A Randomized, Double-Blind, Placebo-controlled, Three-arm, Parallel Assignment, Multi-centre, Therapeutic Equivalence Study of Two Tacrolimus 0.1% Topical Ointment Formulations in Adult Patients with Moderate to Severe Atopic Dermatitis
- Conditions
- moderate to severe atopic dermatitisMedDRA version: 17.0Level: PTClassification code 10012438Term: Dermatitis atopicSystem Organ Class: 10040785 - Skin and subcutaneous tissue disordersTherapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
- Registration Number
- EUCTR2011-006236-23-PL
- Lead Sponsor
- Accord Healthcare Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 650
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 for AD, or when those treatments are not advisable in the opinion of the Investigator.
5.Last application of medicated topical agents, intake of systemic antihistamines, intranasal or inhaled corticosteroids (> 1 mg/day) should be minimum 7 days prior to randomization.
6.Last application of tacrolimus ointment, intake of systemic corticosteroids and nonsteroidal immunosuppressants should be minimum 3 weeks prior to randomization.
7.Both male and female patients of child bearing potential must be practicing adequate contraception and female patients of child-bearing potential must not be pregnant or lactating and must have a negative serum pregnancy test at screening and negative urine pregnancy test at randomization.
8.Patient is capable of understanding the purposes and risks of the trial and has given written informed consent, which includes compliance with the study requirements and restrictions listed in the consent form.
9.Patient has not taken and agrees not to take any medication or therapy prohibited by the protocol for the entire study period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 600
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
1.Newly diagnosed or Treatment naïve patients.
2.Patients with mild (Rajka and Langeland score of < 4.5) or very severe atopic dermatitis that requires systemic therapy.
3.Patients in need of undergoing UV treatments for AD.
4.Clinically infected atopic dermatitis at the baseline visit.
5.Any deermatological condition other than atopic dermatitis as scar/wound/tattoo at the application site or in its close vicinity that in the Investigator's opinion may interfere with the evaluation of the patient's atopic dermatitis
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.
9.Patients with a known case of Cushing’s syndrome.
10. Patients with diagnosed hepatic failure:
Serum bilirubin= 1.5 times ULN
Serum AST/ALT= 2.5 times ULN
11. Abnormal baseline findings considered by the Investigator to indicate conditions that might affect study endpoints.
12.Any form of substance abuse (including drug or alcohol abuse), psychiatric disorder or condition which, in the opinion of the Investigator, may invalidate the communication with the Investigator or adversely affect the study outcome.
13.Positive urine drug scan at screening visit for drugs likely to cause abuse.
14.Last participation in any other clinical study involving investigational medicinal product within 60 days of randomization. However, it is at the sole discretion of the Investigator to enroll eligible patients considering elimination half-life of such study drug of last participation and/or pharmacokinetic profile of such drug molecule of last participation and/or other medical judgement (if any) to justify the subject’s participation.
15.Clinically unstable laboratory test results or any other condition that, in the Investigator’s judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective is to establish the therapeutic equivalence between tacrolimus ointment 0.1%, manufactured by Intas Pharmaceuticals Ltd., India and Protopic® (tacrolimus), 0.1% topical ointment manufactured by Astellas Pharma B.V., The Netherlands and marketed by Astellas Pharma Europe Ltd. and to show superiority over vehicle in the treatment of moderate to severe Atopic Dermatitis in adult population.<br>;Secondary Objective: The secondary objectives are to compare the adverse event (AE) profiles of the two ointments and to investigate their systemic absorption at anticipated Cmax.;Primary end point(s): Change from baseline in Eczema Area and Severity Index (EASI) score Week 6 / End of Treatment (EOT) Visit ;Timepoint(s) of evaluation of this end point: Week 6 / End of Treatment (EOT) Visit
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1.Percentage of patients with = 60% improvement on EASI total score Week 6 / End of Treatment (EOT) Visit.<br>2.Change in grading of AD as defined by the scoring system of Rajka and Langeland from baseline as measured at Week 6 / End of Treatment (EOT) Visit. <br>3.Percentage of body surface area affected (% BSA affected) at Week 6 / End of Treatment (EOT) Visit <br>4.Physician’s Assessment of Individual Signs of Atopic Dermatitis at Week 6 / End of Treatment (EOT) Visit 5.Patient’s Assessment of Pruritus at week 6/ End of Treatment (EOT) Visit ;Timepoint(s) of evaluation of this end point: Week 6 / End of Treatment (EOT) Visit<br>