A Randomized, Investigator-Blind, Three-arm, Parallel Assignment, Multi-centre, Comparative Efficacy and Safety Evaluation of Three Tacrolimus 0.1% Topical Ointment Formulations
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 76
- 试验地点
- 9
- 主要终点
- The primary objective is to assess the therapeutic response of two test formulations and a reference formulation of tacrolimus 0.1%.
研究概览
简要总结
Atopic dermatitis (AD) is an inflammatory skin disease with a chronically relapsing course, is characterized by episodes of intense pruritus, lichenification, severely dry skin, and a susceptibility to cutaneous infections.
AD is a common skin disease that occurs in persons of all ages. It has increased in prevalence worldwide two- to threefold over the last 50 years.
For almost half a century, conventional management of AD has been based on the use of emollients to alleviate dry skin, coupled with short courses of topical corticosteroids to treat flares. The short-term efficacy of topical corticosteroids in controlling acute symptoms of AD is well established
Although topical corticosteroids are generally well tolerated, they commonly cause skin atrophy and less frequently cause hypopigmentation, secondary infections, and acne
Tacrolimus ointment preparation is an effective alternative to patients
suffering from AD as it has unique mechanism of action. Tacrolimus, a
macrolide immunomodulator, is believed to control atopic dermatitis by
inhibiting T lymphocyte activation, altering cell surface expression on
antigen-presenting dendritic cells and modulating the release of
inflammatory mediators from skin mast cells and basophils. Both short- and
long-term monotherapy with tacrolimus 0.03 and 0.1% ointment improves
moderate to severe atopic dermatitis in adult and pediatric patients. Topical
tacrolimus ointment is well tolerated, with the majority of adverse events
being localized, transient in nature and of mild or moderate severity.
Tacrolimus ointment provides a promising addition to the currently available
treatments for atopic dermatitis.
The results of the pivotal efficacy studies indicate that tacrolimus is
efficacious in the treatment of acute flares of moderate to severe AD and that the benefit is seen within a few days following commencement of treatment.
In the adult population, the higher concentration (0.1%) showed a better
efficacy than 0.03 %. It also seems that patients treated with the higher concentration heal faster. Twice-daily application is more efficacious than once daily application in the first two weeks. Further, patients with atopic dermatitis most likely tend to treat their disease when it is active and will modify the regimen as the condition heals either deliberately or because of poor compliance
The primary objective is to assess the therapeutic response of two test formulations and a reference formulation of tacrolimus 0.1%.
The secondary objectives are to describe the safety profile of the three ointments and to investigate their systemic absorption at steady state.
研究设计
- 研究类型
- Interventional
- 分配方式
- Other
- 盲法
- Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Male or non-pregnant, non-lactating female of any ethnic group, 18 – 70 years of age (both inclusive) at the time of signing the informed consent.
- •2.Patients having atopic dermatitis according to Hanifin and Rajka diagnostic criteria (Appendix I).
- •3.Patients with a grading of moderate to severe AD (i.e. a score of at least 4.5) as defined by the scoring system of Rajka and Langeland (Appendix II).
- •4.Non-immunocompromised adults who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable.
- •[19] 5.Both male and female patients of child bearing potential must be practicing adequate contraception and female patients of child-bearing potential must not be/likely to be pregnant or lactating and must have a negative serum pregnancy test at screening and negative urine pregnancy test at randomization.
- •6.Patient is capable of understanding the purposes and risks of the trial and has given written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- •7.Patient has not taken and agrees not to take any medication or therapy prohibited by the protocol for the entire study period.
排除标准
- •1.Newly diagnosed patients.
- •2.Patients with very severe atopic dermatitis requiring systemic therapy for AD.
- •3.Clinically infected atopic dermatitis at the baseline visit.
- •4.Any dermatological condition other than atopic dermatitis as scar/wound/tattoo at the application site or in its close vicinity that in the investigators opinion may interfere with the evaluation of the patients atopic dermatitis.
- •5.Patient who have not had a minimum washout phase (prior to randomization) as follows: •5 days: medicated topical agents, systemic antihistamines and sedatives •7 days : intranasal or inhaled corticosteroids employed 1 mg/day •4 weeks: systemic corticosteroids and nonsteroidal immunosuppressants •6 weeks: UV treatments 6.History of allergy or hypersensitivity to tacrolimus or any of the ointment excipients, pimecrolimus, any macrolides such as clindamycin, erythromycin, azithromycin, clarithyromycin etc.
- •7.History or known case of congenital or acquired immunodeficiencies, which in the investigator’s opinion would contraindicate the use of immunosuppressants, including but not limited to human immunodeficiency virus (HIV) infection and cancer.
- •8.Patient with a known case of genetic epidermal barrier defect such as Netherton’s syndrome or generalised erythroderma.
- •Patients with a known case of Cushing’s syndrome.
- •Patients with diagnosed hepatic failure:.
结局指标
主要结局
The primary objective is to assess the therapeutic response of two test formulations and a reference formulation of tacrolimus 0.1%.
时间窗: The primary objective is to assess the therapeutic response of two test formulations and a reference formulation of tacrolimus 0.1%.
次要结局
- The secondary objectives are to describe the safety profile of the three ointments and to investigate their systemic absorption at steady state.(NIL)