A randomized, double-blind, Placebo-controlled, three arms, parallel-group, multiple-site bioequivalence study with clinical endpoints
Scientific Title of Study
A Randomized, Double-Blind, Placebo-Controlled,three arm, Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic Equivalence and Safety of Tacrolimus Ointment, 0.1% (EncubeEthicals Private Limited)with Protopic® (tacrolimus) ointment, 0.1% (AstellasPharma US, Inc.) in the Treatment of Moderate to SevereAtopic Dermatitis.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ARL/CT/18/002 (Version 2, Amendment 1, Dated 06 Oct 2018
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Ajaykumar Malle
Designation
Medical Monitor
Affiliation
Accutest Research Laboratories (I) Pvt.Ltd
Address
A-77 Khairne MIDC TTC Industrial Area
Khairne Navi Mumbai
Thane MAHARASHTRA 400709 India
Phone
02227780718
Fax
02227780720
Email
ajay.malle@accutestglobal.com
Details of Contact Person Public Query
Name
Sushant Dhabekar
Designation
Clinical Project Manager
Affiliation
Accutest Research Laboratories (I) Pvt.Ltd.
Address
Opp. The Grand Bhagwati
S.G. Highway
Bodakdev Ahmedabad
Ahmadabad GUJARAT 380 059 India
Phone
07940231600
Fax
Email
sushant.dhabekar@accutestglobal.com
Source of Monetary or Material Support
Encube Ethicals Private Limited Unit No. 24, Steelmade Industrial Estate, Marol Village,
Andheri (East), Mumbai-400059 Maharashtra
Primary Sponsor
Name
Encube Ethicals Private Ltd
Address
Unit 24, Steelmade Industrial Estate,
Marol Village Andheri (E) Mumbai- 400 059 India.
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
India
Sites of Study
No of Sites = 20
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Madhu Shah
Bodyline Hospital
Department of
Dermatology, 2nd
Floor, Annapurna
Hall, Near Dev
status, New Vikas
Gruh Road, Paldi,
Ahmedabad- 380004
Ahmedabad, GUJARAT Ahmadabad GUJARAT
9824076703 7923969452 drmshah61@gmail.com
Dr Shatrughan Sahay
Ajanta Research Center, Ajanata Hospital and IVF Center,
Dept of Dermatology,
3rd floor, Nr. Bharat
Petrol Pump, Nr.
Lakhudi Talav,
Stadium Road,
Navarangpura, -380014 Ahmadabad GUJARAT
07961908000 07961908099 nagpalsmita@gmail.com
Dr Rameshchand Jain
Vijay Vallabh Hospital
Department of Dermatology, Unit of Tirupati Life care, Plot No. 423, Tirupati Nagar, Phase 1, Boling, Virar (West) - 401303, Maharashtra, India. Thane MAHARASHTRA
07030333226 07030333227 drrameshjain@gmail.com
Details of Ethics Committee
No of Ethics Committees= 20
Name of Committee
Approval Status
Bodyline hospital Ethics Committee
Submittted/Under Review
Grand Govt Medical college and sir JJ group of Hospitals- Institutional Ethics Committee
Submittted/Under Review
Hi Tech Ethics Committee
Submittted/Under Review
Instititional Ethics Committee Om Surgical Centre and Maternity Home
Submittted/Under Review
Institutional Ethical Committee, Apple Saraswati Multispeciality Hospital
Submittted/Under Review
Institutional Ethics Committee Ajanta Hospital & IVF Centre
Submittted/Under Review
Institutional Ethics Committee GMERS Medical college & Civil Hospital Sola
Submittted/Under Review
Institutional Ethics Committee of Ishwar Institute of Health Care
Submittted/Under Review
Institutional Ethics Committee- Human Research (IEC-HR)
Submittted/Under Review
Kanoria Ethics Committee
Submittted/Under Review
KRM Hospital Ethics Committee
Submittted/Under Review
Lotus Ethics Committee
Submittted/Under Review
LPR Ethics Committee
Approved
Medistar Hospital Ethics Committee
Submittted/Under Review
MGM Ethics Committee for Research on Human Subjects
Approved
Padmashree Dr. D Y Patil Medical College, Hospital & Research Centre-Institutional Ethics Committee
Manufactured by: AstellasPharma US, Inc. Application:The study product will be applied in a thin layer to the affected areas twice daily (morning and evening).Â
Intervention
Tacrolimus Onitment, 0.1%Â
Manufacture by: Encube Ethicals Private Limited Application:The study product will be applied in a thin layer to the affected areas twice daily (morning and evening).Â
Comparator Agent
Vehicle of Tacrolimus Onitment, 0.1%Â
Manufactured by: Encube Ethicals Private Limited. Application:The study product will be applied in a thin layer to the affected areas twice daily (morning and evening).
Inclusion Criteria
Age From
18.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Non Immunocompromised Male or non-pregnant, non-lactating female, 18 years and older at the time of signing the informed consent.
