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
This multicenter Phase 3 study is comprised of two parts. The first part of the study is a randomized, double blind, placebo-controlled, phase which aims to demonstrate efficacy and safety of BoNT/A-DP compared with placebo. The second part is an open label extension phase to evaluate efficacy after repeat treatments and long term safety. Subjects can receive a maximum of four treatment cycles over the duration of the study, a single treatment in the first cycle compared with placebo, and up to three subsequent treatments in the open label extension study.
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
DRUGBotulinum Toxin A - Open Label
Open Label Extension Phase with Experimental Drug; Injection, 20 Units 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
* Aged ≥ 18 years or older at time of screening on FWS) as determined by in-clinic assessments by both the investigator and the subject(where: 0= 'none', 1= 'mild', 2= 'moderate', 3= 'severe'). * Subject has a stable medical condition with no uncontrolled systemic disease. * Female subjects of childbearing potential must test negative for pregnancy and agree to use effective birth control during the course of the study. * Subjects who wear glasses must be able to adequately self-assess the severity of their glabellar lines (according to the FWS), without glasses obstructing the forehead area. * The moderate to severe glabellar lines have an important psychological impact on the subject, as indicated by scores \>0 on either the Emotional or the Social Functioning subscale of the modified Skindex-16 (GL-QoL).
Exclusion criteria
* Previous treatment with any serotype of botulinum toxin for any indication within the 12 months prior to screening, or any planned treatment with botulinum toxin of any serotype for any reason during the trial (other than the investigational treatment). * Known hypersensitivity to the study medication or its excipients. * Any medical condition that may place the subject at increased risk due to exposure to botulinum toxin, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis, profound atrophy or weakness in the target muscles, or any other condition (at the investigator's discretion) that might interfere with neuromuscular function or contraindicate botulinum toxin therapy. * Facial laser or light treatment, microdermabrasion, superficial peels or retinoid therapy within the 3 months prior to screening or planned during the study. * Apart from the procedures specified above, previous treatment with any facial aesthetic procedure in the glabellar area (including chemical peeling, injection with biodegradable fillers,) within 12 months prior to screening or planned during the study. * Previous insertion of permanent material in the glabellar area or planned during the study. * Any surgery, or history of surgery, in the glabellar area including surgical removal of the corrugator, procerus or depressor supercili muscles or a combination of these, or scars in the glabellar area, or such surgery planned during the study. * Active skin disease/infection or irritation at the treatment area. * Inability to substantially lessen glabellar frown lines even by physically spreading them apart. * Use of a muscle relaxant, , within 2 weeks prior to screening or planned during the study. * Marked facial asymmetry or ptosis of eyelid and/or eyebrow, or current facial palsy or neuromuscular junction disorders as judged by the investigator. * Pregnant, breastfeeding or planning to become pregnant during the trial. * Use of prohibited medication including anticholinergic drugs, or drugs which could interfere with neuromuscular function, including aminoglycoside antibiotics and curare-like compounds within 2 weeks prior to screening or planned during the study. * Planned surgery with general anaesthetic (use of local anaesthetic outside the glabellar area is permitted). * Participation in another clinical study within one month of screening and throughout the trial. * Previous participation in another botulinum toxin aesthetic study which involved the treatment of glabellar lines in combination with canthal lines and/or forehead lines in the previous 18 months. * Chronic drug or alcohol abuse (as per investigator discretion). Eligibility Criteria for re-treatment: The following criteria MUST be met for re-treatment: * At time of re-treatment subject does not have relevant changes to their health status from enrollment, which would have prevented subject's entry into the study according to the inclusion and
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 |
|---|---|---|
| Percentage of Responders at Maximum Frown 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. |
| 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. |
| Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 | Week 20, Week 24, Week 28, Week 32 | 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 the respective 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. |
| 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 Weeks 1, 2 and 8 | Week 1, Week 2, 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. |
| Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 2, Week 4, Week 12, Week 16, Week 20 | The percentage of subjects with ≥ 2-point 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 raters' 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 | Week 4 of Treatment Cycles 1, 2, 3 and 4 | 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. |
| Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 2, Week 4, Week 12, Week 16, Week 20, Week 24, Week 28 | 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 raters' assessment of photographs. 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. |
| 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 | Week 4 of Treatment Cycles 2, 3 and 4 | 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 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. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Through study completion (60 weeks) | Frequency, severity and causal relationship of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) during the entire study period. |
| 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. |
| Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle | Safety assessments by evaluating change from baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase as per the study schedule |
| Change From Baseline of Bilirubin, Creatinine | Week 4 of each treatment cycle | Safety assessments by evaluating change from baseline of Bilirubin, Creatinine as per the study schedule as change from baseline |
| Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle | Safety assessments by evaluating change from baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen as per the study schedule |
| Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle | Safety assessments by evaluating change from baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets as per the study schedule |
| Change From Baseline of Erythrocytes | Week 4 of each treatment cycle | Safety assessments by evaluating change from baseline of Erythrocytes as per the study schedule |
| Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of each treatment cycle | Safety assessments by evaluating change from baseline of Erythrocyte MCHC, Hemoglobin as per the study schedule |
| Change From Baseline of of Erythrocyte MCV | Week 4 of each treatment cycle | Safety assessments by evaluating change from baseline of Erythrocyte MCV as per the study schedule |
| Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle | Safety assessments by evaluating change from baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes as per the study schedule as change from baseline |
| Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of Treatment Cycles 1, 2, 3 and 4 | Safety assessments by evaluating change from baseline of Systolic and Diastolic Blood Pressure as per the study schedule |
| Change From Baseline of Pulse Rate | Week 4 of Treatment Cycles 1, 2, 3 and 4 | Safety assessments by evaluating change from baseline of Pulse rate as per the study schedule |
| Number of Participants With Normal and Abnormal Electrocardiogram | Last visit of Treatment Cycle 1 (End of Cycle procedures) conducted upon confirmation of eligibility for retreatment, which was assessed starting 12 weeks post-treatment with 4-weekly evaluations up to a maximum of 48 weeks post treatment. | Safety assessments by evaluating Electrocardiogram as per the study schedule |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
Of 251 enrolled participants, 213 met inclusion criteria and were randomized to treatment.
Participants by arm
| Arm | Count |
|---|---|
| Botulinum Toxin A Botulinum Toxin A (Clostridium botulinum toxin type A) will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area.
Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m. injections into the glabellar area | 160 |
| Placebo Placebo will be administered in double blind fashion in cycle 1. divided in five 0.1 mL i.m. injections into the glabellar area.
Placebo: Injection, sodium chloride 0.9 % divided in five 0.1 mL i.m. injections into glabellar area | 53 |
| Total | 213 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double Blind Phase | Lost to Follow-up | 8 | 3 | 0 |
| Double Blind Phase | Withdrawal by Subject | 5 | 2 | 0 |
| Open Label Phase | Lost to Follow-up | 0 | 0 | 10 |
| Open Label Phase | Withdrawal by Subject | 0 | 0 | 6 |
Baseline characteristics
| Characteristic | Botulinum Toxin A | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 19 Participants | 8 Participants | 27 Participants |
| Age, Categorical Between 18 and 65 years | 141 Participants | 45 Participants | 186 Participants |
| Age, Continuous | 52.04 years STANDARD_DEVIATION 10.458 | 52.43 years STANDARD_DEVIATION 10.137 | 52.14 years STANDARD_DEVIATION 10.357 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 33 Participants | 7 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 126 Participants | 45 Participants | 171 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 2 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 | 48 Participants | 16 Participants | 64 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 | 112 Participants | 37 Participants | 149 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 | 39 Participants | 11 Participants | 50 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 | 121 Participants | 42 Participants | 163 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 153 Participants | 50 Participants | 203 Participants |
| Region of Enrollment United States | 160 Participants | 53 Participants | 213 Participants |
| Sex: Female, Male Female | 150 Participants | 45 Participants | 195 Participants |
| Sex: Female, Male Male | 10 Participants | 8 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 160 | 0 / 53 | 0 / 195 |
| other Total, other adverse events | 12 / 160 | 2 / 53 | 18 / 195 |
| serious Total, serious adverse events | 0 / 160 | 0 / 53 | 2 / 195 |
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 who received at least one injection with 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 | 78 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 | 1 Participants |
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase
Safety assessments by evaluating change from baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase as per the study schedule
Time frame: Week 4 of each treatment cycle
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 Transferase | Week 4 of each treatment cycle - Alanine Aminotransferase (U/L) | 0.47 U/L | Standard Deviation 7.939 |
| Botulinum Toxin A | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Alkaline Phosphatase (U/L) | -0.16 U/L | Standard Deviation 8.174 |
| Botulinum Toxin A | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Aspartate Aminotransferase (U/L) | 0.07 U/L | Standard Deviation 11.156 |
| Botulinum Toxin A | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Gamma Glutamyl Transferase (U/L) | 0.69 U/L | Standard Deviation 7.418 |
| Placebo | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Alanine Aminotransferase (U/L) | 1.33 U/L | Standard Deviation 19.151 |
| Placebo | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Gamma Glutamyl Transferase (U/L) | 4.31 U/L | Standard Deviation 16.315 |
| Placebo | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Alkaline Phosphatase (U/L) | 1.50 U/L | Standard Deviation 8.989 |
| Placebo | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Aspartate Aminotransferase (U/L) | 2.39 U/L | Standard Deviation 11.206 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Gamma Glutamyl Transferase (U/L) | 0.86 U/L | Standard Deviation 8.245 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Alkaline Phosphatase (U/L) | 1.18 U/L | Standard Deviation 7.898 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Aspartate Aminotransferase (U/L) | -0.43 U/L | Standard Deviation 10.539 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Alanine Aminotransferase (U/L) | -0.07 U/L | Standard Deviation 9.132 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Alanine Aminotransferase (U/L) | 0.28 U/L | Standard Deviation 11.333 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Alkaline Phosphatase (U/L) | 1.15 U/L | Standard Deviation 9.704 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Gamma Glutamyl Transferase (U/L) | 2.15 U/L | Standard Deviation 16.974 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Aspartate Aminotransferase (U/L) | -0.85 U/L | Standard Deviation 12.249 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Gamma Glutamyl Transferase (U/L) | -0.48 U/L | Standard Deviation 8.998 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Aspartate Aminotransferase (U/L) | 0.56 U/L | Standard Deviation 8.055 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Alkaline Phosphatase (U/L) | -0.53 U/L | Standard Deviation 8.414 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase | Week 4 of each treatment cycle - Alanine Aminotransferase (U/L) | 0.93 U/L | Standard Deviation 8.528 |
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: Week 4 of each treatment cycle
