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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.
The study is a parallel-group, randomized, double blind, placebo-controlled study followed by an open label extension.
An interim Analysis will be performed when all subjects finalized the re-evaluation for retreatment visit at week 16 of the first treatment cycle or completed the double blind phase (whichever occurs earlier).
The first treatment cycle of the study will comprise two treatment groups as follows:
After a screening period of up to14 calendar days, subjects will receive the first treatment (BoNT/A-DP or placebo) and attend for visits at 1, 2 and 4 weeks after treatment and at 4 weekly intervals thereafter for evaluation of efficacy and safety (primary and key secondary efficacy endpoints are evaluated in the first treatment cycle in comparison with placebo).
The first treatment cycle will last at least 12 weeks and will end when the subjects qualify for re-treatment (in accordance with the "eligibility for re-treatment criteria"). After the first treatment cycle is completed, all subjects may enter the open label extension phase and will be dosed with BoNT/A-DP (20 U) for subsequent re-treatments.
Evaluation for re-treatment takes place at the earliest at 12 weeks after the first/previous treatment. Subjects who do not qualify for re-treatment at week 12 will have the option (pending eligibility) of re-treatment at a later visit (at 4 weekly intervals thereafter) until they are eligible for re-treatment or until a total of 48 weeks has elapsed since study start. Subjects will attend for visits at 1 and 4 weeks after any re-treatment and at 4 weekly intervals thereafter. At week 2 and week 8 of each open label cycle a telephone call visit will take place. According to the study schedule (Section 2.1 and Section 2.2), a maximum of 4 treatments per subject (4 treatment cycles) is permitted during the study time frame, with treatments separated by a minimum of 12 weeks.
The number of treatments administered per subject will depend on the subject's qualification for re-treatment; however, the last opportunity for re-treatment is at week 48.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Botulinum toxin A | Experimental | Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. |
|
| Placebo | Placebo Comparator | Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. |
|
| Botulinum toxin A Open Label Extension Arm | Experimental | Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Botulinum Toxin A | Drug | Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area |
|
| Measure | Description | Time Frame |
|---|---|---|
| Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at Week 4 Visit Relative to Baseline, Based on Both the Investigators´ and the Subjects´ In-clinic Assessments. | The primary endpoint is the percentage of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 4 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. Thus, the primary endpoint is a composite endpoint comprising investigator and subject assessments of treatment effectiveness. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| 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
|
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Inclusion Criteria:
Subject had a stable medical condition with no uncontrolled systemic disease.
Exclusion Criteria:
Eligibility Criteria for Retreatment
The following criteria had to be met for retreatment:
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| Name | Affiliation | Role |
|---|---|---|
| Jeffrey Adelglass, Dr. | SKINTASTIC Medical | Principal Investigator |
| Sue Ellen Cox, Dr. | Aesthetic Solutions P.A. | Principal Investigator |
| Michael Gold, Dr. | Tennessee Clinical Research Center | Principal Investigator |
| Joely Kaufman-Janette, Dr. | Skin Research Institute LLC | Principal Investigator |
| Susan Taylor, Dr. | Perelman Center for Advanced Medicine-University of Pennsylvania | Principal Investigator |
| Mark Nestor, Dr. | Center for Clinical and Cosmetic Research | Principal Investigator |
| Daniel Mueller, Dr. | Yuvell (Austria) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tennessee Clinical Research Center | Nashville | Tennessee | 37215 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38470985 | Derived | Cox SE, Kaufman-Janette J, Cohen JL, Gold M, Joseph J, Nestor MS, Rzany B, Taylor S, Zhou J, Cecerle M, Pueraro E, Irvine R, Dayan S. LetibotulinumtoxinA Attenuates the Psychological Burden of Glabellar Lines and Is Associated With High Subject Satisfaction in Phase 3 Clinical Trials. Dermatol Surg. 2024 Jun 1;50(6):535-541. doi: 10.1097/DSS.0000000000004152. Epub 2024 Mar 12. |
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This is not decided yet and will be changed accordingly when the decision has been made
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Of 410 enrolled participants, 355 met inclusion criteria and were randomized to treatment.
