A Double-Blind, Randomized, Placebo-Controlled, Three-Arm, Parallel-Group, Multi-Centre Clinical Study to evaluate the Safety and Clinical Endpoint Bioequivalence of Tacrolimus Ointment 0.1% w/w of JAMP Pharma Corporation, Canada and PrProtopic® tacrolimus ointment, 0.1% (w/w) of LEO Pharma Inc., Toronto, ON, M2H 3S8 and Compare Both Active Treatments to a Placebo Control in the Treatment of Non-immunocompromised Patients with Moderate to Severe Atopic Dermatitis.
Trial Acronym
NA
Secondary IDs if Any
Secondary ID
Identifier
iVRS-CD-22-065, Version 01, dated 21 Feb 2023
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Shendkar Sonal Mahadev
Designation
MBBS, DDV
Affiliation
Lifepoint Multispeciality Hospital
Address
Lifepoint Multispeciality Hospital,3rd floor, Clinical Research Department
145/1 Mumbai Bangalore Highway, Near Hotel Sayaji Wakad Pune 411057 Maharashtra
Pune MAHARASHTRA 411057 India
Phone
9960178611
Fax
Email
shendkar.sonal82@gmail.com
Details of Contact Person Scientific Query
Name
Dr Channa Basavanna G Halasagi
Designation
Medical Monitor
Affiliation
Invitro Research Solutions Pvt. Ltd
Address
Invitro Research Solutions Pvt. Ltd, Clinical Development
Department, Medical Monitoring Divison, Room No 301, 3rd Floor
No. 22 & 23, Kodigehalli Main Road, Sahakar Nagar Post,
Hebbal,Bangalore
Bangalore KARNATAKA 560092 India
Phone
6366947473
Fax
Email
channa@ivrs.org.in
Details of Contact Person Public Query
Name
T Vijay Bhaskar
Designation
Director- Clinical Development
Affiliation
Invitro Research Solutions Pvt. Ltd
Address
Invitro Research Solutions Pvt. Ltd, Clinical Development
Department, Clinical Operations Divison, 2nd Floor No. 22 & 23,Kodigehalli Main Road, Sahakar Nagar Post, Hebbal,Bangalore
Government Medical College & Government General Hospital (Old RIMSGGH)
Government Medical College & Government General Hospital (Old RIMSGGH),
Srikakulam-532001,
Andhra Pradesh, India Srikakulam ANDHRA PRADESH
9908066043
drrevathivggh@gmail.com
Dr Sowmya C S
KIMS Hospital and Research Center
B Block, Skin OPD, 2nd Floor, Department of Dermatology, K.R. Road, V.V. Puram, Bangalore-560004, Karnataka, India Bangalore KARNATAKA
9611116181
sowmya.cs21@gmail.com
Dr Kinjal Bharat Mistry
KKasturi Medicare Pvt. Ltd.,
Room number 04, Ground floor, Department of Dermatology, OPD Building, Harshniketan, Gaondevi Road, Behind Navrang Hotel, Bhayandar West, Dist-Thane-401101, Maharashtra, India Thane MAHARASHTRA
8356003006
drkinjalmistry04@gmail.com
Dr Bangaru H
KR Hospital
Room number 14,1st floor,
Department of Dermatology,
OPD Building,
KR Hospital, Mysore Medical College and Research Institute, Irwin Road, Mysore- 570001, Karnataka, India Mysore KARNATAKA
9886789231
drbangaruskin@gmail.com
Dr Vipul Gupta
KRM Hospital and Research Centre
Room number 2,Ground floor, Department of Dermatology, OPD Building, KRM Hospital and Research Centre, 3/92-93 Vijyant Khand, Gomti Nagar, Lucknow-226010, Uttar Pradesh, India Lucknow UTTAR PRADESH
9005044010
krmhrclko@gmail.com
Dr Ishad Agarwal
Lifeline Diagnostic Center cum Nursing Home
2nd floor, Department of Dermatology, OPD Building, 4A, wood street Kolkata 700016 West Bengal, India Kolkata WEST BENGAL
8100622846
ishad1984@gmail.com
Dr Sonal Shendkar
Lifepoint Multispecialty Hospital
Room number 02,1st floor, Department of Dermatology, OPD Building, 145/1, Mumbai Bangalore Highway, Near Hotel Sayaji, Wakad, Pune – 411057, Maharashtra, India. Pune MAHARASHTRA
9960178611
shendkar.sonal82@gmail.com
Dr Grandhi Sudhakarrao Venkata
Medipoint Hospitals Pvt Ltd
Room number 01,1st floor, Department of Dermatology, OPD Building, 241/1, New D.P. Road, Aundh, Pune – 411007, Maharashtra, India. Pune MAHARASHTRA
9850082614
sudhakargrandhi.pentagon@gmail.com
Dr Hemantkumar Vasantrao Talnikar
Oyster and Pearl Hospitals (Phadnis Clinic Pvt Ltd)
5th Floor, Room No. 504, Clinical Research Department, 1671-75,Ganeshkhind Road, Shivajinagar, Pune- 411005, Maharashtra, India
Pune MAHARASHTRA
9657890464
drhemantkumart@gmail.com
Dr Savitha A S
Rajalakshmi Hospital
3rd Floor, Department of Dermatology, OPD Building,#21/1, Lakshmipura Main Road, Vidyaranyapura Post, Bangalore- 560097, Karnataka, India Bangalore KARNATAKA
9880512166
drsavithasomaiah@gmail.com
Dr Adarsh Gowda
Santosh Hospital
Department of Dermatology,
OPD Building,6/1,PROMENADE ROAD, NEAR COLES
PARK,FRAZER TOWN, Bangalore- 560005, Karnataka, India Bangalore KARNATAKA
9686100333
adarshgowda@hotmail.com
Dr Eswari L
Shettys Hospital
Room number 102,Ground floor, Department of Dermatology, OPD Building, Plot No. 11 & 12, 12th F main Road, Kaveri Nagar, Bommanahalli, Bangalore-560068, Karnataka, India Bangalore KARNATAKA
8123851615
dreswaril123@gmail.com
Dr Rashmi Singh
Shubham Sudbhawana Superspeciality Hospital
Room number 06, 1st Floor, Department of Dermatology, OPD Building, B31/80,23 B- Bhogabir, Lanka Varanasi- 221005, Uttar Pradesh, India. Varanasi UTTAR PRADESH
9386233538
sweetrashmi4364@gmail.com
Dr Harish Prasad B R
Sri Venkateshwara Hospital
Room number 206,1st floor, Department of Dermatology, OPD Building, Sky Heights, Site No.1/2, Sarjapura-Attibele Main Road, Indelebele village, Bangalore-562107, Karnataka, India Bangalore KARNATAKA
9738389028
harishprasadbr@gmail.com
Dr Sunil Kumar S
Vagus Super Speciality Hospital
Department of Dermatology, OPD Building, 6,7 and 8, 18th Cross, 4th Main, Malleshwaram, Bangalore-560055, Karnataka, India. Bangalore KARNATAKA
Patients will topically apply a thin layer of ointment to affected skin areas and rub in gently and completely so that the medication is applied to all the affected areas that the investigator
has diagnosed as AD. Study medication will be applied twice daily, with at least 12 hours between the two applications, for 14 days (2 weeks).
Comparator Agent
Reference Product (R): PrProtopic® tacrolimus ointment, 0.1% (w/w) of LEO Pharma
Inc., Toronto, ON, M2H 3S8
Patients will topically apply a thin layer of ointment to affected skin areas and rub in gently and completely so that the medication is applied to all the affected areas that the investigator has diagnosed as AD. Study medication will be applied twice daily, with at least 12 hours between the two applications, for 14 days (2 weeks).
Intervention
Test product (T): Tacrolimus Ointment 0.1% w/w of JAMP Pharma Corporation, Canada.
Patients will topically apply a thin layer of ointment to affected skin areas and rub in gently and completely so that the medication is applied to all the affected areas that the investigator has diagnosed as AD. Study medication will be applied twice daily, with at least 12 hours between the two applications, for 14 days (2 weeks).
Inclusion Criteria
Age From
12.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
1. Non-immunocompromised male or female patients, greater than or equal to 12 years of age.
2. Has a definite clinical diagnosis of moderate to severe atopic dermatitis for at least 3 months with greater than or equal to 20% BSA being affected at baseline as defined by the criteria of Hanifin and Rajka.
3. Has, according to the Hanifin and Rajka Criteria, at least three of the following,itching, chronic relapsing course, typical morphology and distribution of lesions (ie, flexural lichenification and linearity in adults; facial and extensor involvement during infancy and childhood), or familial and/or personal history of
other atopic disorders (ie, asthma, allergic rhino-conjunctivitis, atopic dermatitis)
4. Has a Baseline Investigators Global Assessment score of at least moderate greater than or equal to 3.
5. Has moderate to severe atopic dermatitis for which the use of alternative, conventional therapies are deemed inadvisable because of potential risks, or are not adequately responsive or are intolerant to other topical prescription treatments for AD or alternative, conventional therapies.
6. In case of female patients with childbearing potential (a female who is not postmenopausal for greater than 2 years and has not undergone a tubal ligation or a hysterectomy), the patient should have a negative urine pregnancy test at
screening and should be willing to use an acceptable form of birth control during
the study.
7. Patients willing to provide a study specific Institutional Review Board (IRB) approved written informed consent for this study.
8. Patients willing and able to understand and comply with the requirements of the study, apply the study medication as instructed, return for the required treatment period visits, comply with therapy prohibitions, and complete the study.
9. Patients who agree to adhere to protocol-specified requirements and concomitant
therapy restrictions during the study, including discontinuation of non-medicated topical agents such as creams, lotions, and emollients (to treatment area); topical antihistamines; topical antimicrobials; topical antifungals; topical or systemic corticosteroids; light treatments (ultraviolet A [UVA], UVB); non-steroid
immunosuppressants; and other investigational drugs.
10. Patients who are otherwise in good health, as confirmed by medical history and physical examination, and free from any clinically significant disease, other than atopic dermatitis, that might interfere with the study evaluations.
11. Has a physical condition which enable patients to be fit for a Pharmacokinetic sampling, according to principal investigator evaluation
ExclusionCriteria
Details
1. Female patients who are pregnant, nursing, or planning a pregnancy within the study participation period.
2. Has clinically infected atopic dermatitis at Baseline i.e., Active cutaneous bacterial or viral infection in any treatment area at the baseline.
3. Has a skin disorder other than atopic dermatitis or history or presence of skin disorders that may interfere with the study evaluations (ie, Netherton’s Syndrome, psoriasis, rosacea, topical fungal infections, erythroderma or ichthyosis, etc.).
4. Has sunburn, pigmentation, extensive scarring, or pigmented lesions in the proposed treatment areas at the baseline, which could interfere with the rating of efficacy parameters.
5. Has known or suspected history or presence of a clinically significant systemic disease (ie, immunological deficiencies, human immunodeficiency virus [HIV]), unstable or not controlled medical disorders (ie, unstable diabetes, unstable hypertension), life threatening disease, or current malignancies, serious active or recurrent infection or clinically significant severe renal insufficiency or severe hepatic disorders or any other significant medical condition likely to compromise participation in the study or the outcome of assessments, or to place the patient at risk.