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 each treatment cycle - Basophils (x10^9 cells/L) | 0.01 x10^9 cells/L | Standard Deviation 0.027 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Platelets (x10^9 cells/L) | -3.85 x10^9 cells/L | Standard Deviation 28.665 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Neutrophils (x10^9 cells/L) | -0.03 x10^9 cells/L | Standard Deviation 1.152 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Leukocytes (x10^9 cells/L) | -0.02 x10^9 cells/L | Standard Deviation 1.252 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Eosinophils (x10^9 cells/L) | 0.00 x10^9 cells/L | Standard Deviation 0.077 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Lymphocytes (x10^9 cells/L) | 0.01 x10^9 cells/L | Standard Deviation 0.369 |
| Botulinum Toxin A | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Monocytes (x10^9 cells/L) | -0.01 x10^9 cells/L | Standard Deviation 0.147 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Monocytes (x10^9 cells/L) | 0.00 x10^9 cells/L | Standard Deviation 0.141 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Lymphocytes (x10^9 cells/L) | -0.08 x10^9 cells/L | Standard Deviation 0.429 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Eosinophils (x10^9 cells/L) | 0.00 x10^9 cells/L | Standard Deviation 0.056 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Basophils (x10^9 cells/L) | 0.00 x10^9 cells/L | Standard Deviation 0.043 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Neutrophils (x10^9 cells/L) | -0.09 x10^9 cells/L | Standard Deviation 1.483 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Leukocytes (x10^9 cells/L) | -0.17 x10^9 cells/L | Standard Deviation 1.622 |
| Placebo | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Platelets (x10^9 cells/L) | 2.73 x10^9 cells/L | Standard Deviation 30.057 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Lymphocytes (x10^9 cells/L) | -0.02 x10^9 cells/L | Standard Deviation 0.36 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Basophils (x10^9 cells/L) | 0.00 x10^9 cells/L | Standard Deviation 0.031 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Eosinophils (x10^9 cells/L) | 0.01 x10^9 cells/L | Standard Deviation 0.06 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Leukocytes (x10^9 cells/L) | -0.01 x10^9 cells/L | Standard Deviation 1.303 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Monocytes (x10^9 cells/L) | 0.00 x10^9 cells/L | Standard Deviation 0.156 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Neutrophils (x10^9 cells/L) | 0.01 x10^9 cells/L | Standard Deviation 1.221 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Platelets (x10^9 cells/L) | 5.28 x10^9 cells/L | Standard Deviation 30.961 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Leukocytes (x10^9 cells/L) | 0.23 x10^9 cells/L | Standard Deviation 1.418 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Monocytes (x10^9 cells/L) | -0.01 x10^9 cells/L | Standard Deviation 0.127 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Eosinophils (x10^9 cells/L) | 0.03 x10^9 cells/L | Standard Deviation 0.084 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Platelets (x10^9 cells/L) | 12.08 x10^9 cells/L | Standard Deviation 32.635 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Neutrophils (x10^9 cells/L) | 0.17 x10^9 cells/L | Standard Deviation 1.29 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Basophils (x10^9 cells/L) | 0.00 x10^9 cells/L | Standard Deviation 0.043 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Lymphocytes (x10^9 cells/L) | 0.04 x10^9 cells/L | Standard Deviation 0.432 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Leukocytes (x10^9 cells/L) | -0.06 x10^9 cells/L | Standard Deviation 1.454 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Platelets (x10^9 cells/L) | 4.70 x10^9 cells/L | Standard Deviation 32.814 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Neutrophils (x10^9 cells/L) | -0.05 x10^9 cells/L | Standard Deviation 1.29 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Monocytes (x10^9 cells/L) | 0.00 x10^9 cells/L | Standard Deviation 0.149 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Eosinophils (x10^9 cells/L) | 0.01 x10^9 cells/L | Standard Deviation 0.109 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Basophils (x10^9 cells/L) | 0.00 x10^9 cells/L | Standard Deviation 0.035 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets | Week 4 of each treatment cycle - Lymphocytes (x10^9 cells/L) | -0.02 x10^9 cells/L | Standard Deviation 0.428 |
Secondary
Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes
Safety assessments by evaluating change from baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes as per the study schedule as change from baseline
Time frame: Week 4 of each treatment cycle
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/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Monocytes/Leukocytes (%) | -0.02 % of leukocytes | Standard Deviation 2.203 |
| Botulinum Toxin A | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Neutrophils/Leukocytes (%) | -0.64 % of leukocytes | Standard Deviation 7.095 |
| Botulinum Toxin A | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Eosinophils/Leukocytes (%) | 0.10 % of leukocytes | Standard Deviation 1.294 |
| Botulinum Toxin A | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Basophils/Leukocytes (%) | 0.15 % of leukocytes | Standard Deviation 0.472 |
| Botulinum Toxin A | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Lymphocytes/Leukocytes (%) | 0.42 % of leukocytes | Standard Deviation 6.185 |
| Placebo | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Monocytes/Leukocytes (%) | 0.24 % of leukocytes | Standard Deviation 1.923 |
| Placebo | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Lymphocytes/Leukocytes (%) | -0.22 % of leukocytes | Standard Deviation 6.856 |
| Placebo | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Basophils/Leukocytes (%) | 0.04 % of leukocytes | Standard Deviation 0.642 |
| Placebo | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Neutrophils/Leukocytes (%) | -0.04 % of leukocytes | Standard Deviation 8.037 |
| Placebo | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Eosinophils/Leukocytes (%) | -0.04 % of leukocytes | Standard Deviation 0.892 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Lymphocytes/Leukocytes (%) | -0.28 % of leukocytes | Standard Deviation 6.272 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Basophils/Leukocytes (%) | -0.08 % of leukocytes | Standard Deviation 0.57 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Eosinophils/Leukocytes (%) | 0.17 % of leukocytes | Standard Deviation 1.107 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Monocytes/Leukocytes (%) | -0.13 % of leukocytes | Standard Deviation 2.312 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Neutrophils/Leukocytes (%) | 0.32 % of leukocytes | Standard Deviation 7.605 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Neutrophils/Leukocytes (%) | 0.25 % of leukocytes | Standard Deviation 8.039 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Basophils/Leukocytes (%) | -0.03 % of leukocytes | Standard Deviation 0.636 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Monocytes/Leukocytes (%) | -0.40 % of leukocytes | Standard Deviation 1.927 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Lymphocytes/Leukocytes (%) | -0.25 % of leukocytes | Standard Deviation 6.927 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Eosinophils/Leukocytes (%) | 0.45 % of leukocytes | Standard Deviation 1.394 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Lymphocytes/Leukocytes (%) | 0.00 % of leukocytes | Standard Deviation 6.7 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Monocytes/Leukocytes (%) | 0.02 % of leukocytes | Standard Deviation 2.308 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Basophils/Leukocytes (%) | 0.03 % of leukocytes | Standard Deviation 0.568 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Neutrophils/Leukocytes (%) | -0.15 % of leukocytes | Standard Deviation 7.6 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Basophils/Leukocytes, Eosinophils/Leukocytes, Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes | Week 4 of each treatment cycle - Eosinophils/Leukocytes (%) | 0.13 % of leukocytes | Standard Deviation 1.336 |
Secondary
Change From Baseline of Bilirubin, Creatinine
Safety assessments by evaluating change from baseline of Bilirubin, Creatinine as per the study schedule as change from baseline
Time frame: Week 4 of each treatment cycle
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 Bilirubin, Creatinine | Week 4 of each treatment cycle - Bilirubin (μmol/L) | -0.54 μmol/L | Standard Deviation 3.233 |
| Botulinum Toxin A | Change From Baseline of Bilirubin, Creatinine | Week 4 of each treatment cycle - Creatinine (μmol/L) | 0.54 μmol/L | Standard Deviation 8.514 |
| Placebo | Change From Baseline of Bilirubin, Creatinine | Week 4 of each treatment cycle - Bilirubin (μmol/L) | 0.13 μmol/L | Standard Deviation 3.588 |
| Placebo | Change From Baseline of Bilirubin, Creatinine | Week 4 of each treatment cycle - Creatinine (μmol/L) | 1.07 μmol/L | Standard Deviation 6.487 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Bilirubin, Creatinine | Week 4 of each treatment cycle - Bilirubin (μmol/L) | 0.30 μmol/L | Standard Deviation 2.949 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Bilirubin, Creatinine | Week 4 of each treatment cycle - Creatinine (μmol/L) | -0.56 μmol/L | Standard Deviation 8.24 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Bilirubin, Creatinine | Week 4 of each treatment cycle - Creatinine (μmol/L) | -1.07 μmol/L | Standard Deviation 7.315 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Bilirubin, Creatinine | Week 4 of each treatment cycle - Bilirubin (μmol/L) | -0.16 μmol/L | Standard Deviation 3.494 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Bilirubin, Creatinine | Week 4 of each treatment cycle - Bilirubin (μmol/L) | 0.10 μmol/L | Standard Deviation 3.58 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Bilirubin, Creatinine | Week 4 of each treatment cycle - Creatinine (μmol/L) | -1.68 μmol/L | Standard Deviation 8.284 |
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: Week 4 of each treatment cycle
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 each treatment cycle - Sodium (mmol/L) | -0.10 mmol/L | Standard Deviation 2.101 |
| Botulinum Toxin A | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Cholesterol (mmol/L) | -0.06 mmol/L | Standard Deviation 0.559 |
| Botulinum Toxin A | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Urea Nitrogen (mmol/L) | -0.10 mmol/L | Standard Deviation 1.278 |
| Botulinum Toxin A | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Glucose (mmol/L) | 0.01 mmol/L | Standard Deviation 1.014 |
| Botulinum Toxin A | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Potassium (mmol/L) | -0.01 mmol/L | Standard Deviation 0.393 |
| Placebo | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Sodium (mmol/L) | 0.06 mmol/L | Standard Deviation 2.046 |
| Placebo | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Potassium (mmol/L) | 0.04 mmol/L | Standard Deviation 0.357 |
| Placebo | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Glucose (mmol/L) | -0.10 mmol/L | Standard Deviation 1.411 |
| Placebo | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Urea Nitrogen (mmol/L) | -0.40 mmol/L | Standard Deviation 1.327 |
| Placebo | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Cholesterol (mmol/L) | -0.03 mmol/L | Standard Deviation 0.473 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Potassium (mmol/L) | 0.04 mmol/L | Standard Deviation 0.376 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Cholesterol (mmol/L) | 0.03 mmol/L | Standard Deviation 0.533 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Glucose (mmol/L) | 0.11 mmol/L | Standard Deviation 1.339 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Sodium (mmol/L) | 0.26 mmol/L | Standard Deviation 1.939 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Urea Nitrogen (mmol/L) | -0.16 mmol/L | Standard Deviation 1.28 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Urea Nitrogen (mmol/L) | -0.13 mmol/L | Standard Deviation 1.41 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Cholesterol (mmol/L) | 0.00 mmol/L | Standard Deviation 0.594 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Sodium (mmol/L) | 0.31 mmol/L | Standard Deviation 2.021 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Potassium (mmol/L) | 0.03 mmol/L | Standard Deviation 0.395 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Glucose (mmol/L) | 0.22 mmol/L | Standard Deviation 1.133 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Potassium (mmol/L) | -0.03 mmol/L | Standard Deviation 0.365 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Sodium (mmol/L) | 0.26 mmol/L | Standard Deviation 1.959 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Cholesterol (mmol/L) | 0.01 mmol/L | Standard Deviation 0.615 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Urea Nitrogen (mmol/L) | -0.35 mmol/L | Standard Deviation 1.471 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Cholesterol, Glucose, Potassium, Sodium, Urea Nitrogen | Week 4 of each treatment cycle - Glucose (mmol/L) | 0.12 mmol/L | Standard Deviation 1.202 |
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: Week 4 of each treatment cycle
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 each treatment cycle - Erythrocyte MCHC(g/dL) | -0.28 g/dL | Standard Deviation 1.061 |
| Botulinum Toxin A | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of each treatment cycle - Hemoglobin (g/dL) | -0.07 g/dL | Standard Deviation 0.678 |
| Placebo | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of each treatment cycle - Erythrocyte MCHC(g/dL) | -0.15 g/dL | Standard Deviation 1.344 |
| Placebo | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of each treatment cycle - Hemoglobin (g/dL) | 0.22 g/dL | Standard Deviation 0.736 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of each treatment cycle - Erythrocyte MCHC(g/dL) | 0.30 g/dL | Standard Deviation 1.178 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of each treatment cycle - Hemoglobin (g/dL) | 0.04 g/dL | Standard Deviation 0.626 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of each treatment cycle - Hemoglobin (g/dL) | -0.09 g/dL | Standard Deviation 0.718 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of each treatment cycle - Erythrocyte MCHC(g/dL) | 0.06 g/dL | Standard Deviation 1.416 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of each treatment cycle - Erythrocyte MCHC(g/dL) | -0.62 g/dL | Standard Deviation 1.457 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Week 4 of each treatment cycle - Hemoglobin (g/dL) | -0.20 g/dL | Standard Deviation 0.656 |
Secondary
Change From Baseline of Erythrocytes
Safety assessments by evaluating change from baseline of Erythrocytes as per the study schedule
Time frame: Week 4 of each treatment cycle
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 | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Erythrocytes | -0.02 x10^12 cells/L | Standard Deviation 0.239 |
| Placebo | Change From Baseline of Erythrocytes | 0.05 x10^12 cells/L | Standard Deviation 0.246 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Erythrocytes | 0.01 x10^12 cells/L | Standard Deviation 0.203 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Erythrocytes | 0.01 x10^12 cells/L | Standard Deviation 0.214 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Erythrocytes | -0.03 x10^12 cells/L | Standard Deviation 0.201 |
Secondary
Change From Baseline of of Erythrocyte MCV
Safety assessments by evaluating change from baseline of Erythrocyte MCV as per the study schedule
Time frame: Week 4 of each treatment cycle
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 | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of of Erythrocyte MCV | 0.91 fL | Standard Deviation 2.633 |
| Placebo | Change From Baseline of of Erythrocyte MCV | 0.90 fL | Standard Deviation 4.121 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of of Erythrocyte MCV | -0.83 fL | Standard Deviation 3.408 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of of Erythrocyte MCV | -1.03 fL | Standard Deviation 4.307 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of of Erythrocyte MCV | 1.14 fL | Standard Deviation 4.747 |
Secondary
Change From Baseline of Pulse Rate
Safety assessments by evaluating change from baseline of Pulse rate as per the study schedule
Time frame: Week 4 of Treatment Cycles 1, 2, 3 and 4
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 | Value (MEAN) | Dispersion |
|---|---|---|---|
| Botulinum Toxin A | Change From Baseline of Pulse Rate | -2.48 bpm | Standard Deviation 10.165 |
| Placebo | Change From Baseline of Pulse Rate | -0.82 bpm | Standard Deviation 9.458 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Pulse Rate | 1.96 bpm | Standard Deviation 8.698 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Pulse Rate | 3.08 bpm | Standard Deviation 9.374 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Pulse Rate | 3.96 bpm | Standard Deviation 9.343 |
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: Week 4 of Treatment Cycles 1, 2, 3 and 4
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 each treatment cycle - Systolic Blood Pressure (mmHg) | -1.08 mmHg | Standard Deviation 13.027 |
| Botulinum Toxin A | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of each treatment cycle - Diastolic Blood Pressure (mmHg) | -2.48 mmHg | Standard Deviation 10.165 |
| Placebo | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of each treatment cycle - Systolic Blood Pressure (mmHg) | -0.59 mmHg | Standard Deviation 9.897 |
| Placebo | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of each treatment cycle - Diastolic Blood Pressure (mmHg) | -0.82 mmHg | Standard Deviation 9.458 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of each treatment cycle - Systolic Blood Pressure (mmHg) | 0.64 mmHg | Standard Deviation 13.15 |
| Botulinum Toxin A Open Label Extension Arm | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of each treatment cycle - Diastolic Blood Pressure (mmHg) | 1.96 mmHg | Standard Deviation 8.698 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of each treatment cycle - Diastolic Blood Pressure (mmHg) | 3.08 mmHg | Standard Deviation 9.374 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of each treatment cycle - Systolic Blood Pressure (mmHg) | -0.06 mmHg | Standard Deviation 14.91 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of each treatment cycle - Systolic Blood Pressure (mmHg) | -0.24 mmHg | Standard Deviation 13.729 |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 4 | Change From Baseline of Systolic and Diastolic Blood Pressure | Week 4 of each treatment cycle - Diastolic Blood Pressure (mmHg) | 3.96 mmHg | Standard Deviation 9.343 |
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 who received at least one injection with study medication and for whom data are available for the respective timepoint. They 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 | -33.50 score on a scale | Standard Deviation 33.1 |
| 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 | 41.56 score on a scale | Standard Deviation 26.649 |
| 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 | -37.55 score on a scale | Standard Deviation 29.414 |
| 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 | -2.49 score on a scale | Standard Deviation 3.997 |
| 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 | -40.59 score on a scale | Standard Deviation 30.511 |
| 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 | -0.20 score on a scale | Standard Deviation 4.158 |
| 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 | -4.22 score on a scale | Standard Deviation 20.426 |
| 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 | -10.38 score on a scale | Standard Deviation 20.596 |
| 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 | -6.84 score on a scale | Standard Deviation 18.238 |
| 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 | 4.84 score on a scale | Standard Deviation 17.932 |
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)
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 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)
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 | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Botulinum Toxin A | Number of Participants With Neutralizing Anti-Drug Antibodies | 0 Participants |
| Placebo | Number of Participants With Neutralizing Anti-Drug Antibodies | 0 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Neutralizing Anti-Drug Antibodies | 0 Participants |
Secondary
Number of Participants With Normal and Abnormal Electrocardiogram
Safety assessments by evaluating Electrocardiogram as per the study schedule
Time frame: Last visit of Treatment Cycle 1 (End of Cycle procedures) conducted upon confirmation of eligibility for retreatment, which was assessed starting 12 weeks post-treatment with 4-weekly evaluations up to a maximum of 48 weeks post treatment.
Population: The population used consists of all subjects who received at least one injection with study medication and who have data available post-baseline and the respective category of baseline electrocardiogram interpretation. Participants were analyzed as treated.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | Number of Participants With Normal and Abnormal Electrocardiogram | Last observation in Cycle 1 - Normal | 79 Participants |
| Botulinum Toxin A | Number of Participants With Normal and Abnormal Electrocardiogram | Last observation in Cycle 1 - Abnormal | 28 Participants |
| Placebo | Number of Participants With Normal and Abnormal Electrocardiogram | Last observation in Cycle 1 - Abnormal | 29 Participants |
| Placebo | Number of Participants With Normal and Abnormal Electrocardiogram | Last observation in Cycle 1 - Normal | 14 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Normal and Abnormal Electrocardiogram | Last observation in Cycle 1 - Normal | 26 Participants |
| Botulinum Toxin A Open Label Extension Arm | Number of Participants With Normal and Abnormal Electrocardiogram | Last observation in Cycle 1 - Abnormal | 6 Participants |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Number of Participants With Normal and Abnormal Electrocardiogram | Last observation in Cycle 1 - Normal | 6 Participants |
| Botulinum Toxin A Open Label Extension Arm - Treatment Cycle 3 | Number of Participants With Normal and Abnormal Electrocardiogram | Last observation in Cycle 1 - Abnormal | 11 Participants |
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs)
Frequency, severity and causal relationship of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) during the entire study period.
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) | 38 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 | 5 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 | 2 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 any Serious 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 Adverse Events of Special Interest (AESI) | 3 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 any Treatment Emergent Adverse Event (TEAE) | 7 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 Serious 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 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 Study Medication Related TEAE | 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 Injection Procedure Related 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 any Adverse Events of Special Interest (AESI) | 1 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 | 1 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) | 50 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 | 2 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 who received at least one injection with 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 | 7 Participants |
| Placebo | Percentage of Responders at Maximum Frown at Week 12 | 0 Participants |
p-value: 0.087Cochran-Mantel-Haenszel
Secondary
Percentage of Responders at Maximum Frown 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 who received at least one injection with study medication and 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 Maximum Frown at Week 16 | 5 Participants |
| Placebo | Percentage of Responders at Maximum Frown at Week 16 | 0 Participants |
p-value: 0.121Cochran-Mantel-Haenszel
Secondary
Percentage of Responders at Maximum Frown 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, Week 8
Population: The population used consists of all randomized subjects who received at least one injection with 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 | Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8 | Week 1 | 66 Participants |
| Botulinum Toxin A | Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8 | Week 2 | 89 Participants |
| Botulinum Toxin A | Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8 | Week 8 | 42 Participants |
| Placebo | Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8 | Week 1 | 1 Participants |
| Placebo | Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8 | Week 2 | 1 Participants |
| Placebo | Percentage of Responders at Maximum Frown at Weeks 1, 2 and 8 | Week 8 | 1 Participants |
Secondary
Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32
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 the respective 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, Week 24, Week 28, Week 32
Population: The population used consists of all randomized subjects who received at least one injection with study medication and for whom data are available for the respective visit. They were analyzed as randomized. In addition, only for Week 20 visit participants who were re-treated before week 20 were counted as non-responders in the analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 | Week 20 | 2 Participants |
| Botulinum Toxin A | Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 | Week 24 | 1 Participants |
| Botulinum Toxin A | Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 | Week 28 | 0 Participants |
| Botulinum Toxin A | Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 | Week 32 | 0 Participants |
| Placebo | Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 | Week 32 | 0 Participants |
| Placebo | Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 | Week 20 | 0 Participants |
| Placebo | Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 | Week 28 | 0 Participants |
| Placebo | Percentage of Responders at Maximum Frown at Weeks 20, 24, 28 and 32 | Week 24 | 0 Participants |
Comparison: Test performed for responders rates at week 20p-value: 0.218Cochran-Mantel-Haenszel
Secondary
Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs
The percentage of subjects with ≥ 2-point 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 raters' 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, Week 4, Week 12, Week 16, Week 20
Population: The population used consists of all randomized subjects who received at least one injection with study medication and for whom data are available for the respective timepoint. Participants were analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 20 | 1 Participants |
| Botulinum Toxin A | Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 2 | 91 Participants |
| Botulinum Toxin A | Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 4 | 88 Participants |
| Botulinum Toxin A | Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 12 | 18 Participants |
| Botulinum Toxin A | Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 16 | 4 Participants |
| Placebo | Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 16 | 0 Participants |
| Placebo | Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 12 | 1 Participants |
| Placebo | Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 2 | 1 Participants |
| Placebo | Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 20 | 0 Participants |
| Placebo | Percentage of Subjects With ≥ 2-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) Based on Independent Raters' Assessment of of Photographs | Week 4 | 1 Participants |
Secondary
Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs
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 raters' assessment of photographs. 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, Week 24, Week 28
Population: The population used consists of all randomized subjects who received at least one injection with study medication and for whom data are available for the respective timepoint. Participants were analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 12 | 41 Participants |
| Botulinum Toxin A | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 20 | 2 Participants |
| Botulinum Toxin A | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 4 | 53 Participants |
| Botulinum Toxin A | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 24 | 2 Participants |
| Botulinum Toxin A | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 16 | 6 Participants |
| Botulinum Toxin A | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 28 | 1 Participants |
| Botulinum Toxin A | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 2 | 45 Participants |
| Placebo | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 28 | 0 Participants |
| Placebo | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 2 | 7 Participants |
| Placebo | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 4 | 8 Participants |
| Placebo | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 12 | 6 Participants |
| Placebo | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 16 | 0 Participants |
| Placebo | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 20 | 0 Participants |
| Placebo | Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photographs | Week 24 | 0 Participants |
Secondary
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
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 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: Week 4 of Treatment Cycles 2, 3 and 4
Population: The population used consists of all randomized subjects who received at least one injection with study medication in the respective treatment cycle and for whom data are available for the respective timepoint. Participants were analyzed as randomized.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Botulinum Toxin A | 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 | Week 4 after 1st Re-treatment | 73 Participants |
| Botulinum Toxin A | 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 | Week 4 after 2nd Re-treatment | 47 Participants |
| Botulinum Toxin A | 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 | Week 4 after 3rd Re-treatment | 44 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: Week 4 of Treatment Cycles 1, 2, 3 and 4
Population: The population used consists of all randomized subjects who received at least one injection with study medication in the respective treatment cycle. 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 - expected | Somewhat 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 - pleased | Definitely agree | 94 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 | 43 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 | 77 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 - expected | Missing | 6 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 | 6 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 | 19 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 | 38 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 | 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 - miraculous | Missing | 6 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 | 35 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 | 53 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 | 36 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 | 30 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 | 35 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 | 6 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 | 68 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 | 38 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 | 22 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 | 26 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 mirror | Missing | 6 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 mirror | Definitely agree | 66 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 mirror | Somewhat agree | 42 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 