E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Facial Rhytides (Forehead Lines, Glabellar Lines) |
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E.1.1.1 | Medical condition in easily understood language |
Facial Rhytides (Forehead Lines, Glabellar Lines) |
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E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10048043 |
E.1.2 | Term | Wrinkling |
E.1.2 | System Organ Class | 100000004858 |
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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 |
To evaluate the safety and efficacy of repeat BOTOX treatment for forehead lines (FHL), defined as treatment of the frontalis muscle (eyebrow elevator) with simultaneous treatment of the glabellar complex (procerus and corrugator muscles, and eyebrow depressors) |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• male or female, 18 years of age or older • horizontal, symmetrical FHL of moderate to severe rating at maximum eyebrow elevation as assessed by both the subject and the investigator using the FWS at day 1 prior to study treatment; investigator and subject baseline FHL ratings at maximum eyebrow elevation must be identical • GL of moderate to severe rating at maximum frown as assessed by the investigator using the FWS at day 1 prior to study treatment |
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E.4 | Principal exclusion criteria |
• prior exposure to botulinum toxin of any serotype for any reason • any of the following procedures or treatments occurring in the specified period prior to enrollment (day 1) - 3 months: any facial nonablative resurfacing laser or light treatment, microdermabrasion, or superficial peels - 6 months: any facial cosmetic procedure with medium depth or deep depth facial chemical peels (eg, trichloroacetic acid and phenol); periorbital, midfacial, or upper facial skin resurfacing; or permanent make-up in the midfacial (extending from inferior orbital margin to level of the nasal base) or upper facial areas - 12 months: any periorbital, midfacial, or upper facial treatment with nonpermanent soft tissue fillers, or treatment with oral retinoids • prior periorbital surgery, facial lift (full-face or mid-face), thread lift, eyebrow lift, or related procedures (eg, eyelid [blepharoplasty] and/or eyebrow surgery) • prior periorbital, midfacial, or upper facial treatment with permanent soft tissue fillers, synthetic implantation (eg, Gore-Tex®), and/or autologous fat transplantation • marked periocular and eyebrow asymmetry assessed by the investigator at maximum contraction (maximum eyebrow elevation for FHL and maximum frown for GL) or rest • marked dermatochalasis, deep dermal scarring, excessively thick sebaceous skin, or the inability to substantially lessen facial lines even by physically spreading them apart, as determined by the investigator • any eyebrow ptosis or eyelid ptosis at baseline, or excessive forehead and eyebrow skin laxity, as determined by the investigator • eyelid folds that reach the pupil or touch the upper lash line • use of the frontalis muscle to move the upper eyelid, as assessed by the investigator • females who are pregnant, nursing, or planning a pregnancy during the conduct of the study |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measures include • investigator-rated assessment of FHL severity at maximum eyebrow elevation using the FWS • subject-rated assessment of FHL severity at maximum eyebrow elevation using the FWS |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The primary efficacy variables will be evaluated across all study visits, with the primary timepoint being day 30 of Period 1. |
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E.5.2 | Secondary end point(s) |
Secondary efficacy measures include • subject-rated assessment of treatment satisfaction using Facial Line Satisfaction Questionnaire (FLSQ) • subject-rated assessment of facial line appearance using the FLO-11 Questionnaire • investigator-rated assessment of FHL severity at rest using the FWS • subject-rated assessment of FHL severity at rest using the FWS • investigator-rated assessment of GL severity at maximum frown using the FWS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The secondary efficacy variables will be evaluated across all study visits, with the primary timepoint being day 30 of Period 1 (except FLSQ item 5, for which the primary timepoint is day 60 of Period 1). |
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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 | Yes |
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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.5.1 | Number of sites anticipated in the EEA | 2 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Ireland |
United States |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |