E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
lateral periorbital wrinkles ("Crow's feet") |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 6.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10040867 |
|
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. |
|
E.2.2 | Secondary objectives of the trial |
Secondary objectives of the trial are the analysis and comparison of:
ユ Treatment response rate compared to baseline for either eye area at week 2, week 12 and 20
(visit 3, 6 and 7) according to RNKLS, assessed by an independent rater using standardized
digital photographs
ユ Treatment response rate compared to baseline for either eye area at week 2, week 4, week
12 and week 20 (visit 3, 4, 6 and 7) according to RNKLS, assessed by the investigators
ユ Improvement of appearance of lateral periorbital wrinkles for either eye area compared to
baseline at week 2, 4, 12 and 20 (visit 3, 4, 6 and 7) by the subject`s global assessment
ユ Time to onset of treatment effect for either eye area assessed by the subject at week 2 and
week 4 (visit 3 and 4) and fading for either eye area assessed by the subject at week 8 and
week 12 (visit 5 and 6) |
|
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1.Moderate (severity score of 2) to severe (severity score of 3)symmetrical lateral periorbital wrinkles assessed by the investigator according to RNKLS
2. Symmetrical lateral periorbital wrinkles on both sides of the face
at rest and at maximum smile
3. Man or woman between 18 and 60 years of age (inclusively)
4. Stable medical condition
5. 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 2
6. Willingness of the subject to participate as documented by written
informed consent |
|
E.4 | Principal exclusion criteria |
1.Significant facial asymmetry3
2. Previous facial surgery, e.g. face-lifting
3. Wrinkles not caused by muscular contractions
4.Previous treatment with Botulinum toxin of any serotype within
the last 6 months
5. Previous treatment with bio-degradable fillers in the periorbital
area within the last 12 months
6. Any previous insertion of permanent material in the periorbital
area (regardless of the time between previous treatment and this
study)
7.Any facial cosmetic procedure (e.g., dermal filling, chemical
peeling, photo rejuvenation) in the periorbital area within the last
12 months
8. Planned concomitant treatment with Botulinum toxin of any
serotype in any body region during the study period
9. Any other planned facial aesthetic procedure during the study period
10. Inability to substantially reduce lateral periorbital wrinkles by
physically spreading them apart
11. Any infection in the area of the injection sites
12. Any previous surgery or scars in the periorbital area
13. Any medical condition that may put the subject at increased risk by exposure to NT 201 or one of the ingredients of the formulation
14. Bleeding disorders
15. Regular intake of drugs with anticoagulative effect (e.g.,
warferin, heparin, cumarines, clopidogrel) within the last 10 days
16. Regular intake of vitamin E or calcium channel blockers within the last 10 days
17. 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
18. Diagnosis of Lambert Eaton syndrome/myasthenia gravis, amyotrophic lateral sclerosis or any other significant neuromuscular disease that might interfere with this study
19. 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)
20. History of facial nerve palsy, ptosis, weakness of periorbital muscles etc.
21. Laxity of the lower lid
22. If in the opinion of the investigator the subject has unrealistic
expectations
23. Pregnant woman, verified by a positive pregnancy test
24. 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
25. If in the opinion of the investigator the subject is unlikely to
complete all study visits.
26. Participation in a clinical study within 30 days prior to the screening visit
27. Previous randomization in this clinical study
28. Other contraindications which in the investigatorメs opinion
preclude participation in the study
29. Evidence of recent alcohol or drug abuse
30. Employees or direct relatives of an employee of the CRO, the
Study Center or Merz Pharmaceuticals |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy parameter is the treatment response rate where treatment response is defined as an improvement of at least 1 point on the RNKLS at week 4 (visit 4) for either eye area
compared to the assessment at baseline assessed by an independent rater using standardized digital photographs. Improvement of 1 point on the RNKLS was previously considered to be clinically
significant |
|
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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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
| |
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
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 years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |