E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe Glabellar lines |
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E.1.1.1 | Medical condition in easily understood language |
Patients presenting frown lines in the upper face due to aging not associated with any pathological conditions |
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E.1.1.2 | Therapeutic area | Body processes [G] - Physical Phenomena [G01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052609 |
E.1.2 | Term | Glabellar frown lines |
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 |
The primary study objective is to demonstrate the efficacy of a single treatment of an injectable liquid form of Clostridium botulinum toxin type A haemagglutinin complex (BTX A HAC; hereafter referred to as BTX A HAC Next Generation (BTX A HAC NG)), used for the improvement in the appearance of moderate to severe glabellar lines at maximum frown. The primary objective will be accomplished by demonstrating the superiority of BTX A HAC NG over placebo assessed by the Investigator’s live assessment (ILA) of the appearance of glabellar lines at maximum frown at Day 29.
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E.2.2 | Secondary objectives of the trial |
•To compare the efficacy of a single treatment of BTX A HAC NG to placebo at all timepoints (except Day 29), using the ILA of the appearance of glabellar lines at maximum frown. •To compare the efficacy of a single treatment of BTX A HAC NG to placebo at all timepoints, using the ILA of the appearance of glabellar lines at rest. •To compare the efficacy of a single treatment of BTX A HAC NG to placebo at all timepoints, using the subject’s self assessment (SSA) of the appearance of glabellar lines at maximum frown. •To compare the subject’s level of satisfaction with the appearance of their glabellar lines following treatment with BTX A HAC NG or placebo. •To determine the time to onset of treatment response. •To determine the duration of treatment response. •To compare the safety of a single treatment of BTX A HAC NG to placebo in the treatment of glabellar lines.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(1) Provision of written informed consent prior to any study related procedures. (2) Male or female between 18 and 65 years of age, inclusive. (3) Have moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at baseline (Day 1), as assessed by the ILA using a validated 4 point photographic scale. (4) Have moderate or severe (Grade 2 or 3) vertical glabellar lines at maximum frown at baseline (Day 1), as assessed by the SSA using a validated 4-point categorical scale. (5) Are dissatisfied or very dissatisfied (Grade 2 or 3) with their glabellar lines at baseline (Day 1), as assessed by the subject’s level of satisfaction. (6) Have a negative pregnancy test (for females of childbearing potential only). Nonchildbearing potential is defined as post menopausal for at least 1 year, surgical sterilisation at least 3 months before entering the study, or hysterectomy. (7) Have both the time and the ability to complete the study and comply with study instructions.
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E.4 | Principal exclusion criteria |
(1) Previous treatment with any serotype of BTX. (2) Any prior treatment with permanent fillers in the upper face including the glabellar lines area. (3) Any prior treatment with long lasting dermal fillers in the upper face including the glabella lines area within the past 3 years and/or skin abrasions/resurfacing (whatever the interventional technic used) within the past 5 years, or photorejuvenation or skin/vascular laser intervention within the past 12 months. (4) Any planned facial cosmetic surgery during the study. (5) A history of eyelid blepharoplasty or brow lift within the past 5 years. (6) An inability to substantially reduce glabellar lines by physically spreading them apart or lack of capacity to frown. (7) An active infection or other skin problems in the upper face including the glabella lines area (e.g. acute acne lesions or ulcers). (8) Use of concomitant therapy which, in the Investigator’s opinion, would interfere with the evaluation of the safety or efficacy of the study treatment, including medications affecting bleeding disorders (antiplatelet agents and/or anticoagulants given for treatment or prevention of cardiovasular/cerebrovascular diseases). (9) Pregnant women, nursing mothers, or women who are planning a pregnancy during the study, or believe they may be pregnant at the start of the study. Throughout the course of the study, women of childbearing potential must use a reliable form of contraception (e.g. oral contraceptives for more than 12 consecutive weeks, or spermicide and condoms). (10) A history of drug or alcohol abuse. (11) Treatment with an experimental drug or use of any experimental device within 30 days prior to the start of the study and during the conduct of the study. (12) Known allergy or hypersensitivity to any serotype of BTX or any component of BTX A HAC NG. (13) Clinically diagnosed significant anxiety disorder, or any other significant psychiatric disorder (e.g. depression) that might interfere with the subject’s participation in the study. (14) Use of medications that affect neuromuscular transmission, such as curare like nondepolarising agents, lincosamides, polymyxins, anticholinesterases and aminoglycoside antibiotics, within the past 30 days. (15) A history of facial nerve palsy. (16) Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin. (17) The presence of any other condition (e.g. neuromuscular disorder or other disorder that could interfere with neuromuscular function), laboratory finding or circumstance that, in the judgement of the Investigator, might increase the risk to the subject or decrease the chance of obtaining satisfactory data to achieve the objectives of the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
• The proportion of responders at Day 29 in the ILA of glabellar lines at maximum frown. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• The proportion of responders at each post treatment visit to the study centre (except Day 29) as measured by the ILA at maximum frown. • The proportion of responders on Day 29 who remain responders on Days 113, 148 and 183 as measured by the ILA at maximum frown. • The proportion of responders at each post treatment visit to the study centre as measured by the ILA at rest. • The proportion of subjects with a reduction of two or more grades in the severity of glabellar lines at each post treatment visit to the study centre as measured by the ILA at maximum frown. • The proportion of responders at each post treatment visit to the study centre as measured by the SSA at maximum frown. • The proportion of responders at each post treatment visit to the study centre as measured by the subject’s level of satisfaction with the appearance of their glabellar lines. • The time to onset of treatment response based on the subject’s diary card. • Duration of treatment response based on the ILA and SSA at maximum frown.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Each post-treatment visit to the study centre (except Day 29) 2. Responsders on Day 29 who remain responders on Days 113, 148 and 183 3. At each post-treatment visit. 4. At each post-treatment visit to the study centre as measured by the subject’s self-assessment. |
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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 | 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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | 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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |