| Study characteristics |
| Methods |
Randomised, double‐blind (first cycle), placebo‐controlled and open‐label Phase (2‐5 cycles) multicentre study, phase III trial |
| Participants |
185 participants
Inclusion criteria
Provision of written informed consent prior to any study‐related procedures Male or female participants between 18 and 65 years of age 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 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 Are dissatisfied or very dissatisfied (Grade 2 or 3) with their glabellar lines at Baseline (Day 1), as assessed by the participant's level of satisfaction 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 Have both the time and the ability to complete the study and comply with study instructions
Exclusion Criteria
Previous treatment with any serotype of BTX Any prior treatment with permanent fillers in the upper face including the glabellar lines area 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 Any planned facial cosmetic surgery during the study A history of eyelid blepharoplasty or brow lifts within the past 5 years An inability to substantially reduce glabellar lines by physically spreading them apart or lack of capacity to frown An active infection or other skin problems in the upper face including the glabellar lines area (e.g. acute acne lesions or ulcers) Use of concomitant therapy, which in the investigator's opinion, would interfere with the evaluation of the safety or efficacy of the investigational medicinal product (IMP), including medications affecting bleeding disorders (antiplatelet agents and/or anticoagulants given for treatment or prevention of cardio/cerebrovascular diseases) 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) 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. Known allergy or hypersensitivity to any component of BTX‐A‐HAC NG Clinically‐diagnosed significant anxiety disorder, or any other significant psychiatric disorder (e.g. depression) that might interfere with the participant's participation in the study Use of medications that affect neuromuscular transmission, such as curare‐like non depolarising agents, lincosamides, polymyxins, anticholinesterases and aminoglycoside antibiotics, within the past 30 days A history of facial nerve palsy Marked facial asymmetry, ptosis, excessive dermatochalasis, deep dermal scarring, or thick sebaceous skin 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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| Interventions |
Intervention
Clostridium Botulinum Toxin Type A (BTX A HAC NG), total treatment volume 0.25 mL will be divided into 5 injections (0.05 mL per injections) injected in 5 pre‐defined sites across the glabellar region. A total of 50 U of BTX‐A‐HAC NG will be injected/cycle.
Comparator
Placebo volume 0.25 mL will be divided into 5 injections (0.05 mL per injections) injected in 5 pre‐defined sites across the glabellar region. Administered in Cycle 1 of the double‐blind phase only. |
| Outcomes |
Primary outcome
Secondary outcomes
The proportion of responders at each post‐treatment visit (except Day 29 Cycle 1) as measured by the ILA at maximum frown. [Time Frame: Days 8, 57 and 85 and then every 28 days until retreatment or up to a maximum of 15 months from treatment (end of study), Cycle 1] The proportion of responders on Day 29 Cycle 1 who remain responders on Days 57, 85 as measured by the ILA at maximum frown. [Time Frame: Days 57 and 85 and then every 28 days until retreatment or up to a maximum of 15 months from treatment (end of study), Cycle 1] The proportion of responders at each post‐treatment visit to the study centre as measured by the ILA at rest. [Time Frame: Days 8, 29, 57 and 85 and then every 28 days until retreatment or up to a maximum of 15 months from treatment (end of study), Cycle 1] The proportion of responders at each post‐treatment visit to the study centre as measured by the Subject's Self‐Assessment (SSA) at maximum frown. [Time Frame: Days 8, 29, 57 and 85 and then every 28 days until retreatment or up to a maximum of 15 months from treatment (end of study), Cycle 1] The proportion of responders at each post‐treatment visit to the study centre as measured by the participant's level of satisfaction with the appearance of their glabellar lines. [Time Frame: Days 8, 29, 57 and 85 and then every 28 days until retreatment or up to a maximum of 15 months from treatment (end of study), Cycle 1] The time to onset of treatment response based on the participant's diary card. [Time Frame: Day 1 to 7, Cycle 1] Mean change from Baseline to all post‐treatment visits in the Face‐Q. [ Time Frame: Days 1, 8, 29, 57 and 85 and then every 28 days until retreatment or up to a maximum of 15 months from treatment (end of study), Cycle 1] The proportion of responders at each post‐treatment visit to the study centre as measured by the ILA at maximum frown. [Time Frame: Days 8, 29, 57 and 85 and then every 28 days until retreatment or up to a maximum of 15 months from treatment (end of study), Cycle 1] The proportion of responders at each post‐treatment visit to the study centre as measured by the ILA at rest. [Time Frame: Days 8, 29, 57 and 85 and then every 28 days until retreatment or up to a maximum of 15 months from treatment (end of study), Cycle 1] The proportion of responders at each post‐treatment visit to the study centre as measured by the SSA at maximum frown. [Time Frame: Days 8, 29, 57 and 85 and then every 28 days until retreatment or up to a maximum of 15 months from treatment (end of study), Cycle 1] The proportion of responders at each post‐treatment visit to the study centre as measured by the participant's level of satisfaction with the appearance of their glabellar lines. [Time Frame: Days 8, 29, 57 and 85 and then every 28 days until retreatment or up to a maximum of 15 months from treatment (end of study), Cycle 1] Time between two consecutive injections. [Time Frame: Day 1 Cycle 2 to 5] Mean change from Baseline to all post‐treatment visits in the Face‐Q. [Time Frame: Day 29 in Cycle 1 and Day 85 in Cycles 2 to 5]
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| Notes |
Sponsor Ipsen
Other study ID Y‐52‐52120‐214
We sent an email on April,28 2019. “The Ipsen company answered:These trials have not been published unfortunately.” on June, 27, 2019. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Quote: "computer‐generated randomization lists that were created by "...page95
Comment: we considered it low risk of bias |
| Allocation concealment (selection bias) |
Low risk |
Quote: "computer‐generated randomization lists that were created by "...page95
Comment: we considered it low risk of bias |
| Blinding of participants and personnel (performance bias)
All outcomes |
Unclear risk |
Quote: No information
Comment: we considered it unclear risk of bias |
| Blinding of outcome assessment (detection bias)
All outcomes |
Unclear risk |
Quote: No information
Comment: we considered it unclear risk of bias |
| Incomplete outcome data (attrition bias)
All outcomes |
Low risk |
Quote:Patient disposition is shown in Figure 1...page 95 and 97
Comment: we considered it low risk of bias |
| Selective reporting (reporting bias) |
Low risk |
All prespecified outcomes were reported
Comment: we considered this low risk of bias |
| Other bias |
Low risk |
no other risk of bias was identified |
