Randomized, double-blind, placebo-controlled, three-arm parallel design, multiple-site bioequivalence study with clinical endpoints
Scientific Title of Study
A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Three-arm, Parallel Study to Evaluate the Bioequivalence using Clinical Endpoint of Tretinoin Gel microsphere, 0.08% (Encube Ethicals Private Limited, India) to Retin-A Micro (tretinoin) Gel microsphere 0.08% (Valeant Pharmaceuticals North America LLC, NJ 08807) in Subjects with Acne Vulgaris
Skin Department OPD, 2nd Floor,MMF Joshi Hospital, 778, Shivajinagar, Opposite Kamala Nehru park, Pune- 411004, Maharashtra, India. Pune MAHARASHTRA
08793226922
deshpandeajay.68@gmail.com
Dr Saikia Siddhartha Satyakant
Anand Multispecialty Hospital and Research Centre
Clinical Research Department,4th Floor, Sarthak mall, Mahatma Mandir Road, Sargasan cross road, Gandhinagar-382421, Gujarat, India Gandhinagar GUJARAT
8511511273
anandhospital.rc@gmail.com
Dr Kalambe Vaibhav Anand
Asian Institute of Medical Sciences (AIMS)
General OPD, 1st Floor Asian Institute of Medical Science, P-72 Milap Nagar, MIDC, Dombivli (E) 421203, Maharashtra, India. Thane MAHARASHTRA
09167551456
drvaibhavkalambe@gmail.com
Dr Madhu Shah
Bodyline Hospital
Clinical Research Department (Basement), Opposite Annapurna Hall, Dev Status, Near Vikas Gruh road, Paladi, Ahmedabad-380007, Gujarat, India Ahmadabad GUJARAT
9824076703
bodylinehospitalcrc@gmail.com
Dr Meenal M Bhirud
Dhadiwal Hospital in coaliation with Shreeji Healthcare
Clinical Research Department, Oppsite New CBS, Trimbak road, Nashik, Maharashtra, India. Nashik MAHARASHTRA
Department of Dermatology,Opposite DRM office, Near Chamunda Bridge, Naroda Road, Ahmedabad-380025, Gujarat, India Ahmadabad GUJARAT
9925011309
patelnayan78.np@gmail.com
Dr Prashant Palwade
Ishwar Institute of Health care
Clinical Research Department,Ishwar heights, Plot no 7, Gut no 6/1, beside Punjabi bhawan, Padegaon, Aurangabad-431002, Maharashtra, India Aurangabad MAHARASHTRA
9323707031
prashantpalwade@gmail.com
Dr Kapadia Saurabh Dineshchandra
Kanoria Hospital and Research Centre
Clinical Research Department (Ground Floor),Airport-Gandhinagar highway, Village- Bhat, Gandhinagar Dist-382428, Gujarat, India Gandhinagar GUJARAT
9824261031
drsaurabhkapadia@yahoo.com
Dr Adarsh Gowda
Kempegowda Institute of Medical Sciences
KIMS Hospital, Department of Dermatology
B Block, 2nd Floor, OPD Building
Room no 10, K R Road, V V Puram
Bangalore-560004, Karnataka, India.
Bangalore KARNATAKA
09686100333
adarshgowda@hotmail.com
Dr Shivakumar Patil
KLE Dr. Prabhakar Kore Hospital & Medical Research Centre
Clinical Research Department, Nehru Nagar, Belgaum – 590010
Karnataka, India.
Belgaum KARNATAKA
9844512315
shivakumarkpatil@gmail.com
Dr Nanjundaswamy BL
KR Hospital attached to Mysore Medical College and Research
KR Hospital attached to Mysore Clinical Research Department, Medical College and Research Institute, Irwin road, Mysore – 570001, Karnataka, India. Mysore KARNATAKA
9448025219
drblnswami@gmail.com
Dr Balakrishna Nikam
Krishna institute of Medical Sciences
Clinical Research Department,Pune Bangalore highway NH-4, Malkapur road, Near Dhebewadi Phata, Malkapur, Karad-415539, Dist-Satara, Maharashtra, India. Satara MAHARASHTRA
9322373096
mangeshnikam@yahoo.com
Dr Sonal Mahadev Shendkar
Lifepoint Multispecialty Hospital
Research OPD, First floor, 145/1,
Mumbai Bangalore Highway, Near Hotel Sayaji, Wakad, Pune-411057, Maharashtra, India.
Pune MAHARASHTRA
Room no 10, 2nd Floor, B-Block, Lokmanya Holistic Cancer Care and Research Center, Telco Raod, Chinchiwad, Pune - 411033 Pune MAHARASHTRA
08805139534
hemant.vasant16@gmail.com
Dr Rajeev Agarwal
M. V. Hospital and Research Centre
Clinical Research Department, 314/30, Mirza Mandi chowk
Lucknow - 226003
Uttar Pradesh, India
Lucknow UTTAR PRADESH
9415080604 05224016051 mvhrclko@gmail.com
Dr Maheshkumar Chaturbhai patel
Medistar Multispecialty Hospital
Clinical Research Department, 1, Trimurti Avnenue, Medistar Cross road, Industrial area, Himatnagar-383001, Gujarat, India Sabar Kantha GUJARAT
9228244966
maheshpatel1975@yahoo.com
Dr Dipak Amrutbhai Patel
Nirmal Hospital Pvt Ltd
Consultant Dermatologist, Adult OPD, Ring Road, Surat – 395002, Gujarat, India. Surat GUJARAT
09374711540
drdipakapatel@gmail.com
Dr Sarita AbhaykumarTippannawar
Oyster and Pearl hospitals
Clinical Research Department, Oyster and Pearl hospitals, 1671-75, Ganeshkhind road, Shivajinagar, Pune-411005, Maharashtra, India Pune MAHARASHTRA
9370665436
drrita.0709@gmail.com
Dr Shah Ruchir Hitendrabhai
Sanjivini Super Specialty Hospital Pvt. Ltd
Clinical Research Department, 1, Uday Park Society, Nr Sunrise Park, Vastrapur, Ahmedabad-380015, Gujarat, India Ahmadabad GUJARAT
9904079691
drruchirshah.dermatologist@gmail.com
Dr Smita Anish Nagpal
Saviour Multispecialty Hospital
Clinical Research Department,Near Bharath Petrol pump, near Lakhudi talav, Stadium road, Navrangpur, Ahmedabad-380014, Gujarat, India Ahmadabad GUJARAT
9825721525
nagpalsmita@gmail.com
Dr Harish Prasad BR
Shetty’s Hospital
Clinical Research Department, Plot no 11, 12, 12th F main, Kaveri Nagar, Bommanahalli, Kodichikkanahalli, Bangalore – 560068, Karnataka, India
Bangalore KARNATAKA
9738389028 08025732887 shettyhospital@gmail.com
Dr Bhavsar Bhavik kumar Arvindbhai
Shivam hospital
Clinical Research Department,C/4 Satyanarayana Society, gor’s Kuva, near Jashodhanagar char rasta, Maninagar (E), Ahmedabad-380008, Gujarat, India Ahmadabad GUJARAT
9825953263
bhavik.bhavsar78@gmail.com
Dr Chetan Lalseta
Shree Giriraj Multispeciality Hosptial
Dept of Dermatology, 150 feet Ring Road, 27, Navjyot Park Main Road, Amin Marg Cross Road- 360005
Rajkot, Gujarat, India.
Rajkot GUJARAT
9825199585
chetanlaseta@gmail.com
Dr Rohit Batra
Sir Ganga Ram Hospital
Department of Dermatology, Room no 89, First floo, SGRH Marg, Rajinder Nagar,
New Delhi -110060
Delhi, India
New Delhi DELHI
09911200050
drrohitbatra@gmail.com
Dr Sunil Kumar Prabhu
Sri Venkateshwara Hospitals
Clinical Research Department, 27, 29th main road, Rashtra Kuvempu nagar, BTM 2nd stage, BTM layout, Bangalore – 560076, Karnataka, India Bangalore KARNATAKA
9880447921 08025630006 svhospital1997@gmail.com
Dr Rashmi Singh
Sudhbhawana Hospital
Department of Dermatology, First floor, B31/80-23 B -Bhogabir,
Lanka Varanasi-221005
Uttar Pradesh, India
Varanasi UTTAR PRADESH
09386233538
sweetrashmi4364@gmail.com
Dr Suneel Vartak
Sujata Birla Hospital and Medical Research Center
3rd floor, Clinical Research Department, Sujata Birla Hospital and Medical Research Center, Opposite Bytco College, Nashik Pune Highway, Nashik – 422101, Maharashtra, India. Nashik MAHARASHTRA
09373901829
Suneel.vartak@gmail.com
Dr Rashmi Mahajan
Sumandeep Vidyapeeth & Dhiraj General Hospital
Department of Skin and Veneral disease, At and Po Piparia, Waghodia, Vadodara 391760, Gujarat, India Vadodara GUJARAT
9227676607
researchrav@gmail.com
Dr Deepak Bhalchandra Kotkar
Supe Heart and Diabetes Hospital and Research Centre
Clinical Research Department, Near Rungtha High School,
Gharapure Ghat Rd, Ashok Stambh
Nashik - 422002
Maharashtra, India
Nashik MAHARASHTRA
Dose: As applicable to apply thin layer of study medication to the affected area Frequency: Once daily Route of administration: Topical application Duration of therapy: 84 consecutive days Details: Subjects are instructed to cleanse the face with a mild or soapless, non-medicated cleanser, dry skin gently, wait for 20 to 30 minutes before applying the study medication, and then apply enough product to lightly cover the entire affected areas of the face once daily at bedtime for 84 consecutive days
Comparator Agent
Retin-A Micro® (tretinoin) Gel microsphere 0.08%
Dose: As applicable to apply thin layer of study medication to the affected area Frequency: Once daily Route of administration: Topical application Duration of therapy: 84 consecutive days Details: Subjects are instructed to cleanse the face with a mild or soapless, non-medicated cleanser, dry skin gently, wait for 20 to 30 minutes before applying the study medication, and then apply enough product to lightly cover the entire affected areas of the face once daily at bedtime for 84 consecutive days
Intervention
Tretinoin Gel microsphere, 0.08%
Dose: As applicable to apply thin layer of study medication to the affected area Frequency: Once daily Route of administration: Topical application Duration of therapy: 84 consecutive days Details: Subjects are instructed to cleanse the face with a mild or soapless, non-medicated cleanser, dry skin gently, wait for 20 to 30 minutes before applying the study medication, and then apply enough product to lightly cover the entire affected areas of the face once daily at bedtime for 84 consecutive days
Inclusion Criteria
Age From
12.00 Year(s)
Age To
40.00 Year(s)
Gender
Both
Details
1. Healthy male or non-pregnant, non- lactating female aged ≥ 12 and ≤ 40 years with a clinical diagnosis of Acne vulgaris (AV).
2. On the face, having ≥ 20 inflammatory (i.e., papules and pustules), ≥ 25 non-inflammatory (i.e., open and closed comedones) lesions and ≤ 2 nodulocystic lesions (i.e, nodules and cysts).
3.Investigator’s Global Assessment (IGA) of acne severity grade 2, 3 or 4.
4.Willing to refrain from use of all other topical products (moisturizer, new brands of make-up, creams, lotions, powders or any other topical product), all acne medications and antibiotics during the 12 weeks treatment period.
5.Female subjects of child bearing potential practicing an approved method of contraception and willing to continue its use from study entry to 7 days after the administration of study drug and have a negative Urine Pregnancy Test at the time of screening
or
Female subjects of non-child bearing potential.
Note: Approved methods of contraception include Hormonal contraception including oral, systemic injectable or Intra-uterine Contraceptive Devices must have been on a stable dose for 3 months prior to study entry, bilateral tubal ligation or tubectomy, non-hormonal IUCD, double barrier or strict abstinence.
Use of oral contraceptive therapy is allowed if it shall remain constant throughout the study. Non-child bearing potential is defined as pre-menarche, postmenopausal absence of menstrual bleeding for 1 year prior to enrolment, hysterectomy or bilateral oophorectomy.
6. Male subjects must use accepted methods of birth control or must agree to practice abstinence from study entry to 7 days after the administration of study drug.
7. Willing to provide written informed consent or assent, as applicable. For subjects who are considered minors (< 18 completed years), the parent or legal guardian shall sign the consent form and the child shall be required to sign a subject “assent†form, as appropriate
ExclusionCriteria
Details
1. 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, acneform eruptions caused by medications, steroid acne, steroid folliculitis, or bacterial folliculitis).
2. Excessive facial hair (e.g. beards, sideburns, moustaches, etc.) that shall interfere with diagnosis or assessment of acne vulgaris. Well-trimmed moustaches are allowed.
3. History of hypersensitivity or allergy to tretinoin, retinoids and/or any of the study medication ingredients.
4. Use within 6 months prior to baseline (Randomisation) of oral retinoids (e.g. Accutane®) or therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed).
5. Use for less than 3 months prior to baseline (Randomisation) of estrogens or oral contraceptives or any other hormonal therapy; use of such therapy is allowed if it shall remain constant throughout the study.
6. Use on the face within 1 month prior to baseline (Randomisation) cryo-destruction or chemo-destruction, dermabrasion / microdermabrasion, photodynamic therapy, acne surgery, intralesional steroids, X-ray therapy, chemical or laser peel.
7. Use within 1 month prior to baseline (Randomisation) of androgen receptor blockers for acne (spironolactone, Flutamide etc.,), systemic steroids (Including intra-nasal and in-haled corticosteroids), systemic antibiotics, systemic treatment for acne vulgaris (other than oral retinoids, which require a 6-month washout) or systemic anti-inflammatory agents.
8. Use within 2 weeks prior to baseline (Randomisation) of topical steroids, topical retinoids and topical acne treatments including over-the-counter preparations, topical anti-inflammatory agents, medicated cleansers/shampoo or topical antibiotics.
9. Use within 2 weeks prior to baseline (Randomisation) of abradants, facials, peels containing glycolic or other acids, masks, washes or soaps, containing glycolic acid, salicylic acid, Alpha- or beta-hydroxy acids or other acids, benzoyl peroxide (BPO) or sulfacetamide sodium, non-mild facial cleansers, moisturizers that contained retinol.
10. Subjects who have undergone a facial procedure (e.g., laser peel, microdermabrasion or blue light treatment, etc.) within the past 4 weeks or if it is planned to be performed during the conduct of the study.
11. Concomitant use/planned to use of mega-doses of certain vitamins (such as mega-doses of vitamin D [> 2000 IU/day], vitamin B6 [> 2 mg] or vitamin B12 [> 1 mg/day]), haloperidol, halogens such as iodide and bromide, lithium, hydantoin and phenobarbital.
12. Use of tanning booths or tanning lamps or ultraviolet light within 1 week prior to Baseline and an unwillingness to refrain from use during the study.
13. Subjects with planned unprotected and intense UV exposure during the study (mountain sports, UV radiation, sunbathing, etc.).
14. A significant medical history of or are currently immunocompromised or receiving immunomodulators/ biologics since last 3 months.
15. Subjects with clinically significant vital sign abnormality.
16. Subjects with clinically significant unstable medical disorders, life-threatening disease, or current malignancies.
17. Subjects who engage in activities that involve excessive or prolonged exposure to sunlight or weather extremes, such as wind or cold.
18. History of drug or alcohol abuse within last 6 months.
19. Lived in the same household as currently enrolled subjects.
20. Female subjects who are breast-feeding or planning to become pregnant.
21. Subjects who have been treated with an investigational drug or investigational device within a period of 30 days prior to study enrolment.
22. Subjects with clinically significant abnormal laboratory value which may affect the participation of the subject in the study.
23. Subjects with a clinically significant disease(s) or disorder(s) other than facial acne vulgaris that in the opinion of the Investigator may (i) put the subject at risk because of participation in the study (ii) interfere with the study evaluations or (iii) cause concern regarding subject’s ability to participate in the study.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome
Outcome
TimePoints
Mean percent change from baseline to week 12 in the inflammatory (papules and pustules) lesion count
Mean percent change from baseline to week 12 in the Non-inflammatory (open and closed comedones) lesion count.
Day 1, Week 2, Week 4, Week 8 and Week 12
Secondary Outcome
Outcome
TimePoints
Proportion of subjects with a clinical response of “success†at week 12. (IGA score)
Day 1, Week 2, Week 4, Week 8 and Week 12
The incidence of treatment-emergent adverse events
Day 1, Week 2, Week 4, Week 8 and Week 12
Application site reaction assessments
Week 2, Week 4, Week 8 and Week 12
Target Sample Size
Total Sample Size="981" Sample Size from India="981" 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)?
Brief Summary
A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Three-arm, Parallel Study to Evaluate the Bioequivalence using Clinical Endpoint of Tretinoin Gel microsphere, 0.08% in the Treatment of 981 Subjects with Subjects with Acne Vulgaris. At screening/baseline visit, subjects shall be randomly (Double’blind) assigned in 1:1:1 fashion to one of the 3 treatment groups at visit 2. Statistical comparisons shall be made between test and reference, test and placebo, and reference and placebo. The primary endpoint is test/reference ratio of the mean percent change from baseline to week 12 in the inflammatory (papules and pustules) and non- inflammatory (Comedones) lesion count at Visit 6.The secondary endpoint is the proportion of subjects who are considered a Clinical Success at Week 12. Safety shall be evaluated from reported adverse events and application site reaction assessments.