E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of lateral periorbital wrinkles ("Crow's feet") |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052611 |
E.1.2 | Term | Crow's feet |
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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 |
The primary objective of the trial is to show superiority of NT 201 treatment over placebo for both application schemes and to provide evidence that both application schemes are equally effective in subjects with moderate to severe symmetrical lateral periorbital wrinkles in terms of response. Response is hereby defined as an improvement of at least 1 point for either eye area at week 4 compared to baseline according to the RNKLS assessed by an independent rater.
A hierarchical testing procedure will be applied to show at the first level the superiority of the 3-injection regimen over placebo, at the second level superiority of the 4-injection regimen over placebo and at the third level equivalence of the two different NT 201 application schemes.
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E.2.2 | Secondary objectives of the trial |
Analysis and comparison of: - Treatment response rate compared to baseline for either eye area at week 2, week 12 and 20 according to RNKLS - Treatment response rate compared to baseline for either eye area at week 2, week 4, week 12 and week 20 according to RNKLS - Improvement of appearance of lateral periorbital wrinkles for either eye area compared to baseline at week 2, 4, 12 and 20 by the subject`s global assessment - Time to onset of treatment effect for either eye area assessed by the subject at week 2 and week 4 and fading for either eye area assessed by the subject at week 8 and week 12 between treatment groups and application schemes. As part of the safety evaluation during the trial the incidence of adverse events, hematology, clinical biochemistry and botulinum toxin antibody values, vital signs, physical examinations, concomitant medications and concomitant treatments will be investigated.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Moderate (severity score of 2) to severe (severity score of 3) symmetrical lateral periorbital wrinkles assessed by the investigator according to RNKLS - Symmetrical lateral periorbital wrinkles on both sides of the face at rest and at maximum smile - Man or woman between 18 and 60 years of age (inclusively) - Stable medical condition - Sum score of the evaluated questionnaire on quality of life, skin and cosmetics [FLQA-c] must be below the predefined cut-off value of 0 - Willingness of the subject to participate as documented by written informed consent
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E.4 | Principal exclusion criteria |
- Significant facial asymmetry - Previous facial surgery, e.g. face-lifting - Wrinkles not caused by muscular contraction - Previous treatment with Botulinum toxin of any serotype within the last 6 months - Previous treatment with bio-degradable fillers in the periorbital area within the last 12 months - Any previous insertion of permanent material in the periorbital area (regardless of the time between previous treatment and this study) - Any facial cosmetic procedure (e.g., dermal filling, chemical peeling, photo rejuvenation) in the periorbital area within the last 12 months - Planned concomitant treatment with Botulinum toxin of any serotype in any body region during the study period - Any other planned facial aesthetic procedure during the study period - Inability to substantially reduce lateral periorbital wrinkles by physically spreading them apart - Any infection in the area of the injection sites - Any previous surgery or scars in the periorbital area - Any medical condition that may put the subject at increased risk by exposure to NT 201 or one of the ingredients of the formulation - Bleeding disorders - Regular intake of drugs with anticoagulative effect (e.g., warferin, heparin, cumarines, clopidogrel) within the last 10 days - Regular intake of vitamin E or calcium channel blockers within the last 10 days - Concurrent use of aminoglycoside antibiotics or other agents that might interfere with neuromuscular function or that might interfere with the action of Botulinum toxin A - Diagnosis of Lambert Eaton syndrome/myasthenia gravis, amyotrophic lateral sclerosis or any other significant neuromuscular disease that might interfere with this study - Facial or skin conditions that in the opinion of the investigator could affect safety and/or efficacy results (e.g., acne, scars, psoriasis, allergic dermatitis, photodamage) - History of facial nerve palsy, ptosis, weakness of periorbital muscles etc. - Laxity of the lower lid - If in the opinion of the investigator the subject has unrealistic expectations - Pregnant woman, verified by a positive pregnancy test - Nursing woman or woman of childbearing potential without reliable means of contraception (reliable contraception defined as hormonal contraception or intrauterine contraceptive device or combination of two barrier methods (e.g. condom or diaphragm plus spermicidal cream) or woman planning pregnancy during the course of the trial - If in the opinion of the investigator the subject is unlikely to complete all study visits - Participation in a clinical study within 30 days prior to the screening visit - Previous randomization in this clinical study - Other contraindications which in the investigator’s opinion preclude participation in the study - Evidence of recent alcohol or drug abuse - Employees or direct relatives of an employee of the CRO, the Study Center or Merz Pharmaceuticals |
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E.5 End points |
E.5.1 | Primary end point(s) |
The treatment response rate at week 4 (visit 4). A treatment response is defined as an improvement of at least 1 point on the RNKLS at week 4. (Improvement of 1 point on the RNKLS was previously considered to be clinically significant.) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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 | No |
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.8.3 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 11 |