6. Has been treated with photo anti-psoriatic therapies/drugs, UVA/UVB therapy, psoralen plus ultraviolet A (PUVA) therapy, tanning booths, non-prescription UV light sources, immunomodulators or immunosuppressive therapies, interferon, cytotoxic drugs, tacrolimus, or pimecrolimus within 1 month prior to study entry.
7. Has taken systemic corticosteroids (ie, oral or intravenous or intramuscular) within the past 1 month.
8. Has been treated with any marketed or investigational biologic treatment for psoriasis or atopic disease (eg, alefacept, efalizumab, infliximab, adalimumab, etanercept, etc.) within the past three months or five half-lives of the biologic, whichever is longer. Vaccinations will not be considered as an exclusionary biologic treatment.
9. Has been treated within 14 days of baseline with any of: systemic antibiotics, calcipotriene or other vitamin D preparations, or retinoids.
10. Has applied topical antimicrobials, topical or oral antihistamines, topical corticosteroids, topical antifungals or other medicated topical agents to the affected areas within the past seven days.
11. Has applied any topical agents (including creams, ointments, gels, lotions, and emollients) in the areas to be treated within the previous 24 hours.
12. Patients who are currently using calcium channel blockers (e.g, amlodipine, nifedipine, verapamil, diltiazem, felodipine, isradipine, nisoldipine, etc) and/or cimetidine which are CPY3A inhibitors.
13. Has a known hypersensitivity to any of the following (in any dosage form): tacrolimus, macrolides (i.e., erythromycin), or any excipient of the ointment.
14. Patients who are not willing to avoid constant sun exposure and the use of tanning booths or other UV light sources during their participation in the study.
15. Patients who tend consume excessive amounts of alcohol, abuse drugs, or has any condition that would compromise compliance, in the investigator’s opinion, with the protocol.
16. Has been treated with an investigational drug or investigational device within a period of 30 days prior to study entry.
17. Any history of difficulty in accessing veins to draw blood
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator and Outcome Assessor Blinded
Primary Outcome
Outcome
TimePoints
The primary endpoint is the proportion of patients in the Per Protocol (PP) population in each treatment group with treatment success (i.e., a grade of clear or almost clear, a score of 0 or 1, within all treatment areas) based on the Investigator’s Global Assessment of Disease Severity at the end of treatment.
From baseline to Day 4, Day 7 & Day 15
Secondary Outcome
Outcome
TimePoints
The secondary endpoints are change in severity from baseline to Week 2 (Study
Day 15) of four individual signs and symptoms of AD (i.e., erythema,
induration/papulation, lichenification and pruritus) and are considered supportive
information.
From baseline to Day 4, Day 7 & Day 15
Target Sample Size
Total Sample Size="450" Sample Size from India="450" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="0"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This study is a Double-Blind, Randomized, Placebo-Controlled, Three-Arm, Parallel-Group, Multi-Centre Clinical Study to evaluate the Safety and Clinical Endpoint Bioequivalence of Tacrolimus Ointment 0.1% w/w of JAMP Pharma Corporation, Canada and PrProtopic® tacrolimus ointment, 0.1% (w/w) of LEO Pharma Inc., Thornhill, Ontario, L3T 7W8 and Compare Both Active Treatments to a Placebo Control in the Treatment of Non-immunocompromised Patients with Moderate to Severe Atopic Dermatitis. for this study No. of subjects is 450,180 subjects for Test, 180 subjects for Reference and 90 subjects for Placebo, Where the primary endpoint is the proportion of patients in the Per Protocol (PP) population in each treatment group with treatment success (i.e., a grade of clear or almost clear, a score of 0 or 1, within all treatment areas) based on the Investigator’s Global Assessment of Disease Severity at the end of treatment (Week 2 visit: Study Day 15) and the secondary endpoints are change in severity from baseline to Week 2 (Study Day 15) of four individual signs and symptoms of AD (i.e., erythema, induration/papulation, lichenification and pruritus) and are considered supportive information.