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| ID | Title | Description |
|---|---|---|
| FG000 | Botulinum Toxin A | Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area |
| FG001 | Placebo | Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area |
| FG002 | Botulinum Toxin A Open Label Extension Arm | Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Double-Blind Phase |
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| Open-Label Phase |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Botulinum Toxin A | Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | The population used consists of all randomized subjects, regardless of whether they received study medication. Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale (FWS) at baseline or week 4 were assigned as being non-responders. | Posted | Count of Participants | Participants | Week 4 |
Up to 60 weeks post first treatment
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Botulinum Toxin A | Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Acute myocardial infarction | Cardiac disorders | MedDRA (23.1) | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | MedDRA (23.1) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Development - Head of Clinical Operations | Croma Pharma | +432262684680 | clinical.studies@croma.at |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 15, 2019 | Nov 26, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 4, 2020 | Nov 28, 2024 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D019274 | Botulinum Toxins, Type A |
| ID | Term |
|---|---|
| D001905 | Botulinum Toxins |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
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| Placebo | Drug | injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area |
|
|
| Botulinum Toxin A | Drug | Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles |
|
|
| Week 4 |
| 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. | Week 12 |
| Percentage of Responders at Week 16 | Percentage of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 16 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | Week 16 |
| Percentage of Responders at Week 20 | Percentage of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 20 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | Week 20 |
| 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. | Week 4 |
| Responder Rate at Weeks 1, 2 and 8 | The Percentage of responders among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score at maximum frown of 0 or 1 and an improvement ≥ 2 points in FWS score (at maximum frown) during the first treatment cycle visit relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint, at weeks 1, 2 and 8). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | Week 1, Week 2 and Week 8 |
| The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | The percentage of subjects with ≥ 2-point and ≥ 1 reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle visit relative to baseline, based on the independent rater's assessment of photographs (at baseline and visits 2, 4, 12, 16 and 20 weeks after treatment, within the first treatment cycle). The median value of all assessments of the same photography was considered for analysis. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | Week 2, 4, 12, 16 and 20 |
| 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. | From treatment at Day 0 to Week 4 in Treatment Cycle 1 |
| 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." | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | The percentage of subjects with a ≥ 1 point reduction in Facial Wrinkle Scale (FWS) score at rest in the BoNT/A-DP and placebo groups, relative to baseline, during the first treatment cycle, based on the independent rater's assessment of photos. The median value of all assessments of the same photography was considered for analysis. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | Week 2, Week 4, Week 12, Week 16, Week 20 of Treatment Cycle 1 |
| Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at 4 Weeks After Re-treatment Relative to the Rating at the Preceding End-of-Cycle Visit. | The percentage of subjects with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at 4 weeks after re-treatment relative to the rating at the preceding end-of-cycle visit, based on both the investigator's and the subject's in-clinic assessments (composite endpoint). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | The percentage of subjects with ≥ 1-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle at week 1, 2, 4, 8, 12, 16 and 20 relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). For week 16 and 20 subjects who were re-treated before the respective visits were counted as non-responders. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 of Treatment Cycle 1 |
| The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During Each Re-treatment Cycle at Week 4 Relative to Re-treatment-baseline. | The percentage of subjects with ≥ 1-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP during each re-treatment cycle at week 4 relative to re-treatment baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Number of Participants with treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest (AESIs) | Through study completion (60 weeks) |
| 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. | Through study completion (60 weeks) |
| 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 | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Safety assessments by evaluating change from baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase as per the study schedule | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| 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 | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| Change From to Baseline of Bilirubin, Creatinin | Safety assessments by evaluating change from baseline of Bilirubin, Creatinin as per the study schedule | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| Change From Baseline of Erythrocytes | Safety assessments by evaluating change from baseline of Erythrocytes as per the study schedule | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| Change From Baseline of Erythrocytes MCV | Safety assessments by evaluating change from baseline of Erythrocytes MCV as per the study schedule | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| Change From Baseline of Erythrocyte MCHC, Hemoglobin | Safety assessments by evaluating change from baseline of Erythrocyte MCHC, Hemoglobin as per the study schedule | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Safety assessments by evaluating change from baseline of Lymphocytes/leukocytes, Monocytes/leukocytes, Neutrophils/leukocytes, Basophiles/leukocytes, Eosinophils/leukocytes as per the study schedule | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| 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 | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| Change From Baseline of Pulse Rate | Safety assessments by evaluating change from baseline of Pulse rate as per the study schedule | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
| Number of Participants With Normal and Abnormal Electrocardiogram | Safety assessments by evaluating Electrocardiogram as per the study schedule | Week 4 and last visit of Treatment Cycle 1 (End of Cycle procedures), conducted upon confirmation of eligibility for retreatment, assessed starting 12 weeks post-treatment with 4-weekly evaluations up to a max. of 48 weeks post treatment. |
| Withdrawal by Subject |
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| COVID-19 |
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| Early Termination due to Botox Injection while Participating in the Study |
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| NOT COMPLETED |
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| Placebo |
Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area |
| BG002 | Total | Total of all reporting groups |
| Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants |
|
| Facial Wrinkle Scale at Maximum Frown by Investigator and Subject In-clinic Assessment | Facial Wrinkle Scale 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. | Count of Participants | Participants |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Botulinum Toxin A | Botulinum Toxin A will be administered in double blind fashion in cycle 1. 20 Units will be administered (divided in five 0.1 mL i.m injections) into glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area |
| OG001 | Placebo | Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area |
|
|
|
| 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
| The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized. | Posted | Mean | Standard Deviation | score on a scale | Week 4 |
|
|
|
|
| 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. | The population used consists of all randomized subjects, regardless of whether they received study medication. Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale (FWS) at baseline or week 12 were assigned as being non-responders. | Posted | Count of Participants | Participants | Week 12 |
|
|
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| Secondary | Percentage of Responders at Week 16 | Percentage of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 16 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | The population used consists of all randomized subjects for whom data are available for week 16 or who were re-treated before week 16. They were analyzed as randomized and participants who were re-treated before week 16 were counted as non-responders. | Posted | Count of Participants | Participants | Week 16 |
|
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| Secondary | Percentage of Responders at Week 20 | Percentage of subjects among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at week 20 visit (of the first treatment cycle) relative to baseline (responders), based on both the investigators' and the subjects' in-clinic assessments. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | The population used consists of all randomized subjects for whom data are available for week 20 or who were re-treated before week 20. They were analyzed as randomized and participants who were re-treated before week 20 were counted as non-responders. | Posted | Count of Participants | Participants | Week 20 |
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|
| 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. | The population used consists of all randomized subjects with a Facial Wrinkle Scale (FWS) score at rest >=1 at baseline. Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale at week 4 were assigned as being non-responders. | Posted | Count of Participants | Participants | Week 4 |
|
|
|
| Secondary | Responder Rate at Weeks 1, 2 and 8 | The Percentage of responders among BoNT/A-DP and placebo groups with a Facial Wrinkle Scale (FWS) score at maximum frown of 0 or 1 and an improvement ≥ 2 points in FWS score (at maximum frown) during the first treatment cycle visit relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint, at weeks 1, 2 and 8). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | The population used consists of all randomized subjects, regardless of whether they received study medication. Participants were analyzed as randomized. Participants with missing investigator or subject in-clinic assessments with the Facial Wrinkle Scale (FWS) at baseline or at the respective visit were assigned as being non-responders. | Posted | Count of Participants | Participants | Week 1, Week 2 and Week 8 |
|
|
|
| Secondary | The Percentage of Subjects With ≥ 2-point and ≥ 1 Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) | The percentage of subjects with ≥ 2-point and ≥ 1 reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle visit relative to baseline, based on the independent rater's assessment of photographs (at baseline and visits 2, 4, 12, 16 and 20 weeks after treatment, within the first treatment cycle). The median value of all assessments of the same photography was considered for analysis. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized. | Posted | Count of Participants | Participants | Week 2, 4, 12, 16 and 20 |
|
|
|
| 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. | The population used consists of all randomized subjects. Participants were analyzed as randomized. | Posted | Median | Inter-Quartile Range | Days | From treatment at Day 0 to Week 4 in Treatment Cycle 1 |
|
|
|
| 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." | The population used consists of all randomized subjects who were treated in the respective study cycle and treatment group. Participants were analyzed as randomized. | Posted | Count of Participants | Participants | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
|
|
|
| Secondary | The Percentage of Subjects With a ≥ 1 Point Reduction in Facial Wrinkle Scale (FWS) Score at Rest Based on the Independent Rater's Assessment of Photos. | The percentage of subjects with a ≥ 1 point reduction in Facial Wrinkle Scale (FWS) score at rest in the BoNT/A-DP and placebo groups, relative to baseline, during the first treatment cycle, based on the independent rater's assessment of photos. The median value of all assessments of the same photography was considered for analysis. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized. | Posted | Count of Participants | Participants | Week 2, Week 4, Week 12, Week 16, Week 20 of Treatment Cycle 1 |
|
|
|
| Secondary | Facial Wrinkle Scale (FWS) Score of 0 or 1 and an Improvement of ≥ 2 Points in FWS Score (at Maximum Frown) at 4 Weeks After Re-treatment Relative to the Rating at the Preceding End-of-Cycle Visit. | The percentage of subjects with a Facial Wrinkle Scale (FWS) score of 0 or 1 and an improvement of ≥ 2 points in FWS score (at maximum frown) at 4 weeks after re-treatment relative to the rating at the preceding end-of-cycle visit, based on both the investigator's and the subject's in-clinic assessments (composite endpoint). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized. | Posted | Count of Participants | Participants | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
|
|
|
| Secondary | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During the First Treatment Cycle at Week 1, 2, 4, 8, 12, 16 and 20 Relative to Baseline | The percentage of subjects with ≥ 1-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP and placebo groups during the first treatment cycle at week 1, 2, 4, 8, 12, 16 and 20 relative to baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). For week 16 and 20 subjects who were re-treated before the respective visits were counted as non-responders. FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized. | Posted | Count of Participants | Participants | Week 1, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20 of Treatment Cycle 1 |
|
|
|
| Secondary | The Percentage of Subjects With ≥ 1-point Reduction in Facial Wrinkle Scale (FWS) Score (at Maximum Frown) During Each Re-treatment Cycle at Week 4 Relative to Re-treatment-baseline. | The percentage of subjects with ≥ 1-point reduction in Facial Wrinkle Scale (FWS) score (at maximum frown) in the BoNT/A-DP during each re-treatment cycle at week 4 relative to re-treatment baseline, based on both the investigators' and the subjects' in-clinic assessments (composite endpoint). FWS scores are a four-point rating scale as follows: 0 = no facial wrinkles; 1 = mild facial wrinkles; 2 = moderate facial wrinkles; and 3 = severe facial wrinkles. | The population used consists of all randomized subjects for whom data are available for the respective timepoint. Participants were analyzed as randomized. | Posted | Count of Participants | Participants | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
|
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|
| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious AEs (SAEs) and AEs of Special Interest (AESIs) | Number of Participants with treatment-emergent adverse events (TEAEs), serious AEs (SAEs) and AEs of special interest (AESIs) | The population used consists of all subjects who received at least one injection with study medication. Participants were analyzed as treated. | Posted | Count of Participants | Participants | Through study completion (60 weeks) |
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|
|
| 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. | 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. | Posted | Count of Participants | Participants | Through study completion (60 weeks) |
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| 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 | 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. | Posted | Mean | Standard Deviation | x10^9 cells/L | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
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|
| Secondary | Change From Baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase | Safety assessments by evaluating change from baseline of Alanine Aminotransferase, Alkaline Phosphatase , Aspartate Aminotransferase, Gamma Glutamyl Transpeptidase as per the study schedule | 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. | Posted | Mean | Standard Deviation | U/L | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
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|
|
| 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 | 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. | Posted | Mean | Standard Deviation | mmol/L | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
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|
|
| Secondary | Change From to Baseline of Bilirubin, Creatinin | Safety assessments by evaluating change from baseline of Bilirubin, Creatinin as per the study schedule | 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. | Posted | Mean | Standard Deviation | μmol/L | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
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|
|
| Secondary | Change From Baseline of Erythrocytes | Safety assessments by evaluating change from baseline of Erythrocytes as per the study schedule | 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. | Posted | Mean | Standard Deviation | x10^12 cells/L | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
|
|
|
| Secondary | Change From Baseline of Erythrocytes MCV | Safety assessments by evaluating change from baseline of Erythrocytes MCV as per the study schedule | 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. | Posted | Mean | Standard Deviation | fL | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
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|
| Secondary | Change From Baseline of Erythrocyte MCHC, Hemoglobin | Safety assessments by evaluating change from baseline of Erythrocyte MCHC, Hemoglobin as per the study schedule | 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. | Posted | Mean | Standard Deviation | g/dL | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
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| Secondary | Change From Baseline of Lymphocytes/Leukocytes, Monocytes/Leukocytes, Neutrophils/Leukocytes, Basophiles/Leukocytes, Eosinophils/Leukocytes | Safety assessments by evaluating change from baseline of Lymphocytes/leukocytes, Monocytes/leukocytes, Neutrophils/leukocytes, Basophiles/leukocytes, Eosinophils/leukocytes as per the study schedule | 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. | Posted | Mean | Standard Deviation | % of leukocytes | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
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|
| 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 | 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. | Posted | Mean | Standard Deviation | mmHg | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
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|
|
| Secondary | Change From Baseline of Pulse Rate | Safety assessments by evaluating change from baseline of Pulse rate as per the study schedule | 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. | Posted | Mean | Standard Deviation | bpm | Week4 Cycle1(on average 4 Weeks from Baseline, up to Week 7), Week4 Cycle2 (on average 20 Weeks from Baseline, up to Week 52), Week4 Cycle3 (on average 37 Weeks from Baseline, up to Week 53), Week4 Cycle4 (on average 46 Weeks from Baseline, up to Week 56) |
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| Secondary | Number of Participants With Normal and Abnormal Electrocardiogram | Safety assessments by evaluating Electrocardiogram as per the study schedule | The population used consists of all subjects who received at least one injection with study medication and who have data available for the respective visit and category of baseline electrocardiogram interpretation. Participants were analyzed as treated. | Posted | Count of Participants | Participants | Week 4 and last visit of Treatment Cycle 1 (End of Cycle procedures), conducted upon confirmation of eligibility for retreatment, assessed starting 12 weeks post-treatment with 4-weekly evaluations up to a max. of 48 weeks post treatment. |
|
|
|
| 0 |
| 266 |
| 1 |
| 266 |
| 12 |
| 266 |
| EG001 | Placebo | Placebo will be administered in double blind fashion in cycle 1 divided in five 0.1 mL injections into the glabellar area. Placebo: injection, sodium chloride 0.9 % divided in five 0.1 mL i.m injections into the glabellar area | 0 | 89 | 1 | 89 | 6 | 89 |
| EG002 | Botulinum Toxin A Open Label Extension Arm | Open Label Extension Arm where all Subjects from Arm 1 and 2 can receive Experimental Treatment in up to 3 treatment cycles. 20 Units will be administered (divided in five 0.1 mL i.m. injections) into the glabellar area. Botulinum Toxin A: Injection, 20 Units divided in five 0.1 mL i.m injections into the glabellar area in up to 3 treatment cycles | 0 | 323 | 4 | 323 | 14 | 323 |
| Goitre | Endocrine disorders | MedDRA (23.1) | Non-systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA (23.1) | Non-systematic Assessment |
|
| Cholelithiasis | Hepatobiliary disorders | MedDRA (23.1) | Non-systematic Assessment |
|
| Foot deformity | Musculoskeletal and connective tissue disorders | MedDRA (23.1) | Non-systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA (23.1) | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (23.1) | Non-systematic Assessment |
|
| Tooth fracture | Injury, poisoning and procedural complications | MedDRA (23.1) | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA (23.1) | Non-systematic Assessment |
|
Not provided
Not provided
| D006867 |
| Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
| Moderate facial wrinkles |
|
| Severe facial wrinkles |
|
| Modified Skindex-16 (GL-QoL) Overall score - Change from Baseline at Week 4 |
|
| FACE-Q Appraisal of Lines Between Eyebrows - Change from Baseline at Week 4 |
|
| Age Appraisal VAS - Change from Baseline at Week 4 |
|
Test performed for Modified Skindex-16 (GL-QoL) Social Functioning domain - Change from Baseline at Week 4 |
| Wilcoxon (Mann-Whitney) |
| <0.001 |
The statistical significance is set to 0.025. This is the third test in a hierarchical testing sequence. Statistical significance will only be assessed if the previous two tests show statistical significance at the alpha level of 0.025. |
| Superiority |
| Test performed for Modified Skindex-16 (GL-QoL) Overall score - Change from Baseline at Week 4. | Wilcoxon (Mann-Whitney) | <0.001 | The statistical significance is set to 0.025. This is the forth test in a hierarchical testing sequence. Statistical significance will only be assessed if the previous three tests show statistical significance at the 1-sided alpha level of 0.025. | Superiority |
| Test performed for FACE-Q Appraisal of Lines Between Eyebrows - Change from Baseline at Week 4 | Wilcoxon (Mann-Whitney) | <0.001 | The statistical significance is set to 0.025. This is the fifth test in a hierarchical testing sequence. Statistical significance will only be assessed if the previous four tests show statistical significance at the 1-sided alpha level of 0.025. | Superiority |
| Test performed for FACE-Q Age Appraisal VAS score | Wilcoxon (Mann-Whitney) | <0.001 | The statistical significance is set to 0.025. This is the sixth test in a hierarchical testing sequence. Statistical significance will only be assessed if the previous five tests show statistical significance at the 1-sided alpha level of 0.025. | Superiority |
| Subject's In-clinic Assessment |
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|
| Week 8 |
|
| ≥ 2-point reduction - Week 4 |
|
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| ≥ 2-point reduction - Week 12 |
|
|
| ≥ 2-point reduction - Week 16 |
|
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| ≥ 2-point reduction - Week 20 |
|
|
| ≥ 1-point reduction - Week 2 |
|
|
| ≥ 1-point reduction - Week 4 |
|
|
| ≥ 1-point reduction - Week 12 |
|
|
| ≥ 1-point reduction - Week 16 |
|
|
| ≥ 1-point reduction - Week 20 |
|
|
| Somewhat disagree |
|
| Somewhat agree |
|
| Definitely agree |
|
| Missing |
|
| Cycle 1 Week 4 - expected |
|
|
| Cycle 1 Week 4 - great |
|
|
| Cycle 1 Week 4 - look in the mirror |
|
|
| Cycle 1 Week 4 - fantastic |
|
|
| Cycle 1 Week 4 - miraculous |
|
|
| Cycle 2 Week 4 - pleased |
|
|
| Cycle 2 Week 4 - expected |
|
|
| Cycle 2 Week 4 - great |
|
|
| Cycle 2 Week 4 - look in the mirror |
|
|
| Cycle 2 Week 4 - fantastic |
|
|
| Cycle 2 Week 4 - miraculous |
|
|
| Cycle 3 Week 4 - pleased |
|
|
| Cycle 3 Week 4 - expected |
|
|
| Cycle 3 Week 4 - great |
|
|
| Cycle 3 Week 4 - look in the mirror |
|
|
| Cycle 3 Week 4 - fantastic |
|
|
| Cycle 3 Week 4 - miraculous |
|
|
| Cycle 4 Week 4 - pleased |
|
|
| Cycle 4 Week 4 - expected |
|
|
| Cycle 4 Week 4 - great |
|
|
| Cycle 4 Week 4 - look in the mirror |
|
|
| Cycle 4 Week 4 - fantastic |
|
|
| Cycle 4 Week 4 - miraculous |
|
|
| Week 4 |
|
|
| Week 12 |
|
|
| Week 16 |
|
|
| Week 20 |
|
|
|
| Week 4 after 3rd Re-treatment |
|
|
| Week 2 |
|
|
| Week 4 |
|
|
| Week 8 |
|
|
| Week 12 |
|
|
| Week 16 |
|
|
| Week 20 |
|
|
|
| Week 4 after 3rd Re-treatment |
|
|
|
| Subjects with any Injection Procedure Related TEAE |
|
| Subjects with any Severe TEAE |
|
| Subjects with severe study drug related TEAE |
|
| Subjects with severe injection procedure related TEAE |
|
| Subjects with any Serious TEAE |
|
| Subjects with any Adverse Events of Special Interest (AESI) |
|
| Subjects with any TEAE leading to discontinuation |
|
| Baseline - ADA Confirmation Assay - Confirmed |
|
|
| End of Study - ADA Screening Assay - Reactive |
|
|
| End of Study - ADA Confirmation Assay - Confirmed |
|
|
| Week 4 of cycle 1 - Eosinophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 1 - Leukocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 1 - Lymphocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 1 - Monocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 1 - Neutrophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 1 - Platelets (x10^9 cells/L) |
|
|
| Week 4 of cycle 2 - Basophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 2 - Eosinophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 2 - Leukocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 2 - Lymphocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 2 - Monocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 2 - Neutrophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 2 - Platelets (x10^9 cells/L) |
|
|
| Week 4 of cycle 3 - Basophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 3 - Eosinophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 3 - Leukocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 3 - Lymphocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 3 - Monocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 3 - Neutrophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 3 - Platelets (x10^9 cells/L) |
|
|
| Week 4 of cycle 4 - Basophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 4 - Eosinophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 4 - Leukocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 4 - Lymphocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 4 - Monocytes (x10^9 cells/L) |
|
|
| Week 4 of cycle 4 - Neutrophils (x10^9 cells/L) |
|
|
| Week 4 of cycle 4 - Platelets (x10^9 cells/L) |
|
|
| Week 4 of cycle 1 - Alkaline phosphatase (U/L) |
|
|
| Week 4 of cycle 1 - Aspartate Aminotransferase (U/L) |
|
|
| Week 4 of cycle 1 - Gamma Glutamyl Transpeptidase (U/L) |
|
|
| Week 4 of cycle 2 - Alanine Aminotransferase (U/L) |
|
|
| Week 4 of cycle 2 - Alkaline phosphatase (U/L) |
|
|
| Week 4 of cycle 2 - Aspartate Aminotransferase (U/L) |
|
|
| Week 4 of cycle 2 - Gamma Glutamyl Transpeptidase (U/L) |
|
|
| Week 4 of cycle 3 - Alanine Aminotransferase (U/L) |
|
|
| Week 4 of cycle 3 - Alkaline phosphatase (U/L) |
|
|
| Week 4 of cycle 3 - Aspartate Aminotransferase (U/L) |
|
|
| Week 4 of cycle 3 - Gamma Glutamyl Transpeptidase (U/L) |
|
|
| Week 4 of cycle 4 - Alanine Aminotransferase (U/L) |
|
|
| Week 4 of cycle 4 - Alkaline phosphatase (U/L) |
|
|
| Week 4 of cycle 4 - Aspartate Aminotransferase (U/L) |
|
|
| Week 4 of cycle 4 - Gamma Glutamyl Transpeptidase (U/L) |
|
|
| Week 4 of of cycle 1 - Glucose (mmol/L) |
|
|
| Week 4 of of cycle 1 - Potassium (mmol/L) |
|
|
| Week 4 of of cycle 1 - Sodium (mmol/L) |
|
|
| Week 4 of of cycle 1 - Urea nitrogen (mmol/L) |
|
|
| Week 4 of cycle 2 - Cholesterol (mmol/L) |
|
|
| Week 4 of of cycle 2 - Glucose (mmol/L) |
|
|
| Week 4 of of cycle 2 - Potassium (mmol/L) |
|
|
| Week 4 of of cycle 2 - Sodium (mmol/L) |
|
|
| Week 4 of of cycle 2 - Urea nitrogen (mmol/L) |
|
|
| Week 4 of cycle 3 - Cholesterol (mmol/L) |
|
|
