CTRI/2022/11/047272 [Registered on: 14/11/2022] Trial Registered Prospectively
Last Modified On:
23/10/2023
Post Graduate Thesis
No
Type of Trial
BA/BE
Type of Study
Study Design
Other
Public Title of Study
Comparison of Tretinoin Cream 0.025% from Encube Ethicals Pvt. India Ltd with RETIN-A (Tretinoin) Cream, 0.025% (Bausch Health US, LLC Bridgewater, NJ 08807 USA) and placebo in the treatment of acne vulgaris.
Scientific Title of Study
A Randomized, Double-Blind, Multicenter, Three arm, Active and Placebo-Controlled, Parallel Design Study to Evaluate the Bioequivalence (with
Clinical Endpoint) of Tretinoin Cream USP, 0.025% of Encube Ethicals Pvt. Ltd., India Versus RETIN-A® (Tretinoin) Cream, 0.025% of Bausch Health US, LLC Bridgewater, NJ 08807 USA in Subjects with Acne Vulgaris.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
Protocol No.: C2A02283 Version: 01 Date: 09 Aug 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Dr Dharmesh Domadia
Designation
Vice President Global Clinical Operation
Affiliation
Cliantha Research Limited
Address
TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad - 382 210, Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
9879590828
Fax
Email
ddomadia@cliantha.com
Details of Contact Person Scientific Query
Name
Dr Ankesh Barnwal
Designation
Associate Director- I– Clinical Trial Medical Services
Affiliation
Cliantha Research Limited
Address
TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad - 382 210, Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
Fax
Email
abarnwal@cliantha.com
Details of Contact Person Public Query
Name
Mr Devesh Verma
Designation
Associate Director-I - Clinical Trials
Affiliation
Cliantha Research Limited
Address
TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad - 382 210, Gujarat, India
Ahmadabad GUJARAT 382210 India
Phone
Fax
Email
dverma@cliantha.com
Source of Monetary or Material Support
Encube Ethicals Private Limited, Unit No. 24, Steelmade Industrial Estate, Marol Village, Andheri (E), Mumbai-400 059, Maharashtra, India.
Primary Sponsor
Name
Encube Ethicals Private Limited
Address
Unit No. 24, Steelmade Industrial Estate, Marol Village, Andheri (E), Mumbai-400 059, Maharashtra, India.
Type of Sponsor
Pharmaceutical industry-Indian
Details of Secondary Sponsor
Name
Address
Cliantha Research Limited
TP 86, FP 28/1, Off S.P. Ring Road, Sarkhej, Ahmedabad - 382 210, Gujarat, India
Star Plus Complex, 4th and 5th, Lam Road, Opp. to NMC,Divisional Office, Near Muktidham Temple, Nasik Road,Nashik – 422101, Maharashtra, India Nashik MAHARASHTRA
9595789893
drtruptis232@gmail.com
Dr Rashmi Mahajan
Baroda ENT & Skin Center
2nd Floor, Siddharth Crest, Nizampura Main Rd,
Vadodara -390024, Gujarat, India Vadodara GUJARAT
9227676607
rsoodmahajan@gmail.com
Dr Bhavarth Kalaria
Care and Cure Multispeciality Hospital
Besides Nilamkunj Society, Nr. Gokulnathji Haveli, Mira Cinema Cross Road, Bhairavnath, Maninagar, Ahmedabad, Gujarat 380028, India. Ahmadabad GUJARAT
1st and 2nd floor, Narayan Resi Complex, near Vaikunth Township,
Gate No. 02, Khodiyar Nagar, New VIP Road, Vadodara – 390018, Gujarat, India Vadodara GUJARAT
9099025287
drkishanninama.dermatologist@gmail.com
Dr Neela Patel
Sheth L. G Municipal General Hospital
Near Rambaug, Maninagar Ahmadabad GUJARAT
9824058208
patelneela1974@yahoo.co.in
Dr Swati Engineer
Shraddha Multispeciality Hospital
Vaibhav Complex, Near Municipal Hospital,
Kalol, Gandhinagar – 382721, Gujarat, India Gandhinagar GUJARAT
VHM healthcare & Research Center LLP, 3rd Floor, Velocity business Hub, Near Madhuvan Circle, LP Savani Road, PAL, Surat - 395009, Gujarat, India Surat GUJARAT
YashSocietysSujata Birla Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: L700||Acne vulgaris,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo Cream (vehicle) for Tretinoin Cream USP, 0.025% of
Encube Ethicals Private Limited, India
Subjects or guardian will be
instructed to apply a small
amount of IP topically once daily at bedtime for 84 consecutive days from Day 0 as per randomization schedule
Comparator Agent
RETIN-A® (Tretinoin) Cream, 0.025%,
Subjects or guardian will be
instructed to apply a small
amount of IP topically once daily at bedtime for 84 consecutive days from Day 0 as per randomization schedule
Intervention
Tretinoin Cream USP, 0.025% of Encube Ethicals Pvt. Ltd., India
Subjects or guardian will be
instructed to apply a small
amount of IP topically once daily at bedtime for 84 consecutive days from Day 0 as per randomization schedule
Inclusion Criteria
Age From
12.00 Year(s)
Age To
40.00 Year(s)
Gender
Both
Details
Subjects will be eligible for inclusion in this study only if all of the following criteria apply:
1. Male or non-pregnant, non-lactating female aged ≥ 12 and ≤ 40 years with a clinical diagnosis of acne vulgaris.
2. On the face, ≥ 25 non-inflammatory lesions (i.e., open and closed comedones) AND ≥ 20 inflammatory lesions (i.e., papules and pustules) AND ≤ 2 nodulocystic lesions (i.e., nodules and cysts).
3. Investigator’s Global Assessment (IGA) of acne severity grade 2, 3 OR 4 (Refer Table 8-2).
4. Willing and able to refrain from use of all other topical products, all acne medications and all antibiotics (other than study treatment) during the 12-week treatment period.
5. Willing to provide written informed consent or assent (as applicable).
6. If female of childbearing potential, willing to use an acceptable form of birth control during the entire study duration.
7. Have used the same brand of make-up for a minimum period of 2 weeks prior to randomization, for subjects who use make-up and agree to not change make-up brands or types during the study.
8. Subject who received COVID-19 vaccine should have recovered from vaccine related side effects prior to screening.
ExclusionCriteria
Details
Subjects will be eligible for inclusion in this study only if all of the following criteria apply:
1. Male or non-pregnant, non-lactating female aged ≥ 12 and ≤ 40 years with a clinical diagnosis of acne vulgaris.
2. On the face, ≥ 25 non-inflammatory lesions (i.e., open and closed comedones) AND ≥ 20 inflammatory lesions (i.e., papules and pustules) AND ≤ 2 nodulocystic lesions (i.e., nodules and cysts).
3. Investigator’s Global Assessment (IGA) of acne severity grade 2, 3 OR 4 (Refer Table 8-2).
4. Willing and able to refrain from use of all other topical products, all acne medications and all antibiotics (other than study treatment) during the 12-week treatment period.
5. Willing to provide written informed consent or assent (as applicable).
6. If female of childbearing potential, willing to use an acceptable form of birth control during the entire study duration.
7. Have used the same brand of make-up for a minimum period of 2 weeks prior to randomization, for subjects who use make-up and agree to not change make-up brands or types during the study.
8. Subject who received COVID-19 vaccine should have recovered from vaccine related side effects prior to screening.
Exclusion Criteria:
Subjects will not be eligible for inclusion in this study if any of the following criteria apply:
1. Female who is breastfeeding, pregnant or planning to become pregnant.
2. Subject who has acne conglobata, acne fulminans, nodulocystic acne and secondary acne (e.g., chloracne and drug induced acne).
3. Subject who has clear symptoms of severe or intense irritation on the face.
4. Presence of any skin condition that would interfere with the diagnosis or assessment of acne vulgaris (e.g., on the face: rosacea, dermatitis, psoriasis, squamous cell carcinoma, eczema, acne form eruptions caused by medications, steroid acne, steroid folliculitis, or bacterial folliculitis).
5. Excessive facial hair (e.g., beards, sideburns, moustaches, etc.) that would interfere with the diagnosis or assessment of acne vulgaris. Well-trimmed moustaches are allowed.
6. History of hypersensitivity or allergy to tretinoin, retinoids, or any of the investigational product ingredients.
7. Use within 6 months prior to the baseline of oral retinoids (e.g., Accutane®) or therapeutic Vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed).
8. Use for less than 3 months prior to the baseline of estrogens or oral contraceptives; use of such therapy must remain constant throughout the study.
9. Use on the face within 1 month prior to baseline of 1) Cryodestruction or Chemodestruction, 2) Dermabrasion, 3) Photodynamic therapy, 4) Acne surgery, 5) Intralesional steroids, or 6) X-ray therapy.
10. Use within 1 month prior to baseline of 1) Spironolactone 2) Systemic steroids 3) Systemic (e.g., oral or injectable) antibiotics 4) Systemic treatment for acne vulgaris (other than oral retinoids which require a 6-month washout) or 5) Systemic anti-inflammatory agents or immunosuppressive drugs.
11. Use within 2 weeks prior to baseline of 1) Topical steroids, 2) Topical retinoid 3) Topical acne treatments including over-the-counter preparations 4) Topical anti-inflammatory agents, or 5) Topical antibiotics 6) Astringents and toners 7) abradants, facials, peels containing glycolic or other acids 8) masks 9) washes or soaps containing benzoyl peroxide, salicylic acid, or sulfacetamide sodium 10) non-mild facial cleansers 11) moisturizers that contained retinol 12) moisturizers that contained retinol, salicylic acid or α- or β-hydroxy acids.
12. Concomitant use/planned to use of mega-doses of certain vitamins (such as vitamin D [> 2000 IU/day], vitamin B6 [> 2 mg/day] and vitamin B12 [> 1 mg/day]), haloperidol, halogens such as iodide and bromide, lithium, hydantoin and phenobarbital.
13. A significant medical history of or are currently immunocompromised or receiving immunomodulators/biologics since last 3 months.
14. Subject who has been treated with an investigational product or investigational device within a period of 30 days prior to study enrollment.
15. Have any systemic or dermatologic disease that may affect the evaluation of study results.
16. Subject who has been previously enrolled in this study.
17. Subject who engage in activities that involve excessive or prolonged exposure to sunlight or weather extremes, such as wind or cold.
18. Current drug abuse (including, but not limited to, cannabinoids and cocaine) or alcohol abuse (greater than two drinks per day) or relevant abuse history (within the past year).
19. Subject with any application site reaction assessment score 3 (severe, marked/intense). (Refer to Table 8-3)
20. Use of Anti-pruritic, including antihistamines, within 24 hours of baseline visit.
21. Use of tanning booths or tanning lamps within one week prior to baseline and an unwillingness to refrain from use during the study.
22. Subject with clinically significant unstable medical disorders, life-threatening disease, or current malignancies.
23. Subject with signs and symptoms suggestive of COVID 19 infection.
24. Institutionalized subject.
25. Living in the same household of a subject who is currently participating or living in the same household of a subject who has previously participated in the study.
26. Clinically significant abnormal findings or condition (other than acne vulgaris), which might, in the opinion of the Investigator, interfere with study evaluations or pose a risk to subject safety during the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Mean percent change from baseline to Week 12 (Day 84) for inflammatory (papules and pustules) lesion count.
2. Mean percent change from baseline to Week 12 (Day 84) in the non-inflammatory (open and closed comedones) lesion count.
Mean percent change from baseline to Week 12 (Day 84)
Secondary Outcome
Outcome
TimePoints
Proportion of subjects with a clinical response (IGA) of “Success†at Week 12.
Note: Success will be defined as an IGA score that is at least 2 grades less than the baseline assessment. Failure will be defined as an IGA score that is the same, higher or one grade lower than the baseline assessment.
Change from baseline to Week 12 (Day 84)
Target Sample Size
Total Sample Size="1060" Sample Size from India="1060" Final Enrollment numbers achieved (Total)= "1060" Final Enrollment numbers achieved (India)="1060"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This clinical trial intended to Evaluate the Efficacy and
Safety of Tretinoin cream USP, 0.025%) of Encube Ethicals Pvt. Ltd., India with
reference product (RETIN-A® Cream, 0.025%) of Bausch Health US, LLC
Bridgewater, NJ 08807 USA. in Subjects with Acne Vulgaris.
Objectives:
1.To evaluate bioequivalence (with clinical
endpoint) of test product (Tretinoin Cream USP, 0.025%) of Encube Ethicals Pvt.
Ltd., India with reference product (RETIN-A® Cream, 0.25%) of Bausch
Health US, LLC Bridgewater, NJ 08807 USA.
2.To evaluate the superiority in efficacy of
test and reference products over the placebo.
3.To assess safety and tolerability of the
study treatments.
Number of Subjects:
Approximately 1060 subjects shall
be enrolled/randomized into the study with 2:2:1 allocation ratio (i.e. Test
product: 424 subjects, Reference product: 424 subjects and Placebo: 212 subjects).
Clinical evaluations will be
performed at the following visits:
Visit 1#: Screening visit (Up to 3
Days prior to Randomization)