). 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.
Time frame: Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56)
Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During Each Re-treatment Cycle at Week 4 Relative to Re-treatment-baseline. | Week 4 after 1st Re-treatment | 267 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During Each Re-treatment Cycle at Week 4 Relative to Re-treatment-baseline. | Week 4 after 2nd Re-treatment | 210 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During Each Re-treatment Cycle at Week 4 Relative to Re-treatment-baseline. | Week 4 after 3rd Re-treatment | 104 Participants |
Secondary
The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline
The percentage of subjects with ≥ 1-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle at week 1, 2, 4, 8, 12, 16 and 20 relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). For week 16 and 20 subjects who were re-treated before the respective visits were counted as non-responders. 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.
Time frame: Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 of Treatment Cycle 1
Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 1 | 220 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 2 | 234 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 4 | 236 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 8 | 213 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 12 | 162 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 16 | 94 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 20 | 46 Participants |
| Placebo | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 20 | 0 Participants |
| Placebo | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 1 | 2 Participants |
| Placebo | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 12 | 2 Participants |
| Placebo | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 2 | 0 Participants |
| Placebo | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 4 | 0 Participants |
| Placebo | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 16 | 1 Participants |
| Placebo | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | Week 8 | 1 Participants |
Secondary
The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown)
The percentage of subjects with ≥ 2-point and ≥ 1 reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle visit relative to baseline, based on the independent rater's assessment of photographs (at baseline and visits 2, 4, 12, 16 and 20 weeks after treatment, within the first treatment cycle). The median value of all assessments of the same photography was considered for analysis. 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.
Time frame: Week 2, 4, 12, 16 and 20
Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 2-point reduction - Week 16 | 4 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 1-point reduction - Week 4 | 234 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 2-point reduction - Week 12 | 11 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 1-point reduction - Week 12 | 71 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 2-point reduction - Week 20 | 2 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 1-point reduction - Week 16 | 29 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 2-point reduction - Week 4 | 144 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 1-point reduction - Week 20 | 21 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 1-point reduction - Week 2 | 235 Participants |
| Botulinum Toxin A | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 2-point reduction - Week 2 | 150 Participants |
| Placebo | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 1-point reduction - Week 2 | 6 Participants |
| Placebo | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 2-point reduction - Week 4 | 0 Participants |
| Placebo | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 2-point reduction - Week 12 | 1 Participants |
| Placebo | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 2-point reduction - Week 16 | 0 Participants |
| Placebo | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 2-point reduction - Week 20 | 0 Participants |
| Placebo | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 2-point reduction - Week 2 | 0 Participants |
| Placebo | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 1-point reduction - Week 4 | 9 Participants |
| Placebo | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 1-point reduction - Week 12 | 5 Participants |
| Placebo | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 1-point reduction - Week 16 | 0 Participants |
| Placebo | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | ≥ 1-point reduction - Week 20 | 1 Participants |
Secondary
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
The Percentage of subjects with a ≥ 1 point reduction in Facial Wrinkle Scale (FWS) score at rest at week 4 in the first treatment cycle, based separately on the investigators' and the subjects' in-clinic assessments (applicable only for subjects who have a FWS score at rest ≥ 1 at baseline). 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.
Time frame: Week 4
Population: The population used consists of all randomized subjects with a Facial Wrinkle Scale (FWS) score at rest \>=1 at baseline. Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale at week 4 were assigned as being non-responders.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | 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 | Subject's In-clinic Assessment | 214 Participants |
| Botulinum Toxin A | 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 | Investigator's In-clinic Assessment | 163 Participants |
| Placebo | 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 | Investigator's In-clinic Assessment | 8 Participants |
| Placebo | 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 | Subject's In-clinic Assessment | 11 Participants |
Secondary
The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos.
The percentage of subjects with a ≥ 1 point reduction in Facial Wrinkle Scale (FWS) score at rest in the BoNT/A-DP and placebo groups, relative to baseline, during the first treatment cycle, based on the independent rater's assessment of photos. The median value of all assessments of the same photography was considered for analysis. 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.
Time frame: Week 2, Week 4, Week 12, Week 16, Week 20 of Treatment Cycle 1
Population: The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 4 | 100 Participants |
| Botulinum Toxin A | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 16 | 21 Participants |
| Botulinum Toxin A | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 12 | 37 Participants |
| Botulinum Toxin A | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 2 | 106 Participants |
| Botulinum Toxin A | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 20 | 11 Participants |
| Placebo | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 20 | 1 Participants |
| Placebo | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 2 | 9 Participants |
| Placebo | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 4 | 13 Participants |
| Placebo | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 12 | 8 Participants |
| Placebo | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | Week 16 | 0 Participants |
Secondary
Time to Onset of Effect in the BoNT/A-DP and Placebo Groups in the First Treatment Cycle
Time to onset of effect in the BoNT/A-DP and placebo groups in the first treatment cycle, as measured at weeks 1, 2 and 4 based separately on subject and investigator assessment. Onset of effect defined as at least a 1 point improvement in Facial Wrinkle Scale (FWS) score from baseline (at maximum frown). 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.
Time frame: From treatment at Day 0 to Week 4 in Treatment Cycle 1
Population: The population used consists of all randomized subjects. Participants were analyzed as randomized.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Botulinum Toxin A | Time to Onset of Effect in the BoNT/A-DP and Placebo Groups in the First Treatment Cycle | 8 Days |
| Placebo | Time to Onset of Effect in the BoNT/A-DP and Placebo Groups in the First Treatment Cycle | NA Days |