Bioequivalence Study of Pimecrolimus cream in Atopic dermatitis patients
Scientific Title of Study
A Randomized, Double-Blind, Placebo-Controlled, three arms Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic Equivalence and Safety of PimecrolimusCream, 1% (Encube Ethicals Private Limited)withElidel® (Pimecrolimus) Cream, 1% (Valeant PharmaceuticalsNorth America LLC) in the Treatment of Mild to Moderate Atopic Dermatitis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
ARL/CT/18/003
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Manufactured by: Valeant Pharmaceuticals North America
LLCs
Application:The study product will be applied in a thin layer to the affected areas twice daily (morning and evening).
Intervention
Pimecrolimus Cream, 1%
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).
Comparator Agent
Vehicle for Pimecrolimus Cream, 1%
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
12.00 Year(s)
Age To
75.00 Year(s)
Gender
Both
Details
1. Non-immunocompromised male or non-pregnant, non-lactating female aged 12 years and older with a clinical diagnosis of mild to moderate atopic at the time of signing the informed consent.
2. Subjects have confirmed diagnosis of atopic dermatitis for at least 3 months.
3. Subject with clinical diagnosis of mild to moderate atopic 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. Subjects having an Investigator’s Global Assessment(IGA) of disease severity of mild or moderate at baseline. [a score of 2 (mild) or 3 (moderate)]and SCORAD score of disease severity should be in > 15 and <50.
5. Subjects having an affected area of AD involvement of at least 5% Body Surface Area (BSA) at baseline, as defined by the Hanifin and Rajkacriteria.
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. Subject treated with a bland emollient for at least 7 days prior to baseline.
8. 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 study and 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.
9. 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) in the areas to be treated, except for bland emollient (moisturizer).
11. Known allergy or hypersensitivity to Pimecrolimusor 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 conditions 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 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 global assessment of disease at the end of treatment (week 4, study day 15)
Visit 1: Screening(Including 7 days run in period, subjects will
start the bland emollient immediately from the screening day
itself)
ï‚· Visit 2 Baseline (Day 0)
 Visit 3: Interim Visit (Day 8 ± 2)
 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 ± 2of 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(Including 7 days run in period, subjects will
start the bland emollient immediately from the screening day
itself)
ï‚· Visit 2 Baseline (Day 0)
 Visit 3: Interim Visit (Day 8 ± 2)
 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="588" Sample Size from India="588" Final Enrollment numbers achieved (Total)= "588" Final Enrollment numbers achieved (India)="588"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
Its a Randomized, Double-Blind, Placebo-Controlled, three arms Parallel-Design, Multiple-Site Study to Evaluate the Therapeutic Equivalence and Safety of Pimecrolimus Cream, 1% (Encube Ethicals Private Limited)with Elidel® (Pimecrolimus) Cream, 1% (Valeant Pharmaceuticals North America LLC) in the Treatment of Mild to Moderate Atopic Dermatitis.
Approximately 588 males and non-pregnant females, 12 years of age and older, with mild to moderate Atopic Dermatitis.
Subject will have to do four clinic visit during the total duration of the study. The visit will include Visit 1 Screening visit, Visit 2 Randomization visit, Visit 3 Interim Visit and Visit 4 End of study/Early Termination visit.
Safety Evaluations will be performed in accordance with the study schematic. Safety assessments will include monitoring of adverse events (AEs) and application site reactions, vital sign measurements, urine pregnancy tests (for all women of childbearing potential).