E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to severe Glabellar lines |
|
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 |
|
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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10052609 |
E.1.2 | Term | Glabellar frown lines |
E.1.2 | System Organ Class | 100000004858 |
|
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 objective of the study is to assess short-term efficacy and safety of a single
treatment of BTX-A-HAC NG over placebo for the improvement in the appearance
of glabellar lines and to assess the long term safety and efficacy of BTX-A-HAC NG after repeated injections.
The primary objective will be met by demonstrating the superiority of BTX-A-HAC NG over placebo as measured by the ILA of the appearance of the subject’s glabellar lines at maximum frown on Day 29 of the DB period. |
|
E.2.2 | Secondary objectives of the trial |
• To compare the efficacy of a single treatment of BTX-A-HAC NG to placebo on Day 29 of the DB period as measured by the SSA • To compare the efficacy of a single treatment of BTX-A-HAC NG to placebo at all timepoints of the DB period and to assess repeat-treatments in the OL period as measured by the ILA • To compare the efficacy of a single treatment of BTX-A-HAC NG to placebo at all timepoints of the DB period (except on Day 29) and to assess repeat-treatments in the OL period as measured by the SSA • To compare the efficacy of a single treatment of BTX-A-HAC NG to placebo at all timepoints of the DB period and to assess repeat-treatments in the OL period as measured by the ILA . • To assess the short and long term safety of BTX-A-HAC NG treatment for the improvement in appearance of moderate to severe glabellar lines. • To assess the presence of putative antibodies against BTX-A following single injection with BTX-A-HAC NG or placebo and after repeat-treatments with BTX-A-HAC NG. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All subjects must fulfil all of following criteria to be included in the study:
(1) Provision of written informed consent prior to any study related procedures.
(2) Male or female subjects between 18 and 65 years of age.
(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).
No childbearing 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. |
|
E.4 | Principal exclusion criteria |
Subjects will not be included in the study if the subject:
(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 any dermal fillers in the upper face including the
glabellar lines area within the past 3 years and/or skin abrasions/resurfacing
(whatever the interventional technic used) within the past 5 years, or photo
rejuvenation 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 lifts 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
glabellar 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 IMP, including
medications affecting bleeding disorders (antiplatelet agents and/or
anticoagulants given for treatment or prevention of cardio/cerebro vascular
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).
(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 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 curarelike
non depolarising 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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the proportion of responders at Day 29 DB Cycle 1
as measured by the ILA of glabellar lines at maximum frown. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Key secondary endpoints of DB/OL periods include:
• The proportion of responders at each post-treatment visit to the study centre
as measured by the ILA at maximum frown and at rest
• 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 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 (DB
Cycle 1 only)
• Time to retreatment
• Mean change from Baseline to all post-treatment visits (except Day 57 OL
Cycles 2 to 5) in the Face-Q satisfaction with facial appearance scale, the
Face-Q psychological well-being scale and the FACE-Q aging appearance
appraisal score VAS.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. each post-treatment visit to the study centre
2. each re-treatment visit |
|
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 | Yes |
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 | Yes |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
DOUBLE BLIND, PLACEBO CONTROLLED AND OPEN LABEL PHASE |
|
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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
|
|
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 | |
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 days | 0 |