E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe upper facial lines (horizontal forehead lines, glabellar frown lines, and lateral canthal lines) |
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E.1.1.1 | Medical condition in easily understood language |
Moderate to severe upper facial lines (horizontal forehead lines, glabellar frown lines, and crows feed |
Falten des oberen Gesichtsbereiches (horizontale Stirnfalten, Zornesfalten und Krähenfüße) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048042 |
E.1.2 | Term | Wrinkles |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052609 |
E.1.2 | Term | Glabellar frown lines |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052611 |
E.1.2 | Term | Crow's feet |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040954 |
E.1.2 | Term | Skin wrinkling |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10040785 |
E.1.2 | Term | Skin and subcutaneous tissue disorders |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy of simultaneous intramuscular injections of NT 201 in subjects with moderate to severe upper facial lines [UFL] in comparison to placebo. |
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E.2.2 | Secondary objectives of the trial |
Efficacy and safety of simultaneous single and repeat-dose intramuscular injections of NT 201 in subjects with moderate to severe UFL. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Outpatients (male or female) 18 years of age or older.
• HFL, GFL, and symmetrical LCL of moderate (score 2) to severe (score 3) intensity at maximum contraction as assessed by the investigator and subject according to the Merz Aesthetics Scales. The rating of the investigator and the subject do not have to coincide as long as they are moderate or severe. |
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E.4 | Principal exclusion criteria |
• Previous treatment with botulinum neurotoxin [BoNT] of any serotype in the face within the last 12 months before injection
• Any facial cosmetic procedure within the last 12 months before baseline injection, such as dermal filling, chemical peeling, photo rejuvenation, mesotherapy, photodynamic therapy, laser treatment, ultrasound treatment, tattooing of eyebrows.
• Previous treatment with any biodegradable filler in the face within the last 12 months before injection.
• Any previous insertion of permanent material in the face including any insertion of treads in the upper face or at cheeks (regardless of the time between previous treatment and this study).
• Any medical condition that may put the subject at increased risk with exposure to NT 201, including myasthenia gravis, Lambert-Eaton-Syndrome, amyotrophic lateral sclerosis, or any other disorder that might interfere with neuromuscular function. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary efficacy endpoints and main efficacy estimands: • Proportion of Glabellar Frown Lines (GFL) responders at day 30 • Proportion of Horizontal Forehead Lines (HFL) responders at day 30 • Proportion of Lateral Canthal Lines (LCL) responders at day 30 • Main estimands for primary efficacy endpoints describe the treatment effects of interest for the three treatment areas. For each main primary estimand, the variable attribute corresponds to the respective primary endpoint.
Primary safety endpoint No primary safety endpoint was defined. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary efficacy endpoints: • Day 30 |
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E.5.2 | Secondary end point(s) |
Key secondary efficacy endpoints and main secondary efficacy estimands: • Proportion of subjects with a score of 0 (no) or 1 (mild) on MAS for GFL at maximum contraction as assessed by the investigator at Day 30 of MP. • Proportion of subjects with a score of 0 (no) or 1 (mild) on MAS for HFL at maximum contraction as assessed by the investigator at Day 30 of MP. • Proportion of subjects with a score of 0 (no) or 1 (mild) on MAS for both left and right LCL at maximum contraction as assessed by the investigator at Day 30 of MP. • Proportion of subjects with a score of 0 (no) or 1 (mild) on MAS for GFL at maximum contraction as assessed by the subject at Day 30 of MP. • Proportion of subjects with a score of 0 (no) or 1 (mild) on MAS for HFL at maximum contraction as assessed by the subject at Day 30 of MP. • Proportion of subjects with a score of 0 (no) or 1 (mild) on MAS for both left and right LCL at maximum contraction as assessed by the subject at Day 30 of MP. • Global Aesthetic Improvement Scale [GAIS] as assessed by the subject at Day 30 of MP.
Further secondary efficacy endpoints: • Proportion of subjects with at least one grade improvement from baseline to Day 30 of MP on MAS for GFL at maximum contraction as assessed by the investigator • Proportion of subjects with at least one grade improvement from baseline to Day 30 of MP on MAS for HFL at maximum contraction as assessed by the investigator • Proportion of subjects with at least one grade improvement from baseline to Day 30 of MP on MAS for both left and right LCL at maximum contraction as assessed by the investigator • GAIS as assessed by the investigator at Day 30 of MP • No estimands are defined for further secondary endpoints.
Secondary safety endpoints • Incidence of related treatment-emergent adverse events (TEAEs) in the MP • Incidence of related TEAEs in the OLEX period
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Key secondary efficacy endpoints: • MAS for GFL at maximum contraction at Day 30 of MP. • MAS for HFL at Day 30 of MP. • MAS for both left and right LCL at maximum contraction at Day 30 of MP. • GAIS at Day 30 of MP.
Further secondary efficacy endpoints: • Improvement from baseline to Day 30 of MP on MAS for GFL • Improvement from baseline to Day 30 of MP on MAS for HFL • Improvement from baseline to Day 30 of MP on MAS for both left and right LCL • GAIS at Day 30 of MP
Secondary safety endpoints • Incidence of related TEAEs in the MP • Incidence of related TEAEs in the OLEX period |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Double-Blind Period followed by an Open-Label Treatment Period |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |