A bioequivalence study of Tretinoin Gel microsphere 0.08 percent (Amneal pharmaceuticals LLC, USA) as compared to reference medicinal product, Retin-A Micro (Tretinoin) Gel Microsphere 0.08 percent (Valeant pharmaceuticals North America LLC) in patients with acne vulgaris
Scientific Title of Study
A multi-center, double-blind, randomized, three-arm, active and placebo-controlled, parallel group design to evaluate the bioequivalence using clinical endpoint of Tretinoin Gel Microsphere, 0.08 percent (Amneal Pharmaceuticals LLC, USA) with Retin-A Micro (tretinoin) Gel Microsphere 0.08 percent (Valeant Pharmaceuticals North America LLC) in subjects with acne vulgaris.
Trial Acronym
NIL
Secondary IDs if Any
Secondary ID
Identifier
AMN-TRN-001 Version No. 2.0 dated 28/Mar/2024
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Mr Lokesh Chaudhari
Designation
Managing Director– Clinical Operations
Affiliation
Catawba Research India Pvt. Ltd
Address
Catawba Research India Pvt. Ltd.
Address: 303, Antariksh Thakur House, Marol Naka, Makwana Road Andheri- East, Mumbai- 400 059, Maharashtra-India
Mumbai MAHARASHTRA 400059 India
Phone
9833579888
Fax
Email
Lokesh@catawbaresearch.com
Details of Contact Person Scientific Query
Name
Mr Lokesh Chaudhari
Designation
Managing Director– Clinical Operations
Affiliation
Catawba Research India Pvt. Ltd
Address
Catawba Research India Pvt. Ltd.
Address: 303, Antariksh Thakur House, Marol Naka, Makwana Road Andheri- East, Mumbai- 400 059, Maharashtra-India
Mumbai MAHARASHTRA 400059 India
Phone
9833579888
Fax
Email
Lokesh@catawbaresearch.com
Details of Contact Person Public Query
Name
Mr Lokesh Chaudhari
Designation
Managing Director– Clinical Operations
Affiliation
Catawba Research India Pvt. Ltd
Address
Catawba Research India Pvt. Ltd.
Address: 303, Antariksh Thakur House, Marol Naka, Makwana Road Andheri- East, Mumbai- 400 059, Maharashtra-India
Mumbai MAHARASHTRA 400059 India
Phone
9833579888
Fax
Email
Lokesh@catawbaresearch.com
Source of Monetary or Material Support
Amneal Pharmaceuticals LLC.
50 Horseblock Road,
Brookhaven, NY 11719. USA.
Tel. No.: 001-631.952.0214
Fax: 001-631.656.1009
Catawba Research India Private Limited, 401, Metro Avenue, Opposite to WEH Metro Station Andheri East Mumbai, India - 400099
Primary Sponsor
Name
Amneal Pharmaceuticals LLC
Address
50 Horseblock Road, Brookhaven, NY 11719. USA. Tel. No.:
001-631.952.0214 Fax: 001-631.656.1009
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Dr Ilesh Changela
AVP, Global Clinical Affairs,
Amneal Pharmaceuticals Pvt. Ltd.,
Corporate Office, 9th Floor, Iscon Elegance,
Nr. Shapath - 5, Opp. Karnavati Club,
Prahladnagar Crossroads, S.G. Highway,
Ahmedabad – 380015, Gujarat, India
Dr Sharwan Kumar Singhal
DGM, Global Clinical Affairs
Amneal Pharmaceuticals Pvt. Ltd.,
Corporate Office, 9th Floor, Iscon Elegance,
Ahmedabad – 380015, Gujarat, India
Mr Alpesh Viradiya
Sr.Manager, Global Clinical Affairs
Amneal Pharmaceuticals Pvt. Ltd.,
Corporate Office, 9th Floor, Iscon Elegance,
Ahmedabad – 380015, Gujarat, India
Clinical Research Department,
4th and 5th floor, Starplus Complex Lam Road Near Muktidham Temple, Opposite to NMC Divisional office, Nasik Road, Nasik – 422101, Maharashtra,India Nashik MAHARASHTRA
9595789893
Drtruptis232@gmail.com
Dr Nisha Parikh
CIMETs Inamdar Multispeciality Hospital
Clinical Research Room- Admin Building Sr No. 15 Behind KPCT mall, Fatima Nagar, Pune – 411040 Maharashtra India Pune MAHARASHTRA
9673834553
drnishaparikh@gmail.com
Dr Sharmila Patil
D. Y. Patil Medical Hospital and Research Centre
Clinical research Room on 5th Floor, Sector 5, Nerul, Navi Mumbai – 400706, Maharashtra, India Mumbai MAHARASHTRA
9821350217
drsharmilapatil@gmail.com
Dr Kavita Nimje
Deoyani Multispecialty Hospital
Plot no. 121, Zone no. 04, Dahanukar Colony, Kothrud, Pune – 411038, Maharashtra, India Pune MAHARASHTRA
9664777550
drkavitanimje.deoyani@gmail.com
Dr Bhushan Telhure
Dr Vasantrao Pawar Medical College, Hospital and Research center
Dr Vasant Rao Pawar Medical College, Hospital and Research center Mumbai- Clinical research Room 1st Floor Room no. I-239 & I-240 Agra National Hwy, Vasantdada Nagar, Adgaon, Nashik- 422003, Maharashtra, India Nagpur MAHARASHTRA
9664777550
bhushan.telhure@gmail.com
Dr Panna Shah
Dr. Jivraj Mehta Smarak Health Foundation Bakeri Medical Research Centre
Dr. Jivraj Mehta Smarak Health Foundation Bakeri Medical Research Center, Clinical Research Room- Basement Mehta Marg, Ahmedabad- 380007 Gujarat, India Ahmadabad GUJARAT
Clinical Research department Floor no 3 beside ICU Ajgaonkar plot, Western Express Highway, Jogeshwari East Mumbai – 400060 Maharashtra India Mumbai MAHARASHTRA
8976101326
drgeoffreyvaz1@yahoo.com
Dr Saurabh Kapadia
Hitech Multispeciality Hospital
Clinical research Room- Basement 3D, Plot no. 1180, GH road, Near GH 11/2 bus stand, Gandhinagar – 381003 Gujarat, India Gandhinagar GUJARAT
9824261031
drsaurabhkapadiacr@gmail.com
Dr Prashant Palwade
Ishwar Institute of Healthcare
Ishwar Heights, 1st floor, plot no.7, gut no. 6/1, beside Punjabi Bhavan, Padegaon, Aurangabad – 431002, Maharashtra, India Aurangabad MAHARASHTRA
9323707031
ishwarhealthcare@gmail.com
DrAmit Malhotra
Jaipur National University Institute for Mediacal Science &Research Centre
Jaipur National University Institute for Mediacal Science &Research Centre,Near new RTO office Jagatpura,Jaipur,Rajasthan 302017,India. Jaipur RAJASTHAN
9027316046
amitmalhotra.jnu@gmail.com
Dr Kethireddi S Divya
King George Hospital, Department of Dermatology
King George Hospital,
Maharanipeta, Visakhapatnam-530002, Andhra Pradesh, India Visakhapatnam ANDHRA PRADESH
7780156216
drsusmithadivyaresearch@gmail.com
Dr Monika Gowda
Medstar Speciality Hospital
2nd floor, Research department No. 641/17/1/3 kodhigehalli main road Sahakarnagar, Bangalore – 560092 Karnataka, India Bangalore KARNATAKA
9538880387
dr.monikagowda.medstar@gmail.com
Dr Mamta Patil
Ojas Multispeciality Hospital
Clinical Research Room-Ground Floor Bhondave Chowk, Ravet, Pune-412101 Maharashtra, India. Pune MAHARASHTRA
7738927929
drmamtapatil89@gmail.com
Dr Manjunath Shenoy
Omega Hospital (P) Ltd
Clinical research Room 4th Floor Mahaveer Circle, Kankanady, Mangalore – 575002, Karnataka India Dakshina Kannada KARNATAKA
9845009976
manjunathshenoy.dermatology@gmail.com
Dr Sudheer N
Osmania General Hospital
Department of DVL, 1st floor OP block.
Osmania General Hospital, Afzalgunj, Hyderabad – 500012, Telangana, India
Hyderabad TELANGANA
9948111264
neelamsudheer8@gmail.com
Dr Adarsh Gowda
Santosh Hospital
Clinical Research Room no.310 3rd Floor. 6/1, Promenade Road, Behind Coles Park, Bangaluru, 560005. Karnataka, India Bangalore KARNATAKA
9686100333
adarshgowda@hotmail.com
Dr Shyamal Balki
Shree Hospital and Critical Care Centre
Shree Hospital Critical Care Centre , Clinical Research Room- Basement 799 Om Nagar Opposite Tejashree Building Sakkardara Square Nagpur, 440009 Maharashtra India Nagpur MAHARASHTRA
8600998134
drshyamalb@gmail.com
Dr Nikhil Kajale
Signus Hospital
5th Floor, Atlanta Shoppers, Pathardi Phata, Nashik – 422010 Maharashtra, India Nagpur MAHARASHTRA
Ethics Committee of Ishwar Institute of Health Care,
Approved
Ethics Committee of Trauma Care Hospital
Approved
Hi-Tech Ethics Committee
Approved
IEC, Dr. Vasantrao Pawar Medical College, Nashik
Approved
IEC, King George Hosiptal
Approved
IEC, Sardarmal Khandaka Memorial Hospital
Approved
Independent Ethics Committee
Approved
Institutional Ethics Committee
Approved
Institutional Ethics Committee
Approved
Institutional Ethics Committee Dr. Jivraj Mehta Smarak Health Foundation
Approved
Institutional Ethics Committee, Assured Care Plus Hospital
Approved
Jaipur National University Institute for Mediacal Science & Research Centre
Approved
Medstar speciality hospital Ethics Committee
Approved
Ojas Multispeciality Hospital Ethics Committee
Approved
Omega Ethical Committee
Approved
Santosh Hospital, Institutional Ethics Committee
Approved
Shree Hospital Ethics Committee
Approved
Signus Hospital Ethics Committee
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: L99||Other disorders of skin and subcutaneous tissue in diseases classified elsewhere,
Intervention / Comparator Agent
Type
Name
Details
Comparator Agent
Placebo
Amneal Pharmaceuticals LLC, USA
Dosage: Vehicle Placebo gel applied once daily for 12 weeks
Frequency: application once daily at bedtime
Route of Administration: Topical
Duration of Therapy: 12 weeks
Comparator Agent
RETIN-A MICRO® Gel
Comparator RETIN-A MICRO® (tretinoin) Gel microsphere 0.08% of Valeant
Pharmaceuticals North America LLC, Bridgewater, NJ 08807 USA,
Dosage: 0.08% of gel applied once daily for 12 weeks
Frequency: application once daily at bedtime
Route of Administration: Topical
Duration of Therapy: 12 weeks
Intervention
Tretinoin Gel
Tretinoin Gel microsphere, 0.08% of Amneal Pharmaceuticals LLC, USA
Dosage: 0.08% of gel applied once daily for 12 weeks
Frequency: application once daily at bedtime
Route of Administration: Topical
Duration of Therapy: 12 weeks
Inclusion Criteria
Age From
12.00 Year(s)
Age To
40.00 Year(s)
Gender
Both
Details
1.Healthy males or non-pregnant, non-lactating females aged ≥ 12 and ≤ 40 years with a clinical diagnosis of acne vulgaris.
2.Subjects aged 18 years or older (up to the age of 40 years) must have provided IRB/IEC approved written informed consent. Subjects aged 12 to 17 years inclusive, must provide IRB/IEC approved written assent; this written assent must be accompanied by an IRB/IEC approved written informed consent from the subject’s legally acceptable representative (i.e., parent or guardian).
3.Subjects must have ≥ 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), at baseline on the face.
Note: For the purposes of study treatment and evaluation, these lesions should be limited to the facial treatment area. All facial lesions will be counted, including those on the nose.1 Counts of nodules and cysts will be reported separately and not included in the inflammatory or non-inflammatory lesion counts. Nodulocystic lesions will not be included in the inflammatory lesion count
4.Subjects must have a definite clinical diagnosis of acne vulgaris
severity grade 2, 3, or 4 as per the Investigator’s Global Assessment
(IGA)
5.Subjects must be willing to refrain from using all other topical acne medications or antibiotics for acne vulgaris during the 12-week treatment period, other than the investigational product.
6.Female subjects of childbearing potential (excluding women who are premenarchal, surgically sterilized (by hysterectomy) or postmenopausal for at least 1 year), in addition to having a negative urine pregnancy test, must be willing to use an acceptable form of birth control during the study from the day of the first dose administration to 30 days after the last administration of study drug.
a.For the purpose of this study the following are considered acceptable methods of birth control: oral or injectable contraceptives, contraceptive patches, Depo-Provera® (stabilized for at least 3 months), NuvaRing® (vaginal contraceptive), Implanon™ (contraceptive implant), double barrier methods (e.g., condom and spermicide), IUD, tubal ligation, Essure or abstinence with a 2nd acceptable method of birth control should the subject become sexually active.
b.Subjects on hormonal contraception must be stabilized on the same type for at least three months prior to enrollment in the study and must not change the method during the study
c. A sterile sexual partner is NOT considered an adequate form of birth control.
Full hysterectomy or bilateral oophorectomy considered
surgically sterile. Tubal ligation is not considered equivalent to female sterilization.
7.All male subjects must agree to use acceptable methods of birth control with their partners, from the day of the first dose administration to 30 days after the last dose administration of study drug. Abstinence is an acceptable method of birth control. Female partners should use an acceptable method of birth control as described in criteria 6
8.Subjects must be willing and able to understand and comply with the protocol requirements, including attendance at the required study visits.
9.Subjects must be in good health and free from any clinically significant disease, including but not limited to, conditions that may interfere with the evaluation of acne vulgaris. Such conditions include but are not limited to the following: auto immune disease;
rosacea; seborrheic dermatitis; perioral dermatitis; corticosteroid induced acne; carcinoid syndrome; mastocytosis; acneiform eruptions caused by make-up, medication, facial psoriasis, and facial eczema.
10.Subjects who use make-up must have used the same brands/types of make-up for a minimum of 14 days prior to study entry and must agree not to change make-up brand/type or frequency of use throughout the study
ExclusionCriteria
Details
1.Female subjects who are pregnant, nursing or planning to become pregnant during study.
2.Subjects with a history of hypersensitivity or allergy to tretinoin, retinoids, or any of the study medication ingredients.
3.Subjects with 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, acneiform eruptions caused by medications, steroid acne, steroid folliculitis, or bacterial folliculitis.
4.Subjects with excessive facial hair (e.g., beards,sideburns,moustaches,etc.)that would interfere with diagnosis or assessment of acne vulgaris.
5.Subjects with a baseline irritation score of 3 is equal to severe (marked, intense).
6.Subjects who have used within 6 months prior to baseline or use during the study of oral retinoids (e.g.,Accutane®) or therapeutic vitamin A supplements of greater than 10,000 units per day (multivitamins are allowed).
7.Concomitant use planned to use of mega-doses of certain vitamins (such as mega-doses of vitamin D greater than 2000 IU per day, vitamin B6 greater than 2 mg or vitamin B12 greater than 1 mg per day), haloperidol, halogens such as iodide and bromide, lithium, hydantoin and phenobarbital.
8.Subjects with planned unprotected and intense UV exposure during the study (mountain sports, UV radiation, sunbathing, etc.).
9.Use of anti-pruritic, including antihistamines, within 24 hours of baseline visit.
10.Subjects who have had laser therapy, electrodessication, and phototherapy (e.g., ClearLight®) to the facial area within 6 months prior to study entry.
11.Subjects who have received radiation therapy and/or anti-neoplastic agents within 3 months prior to baseline.
12.Subjects who have used estrogens or oral contraceptives for less than 3 months prior to baseline.
13.Subjects who have used any of the following procedures on the face within 1 month prior to baseline or use during the study:
a. cryodestruction or chemodestruction,
b. dermabrasion,
c. photodynamic therapy,
d. acne surgery,
e. intralesional steroids, or
f. X-ray therapy.
14.Subjects who have used any of the following treatments within 1
month prior to baseline or during the study:
a. spironolactone
b. systemic steroids,
c. systemic antibiotics,
d. systemic treatment for acne vulgaris, or
e. systemic anti-inflammatory agents. If subject uses a
systemic anti-inflammatory product during the study, the
Principal Investigator (PI) will judge if this protocol
violation is clinically significant,
f. have taken any drugs that lower the immune system.
15.Subjects who have used any of the following treatments within 2 weeks prior to baseline or during the study:
a. topical steroids,
b. topical retinoids,
c. topical acne treatments including over-the-counter preparations
d. topical anti-inflammatory agents, or
e. topical antibiotics.
16.Subjects who have done wax depilation of the face within 14 days prior to baseline.
17.Subjects who have had cosmetic procedures (e.g., facials) which may affect the efficacy and safety profile of the investigational product within 14 days prior to study entry.
18.Subjects who have on-going malignancies requiring systemic treatment or who have any malignancy of the skin of the facial area.
19.Subjects with eczematous skin.
20. Subjects who have unstable medical disorders that are clinically significant or have life-threatening diseases, or other medical condition that, in the investigator’s opinion, would place the study subject at undue risk by participation or could jeopardize the integrity of the study evaluations.
21.Subjects who engage in activities that involve excessive or prolonged exposure to sunlight or weather extremes, such as wind or cold.
22.Subjects who consume excessive amounts of alcohol (greater than two drinks per day) or use drugs of abuse (including, but not limited to, cannabinoids, cocaine, and barbiturates).
23.Subjects who have participated in an investigational drug study (i.e., subjects treated with an investigational drug) within 30 days prior to baseline. Subjects participating in non-treatment studies such as observational studies or registry studies can be considered for inclusion.
24.Subjects who have been previously enrolled in this study.
25.Subjects who are members of the same household with subjects participating or previously enrolled in this 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
1 Mean percent change from baseline to week 12 in the inflammatory (papules and pustules) lesion count.
2 Mean percent change from baseline to week 12 in the Noninflammatory (open and closed comedones) lesion count..
Baseline to 12-Week Treatment period
Secondary Outcome
Outcome
TimePoints
1 Proportion of subjects with a clinical response of IGA score at week 12 compared to baseline.
2 The superiority of the test & reference (active) treatments over placebo (vehicle).
3 The incidence of treatment-emergent adverse events (TEAEs).
4 Application site reaction assessments.
Baseline to 12-Week treatment period
Target Sample Size
Total Sample Size="1071" Sample Size from India="1071" Final Enrollment numbers achieved (Total)= "1071" Final Enrollment numbers achieved (India)="1071"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
AMNEAL PHARMACEUTICALS LLC, USA. has developed a generic product (TRETINOIN GEL MICROSPHERE, 0.08%) of RETIN-A MICRO® (TRETINOIN) GEL MICROSPHERE 0.08%. AMNEAL PHARMACEUTICALS LLC, USA wants to conduct the study to assess the BIOEQUIVALENCE of test product in comparison to the reference product using clinical endpoint evaluation & superiority of test and Reference product over Placebo product in subjects with ACNE VULGARIS in line with the applicable USFDA’s Guidance.
A MULTI-CENTER, DOUBLE-BLIND, RANDOMIZED, THREE ARM, ACTIVE AND PLACEBO-CONTROLLED, PARALLEL GROUP DESIGN TO EVALUATE THE BIOEQUIVALENCE USING CLINICAL ENDPOINT OF TRETINOIN GEL MICROSPHERE, 0.08% (AMNEAL PHARMACEUTICALS LLC, USA) WITH RETIN-A MICRO® (TRETINOIN) GEL MICROSPHERE 0.08% (VALEANT PHARMACEUTICALS NORTH AMERICA LLC) IN SUBJECTS WITH ACNE VULGARIS.
Primary Objective:
-To evaluate bioequivalence of test Tretinoin Gel microsphere, 0.08% (Amneal Pharmaceuticals LLC) with reference Retin-A Micro® (tretinoin) Gel microsphere 0.08% (Valeant Pharmaceuticals North America LLC) in subjects with Acne Vulgaris. To demonstrate the superiority of the test and reference (active) treatments over placebo in the treatment of subjects with Acne Vulgaris.
Secondary Objective:
-To assess the safety and tolerability of study treatments in subjects with Acne Vulgaris.