mirror | Somewhat 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 - look in mirror | Definitely disagree | 21 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 | 6 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 | 82 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 | 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 - pleased | Somewhat disagree | 6 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 | 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 disagree | 37 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 | 6 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 | 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 - pleased | Missing | 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 - expected | Definitely disagree | 40 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 | 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 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 - expected | Missing | 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 - great | Definitely disagree | 39 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 | 6 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 | 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 - great | Definitely agree | 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 - great | Missing | 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 - look in mirror | Definitely disagree | 37 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 mirror | Somewhat disagree | 6 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 mirror | Somewhat agree | 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 mirror | Definitely agree | 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 mirror | Missing | 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 - fantastic | Definitely disagree | 42 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 | 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 | 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 | 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 | Missing | 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 - miraculous | Definitely disagree | 42 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 | 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 - miraculous | 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 - miraculous | Definitely 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 - 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 | Missing | 0 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 | 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 - expected | Definitely 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 4 Week 4 - look in mirror | Missing | 0 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 | 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 4 Week 4 - look in mirror | Definitely agree | 57 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 - look in mirror | Somewhat 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 4 Week 4 - expected | Definitely agree | 76 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 mirror | Somewhat disagree | 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 4 Week 4 - expected | Missing | 0 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 mirror | Definitely 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 - great | 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 4 Week 4 - great | Missing | 0 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 | 27 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 | 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 4 Week 4 - great | Somewhat agree | 27 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 | 14 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 | 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 2 Week 4 - pleased | Somewhat 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 2 Week 4 - pleased | Definitely agree | 113 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 | 2 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 | 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 2 Week 4 - expected | Somewhat 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 2 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 2 Week 4 - expected | Definitely agree | 91 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 | 2 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 | 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 2 Week 4 - great | Somewhat disagree | 27 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 | 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 2 Week 4 - great | Definitely agree | 95 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 | 2 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 mirror | 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 - look in mirror | Somewhat disagree | 39 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 mirror | Somewhat agree | 65 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 mirror | 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 2 Week 4 - look in mirror | Missing | 2 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 | 28 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 | 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 2 Week 4 - fantastic | Somewhat agree | 49 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 | 87 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 | 2 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 | 38 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 | 32 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 | 65 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 | 58 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 | 2 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 | 14 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 | 14 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 | 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 3 Week 4 - pleased | Definitely agree | 106 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 | 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 3 Week 4 - expected | Definitely 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 3 Week 4 - expected | 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 3 Week 4 - expected | Somewhat 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 - expected | Definitely agree | 92 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 | 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 3 Week 4 - great | 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 - great | Somewhat disagree | 27 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 | 32 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 | 96 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 | 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 3 Week 4 - look in mirror | 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 - look in mirror | Somewhat disagree | 32 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 mirror | 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 - look in mirror | Definitely agree | 67 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 mirror | Missing | 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 3 Week 4 - fantastic | 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 - fantastic | Somewhat disagree | 32 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 | 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 - fantastic | Definitely agree | 74 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 | 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 3 Week 4 - miraculous | Definitely disagree | 40 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 | 0 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 | 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 4 Week 4 - miraculous | Definitely agree | 44 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 | 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 | Somewhat agree | 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 3 Week 4 - miraculous | 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 - miraculous | Somewhat disagree | 27 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 | 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 - miraculous | Definitely disagree | 42 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 | 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 - fantastic | Missing | 0 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 | 9 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 | 61 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 | 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 4 Week 4 - fantastic | 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 4 Week 4 - pleased | Definitely agree | 84 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 | 26 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 who received at least one injection with study medication and who had 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 | Investigator's In-clinic Assessment | 95 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 | 113 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 | 3 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 | 9 Participants |
Comparison: Test performed for Investigator's In-clinic Assessmentp-value: <0.001Cochran-Mantel-Haenszel
Comparison: Test performed for Subject's In-clinic Assessmentp-value: <0.001Cochran-Mantel-Haenszel
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 who received at least one injection with study medication and for whom data are available for the respective timepoint. 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 | 8.0 Days |
| Placebo | Time to Onset of Effect in the BoNT/A-DP and Placebo Groups in the First Treatment Cycle | NA Days |