2. Subjects having confirmed diagnosis of atopic dermatitis for at least 3 months.
3. Subject with clinical diagnosis of moderate to severeatopic dermatitis that has failed to respond adequately to other topical prescription treatments for atopic dermatitis, or for whom those treatments are not advisable per Investigator.
4. Subject having an Investigator’s Global Assessments (IGA) of disease severity of at least moderate [a score of 3 (moderate) or 4 (severe)] AND have a minimum SCORAD score of disease severity is >15.
5. Subject having an affected area of AD involvement of at least 20% Body Surface Area (BSA) at baseline, as defined by the Hanifin and Rajka criteria.
6. Subject 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. Both male and female subjects of child bearing potential must be practicing adequate contraception (for example total abstinence, intrauterine device, a double-barrier method, oral, transdermal, injected, or implanted non-hormonal or hormonal contraceptive) throughout the studyand female subjects of childbearing 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.
8. Subject agrees to compliance with the protocol and adheres to the protocol requirements for the entire study period.
ExclusionCriteria
Details
1. Subjects with diagnosis of atopic dermatitis for less than 3 months.
2. Reports active cutaneous bacterial or viral infection in any treatment area at baseline (e.g.,clinically infected atopic dermatitis).
3. Sunburn, extensive scarring, or pigmented lesion(s) in any treatment area at baseline, which would interfere with evaluations.
4. History of confounding skin conditions, e.g., psoriasis, rosacea, erythroderma, orichthyosis
5. Females who are pregnant, lactating or likely to become pregnant during the study.
6. History or presence of Netherton’s Syndrome, immunological deficiencies or diseases, HIV, diabetes, malignancy, serious active or recurrent infection, clinically significant severe renal insufficiency or severe hepatic disorders.
7. Use within one month prior to baseline of 1) oral or intravenous corticosteroids, 2) UVA/UVB therapy, 3) PUVA (psoralen plus ultraviolet A) therapy, 4) tanning booths, 5) nonprescription UV light sources, 6) immunomodulators or immunosuppressive therapies, 7) interferon, 8) cytotoxic drugs, 9) Tacrolimus, or 10) Pimecrolimus.
8. Use within 14 days of baseline of: 1) systemic antibiotics, 2) Calcipotriene or other Vitamin D preparations, or 3) retinoids.
9. Use within 7 days prior to baseline of: 1) antihistamines, 2) topical antibiotics, 3) topical corticosteroids or 4) other topical drug products.
10. Use within 24 hours prior to baseline of any topical product (e.g., sunscreens, lotions, creams, emollient, moisturizers) in the areas to be treated.
11. Known allergy or hypersensitivity to Tacrolimus or any other component of the test product or RLD.
12. Not willing to minimize or avoid natural and artificial sunlight exposure during treatment.
13. Subjects with clinically significant unstable medical disorders, life-threatening disease, or current malignancies.
14. Demonstrates a positive test result for Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody.
15. Reports simultaneous participation in any other drug trial or participation in any other trial involving investigational medicinal product within 30 days of randomization. However, subjects can be enrolled considering elimination half-life of study drug of last participation and/or pharmacokinetic profile of such drug molecule of last participation and/or other medical judgment (if any) to justify the subject’s participation based on investigator opinion and/or sponsor medical monitor.
16. Any other condition, that in the investigator’s judgment, might compromise subject safety or affect study results
17. Abnormal baseline findings considered by the investigator to indicate conditions that might affect study endpoints and/or might increase the risk to the subject or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
18. Employees of the Investigator or research centre or their immediate family members
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
The primary efficacy endpoint is the proportion of subjects in the Per
Protocol (PP) population in each treatment group with treatment Success
at Day 15 ± 2. Treatment Success is defined as an IGA score of 0 (clear)
or 1 (almost clear) within all treatment areas based on the Investigator‟s
Global Assessment of Disease at the end of treatment (week 2, visit 4;
study Day 15).
ï‚· Visit 1: Screening(Day -14 to Day 0)
ï‚· Visit 2 Baseline (Day 0)
ï‚· Visit 3: Interim Visit (Day 4)
 Visit 4: End of Study/Early Termination (Day15 ± 2)
ï‚· Safety Follow up Visit: 7 days after the last application of study
treatment. It can be performed telephonically.
Secondary Outcome
Outcome
TimePoints
The secondary efficacy endpoints are:
1. The proportion of subjects with Treatment Success at Day 15 ±2
2. The change in severity score from baseline to Day 15 ± 2 of the
four individual signs and symptoms of AD (i.e., erythema,
induration/papulation, lichenification, and pruritus).
3. The proportion of participant who have achieved SCORAD
score 15 in SCORAD scale of disease severity.
Visit 1: Screening(Day -14 to Day 0)
ï‚· Visit 2 Baseline (Day 0)
ï‚· Visit 3: Interim Visit (Day 4)
 Visit 4: End of Study/Early Termination (Day15 ± 2)
ï‚· Safety Follow up Visit: 7 days after the last application of study
treatment. It can be performed telephonically.
Target Sample Size
Total Sample Size="501" Sample Size from India="501" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"