| Week 4 of of cycle 3 - Glucose (mmol/L) |
|
|
| Week 4 of of cycle 3 - Potassium (mmol/L) |
|
|
| Week 4 of of cycle 3 - Sodium (mmol/L) |
|
|
| Week 4 of of cycle 3 - Urea nitrogen (mmol/L) |
|
|
| Week 4 of of cycle 4 - Cholesterol (mmol/L) |
|
|
| Week 4 of of cycle 4 - Glucose (mmol/L) |
|
|
| Week 4 of of cycle 4 - Potassium (mmol/L) |
|
|
| Week 4 of of cycle 4 - Sodium (mmol/L) |
|
|
| Week 4 of of cycle 4 - Urea nitrogen (mmol/L) |
|
|
| Week 4 of cycle 1 - Creatinine (μmol/L) |
|
|
| Week 4 of cycle 2 - Bilirubin (μmol/L) |
|
|
| Week 4 of cycle 2 - Creatinine (μmol/L) |
|
|
| Week 4 of cycle 3 - Bilirubin (μmol/L) |
|
|
| Week 4 of cycle 3 - Creatinine (μmol/L) |
|
|
| Week 4 of cycle 4 - Bilirubin (μmol/L) |
|
|
| Week 4 of cycle 4 - Creatinine (μmol/L) |
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| Cycle 2 |
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| Cycle 3 |
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| Cycle 4 |
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| Cycle 2 |
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| Cycle 3 |
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| Cycle 4 |
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| Week 4 of cycle 1 - Hemoglobin (g/dL) |
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| Week 4 of cycle 2 - Erythrocyte MCHC (g/dL) |
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| Week 4 of cycle 2 - Hemoglobin (g/dL) |
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| Week 4 of cycle 3 - Erythrocyte MCHC (g/dL) |
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| Week 4 of cycle 3 - Hemoglobin (g/dL) |
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| Week 4 of cycle 4 - Erythrocyte MCHC (g/dL) |
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| Week 4 of cycle 4 - Hemoglobin (g/dL) |
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| Week 4 of cycle 1 - Eosinophils/leukocytes (%) |
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| Week 4 of cycle 1 - Lymphocytes/leukocytes (%) |
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| Week 4 of cycle 1 - Monocytes/leukocytes (%) |
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| Week 4 of cycle 1 - Neutrophils/leukocytes (%) |
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| Week 4 of cycle 2 - Basophiles/leukocytes (%) |
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| Week 4 of cycle 2 - Eosinophils/leukocytes (%) |
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| Week 4 of cycle 2 - Lymphocytes/leukocytes (%) |
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| Week 4 of cycle 2 - Monocytes/leukocytes (%) |
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| Week 4 of cycle 2 - Neutrophils/leukocytes (%) |
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| Week 4 of cycle 3 - Basophiles/leukocytes (%) |
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|
| Week 4 of cycle 3 - Eosinophils/leukocytes (%) |
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|
| Week 4 of cycle 3 - Lymphocytes/leukocytes (%) |
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|
| Week 4 of cycle 3 - Monocytes/leukocytes (%) |
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|
| Week 4 of cycle 3 - Neutrophils/leukocytes (%) |
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|
| Week 4 of cycle 4 - Basophiles/leukocytes (%) |
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|
| Week 4 of cycle 4 - Eosinophils/leukocytes (%) |
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|
| Week 4 of cycle 4 - Lymphocytes/leukocytes (%) |
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|
| Week 4 of cycle 4 - Monocytes/leukocytes (%) |
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|
| Week 4 of cycle 4 - Neutrophils/leukocytes (%) |
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|
| Week 4 of cycle 1 - Diastolic Blood Pressure (mmHg) |
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| Week 4 of cycle 2 - Systolic Blood Pressure (mmHg) |
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| Week 4 of cycle 2 - Diastolic Blood Pressure (mmHg) |
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| Week 4 of cycle 3 - Systolic Blood Pressure (mmHg) |
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| Week 4 of cycle 3 - Diastolic Blood Pressure (mmHg) |
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| Week 4 of cycle 4 - Systolic Blood Pressure (mmHg) |
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| Week 4 of cycle 4 - Diastolic Blood Pressure (mmHg) |
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| Cycle 2 |
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| Cycle 3 |
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| Cycle 4 |
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| Cycle 1 End of Cycle Visit - Electrocardiogram Interpretation |
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| Abnormal |
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