Combination Treatment of Winlevi With Duac Gel in Patients With Acne Vulgaris
Phase: PHASE4
Conditions: Acne Vulgaris
Sponsor: Sun Pharmaceutical Industries Limited

Official title: Combination Treatment of Winlevi with Duac Gel in Patients With Acne Vulgaris. 
Document: Study Protocol 
NCT number: NCT06336629 
Document date: 06 Feb 2023 

PILOT STUDY PROTOCOL 
 
 
 
 
 
Protocol Title  
 
Combination treatment of Winlevi with Duac gel in 
patients with acne vulgaris 
 
 
 
 
Protocol Number 
 
WIN2023 
 
 
 
 
 
Protocol Date 
 
February 6, 2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 2 of 14 
 
 
PROTOCOL SIGNATURE PAGE 
 
 
 
The signature below constitutes the approval of this protocol and the supplements, and provides the 
necessary assurances that this trial will be conducted according to all stipulations of the protocol, 
including all statements regarding confidentiality, and according to local legal and regulatory 
requirements and ICH-GCP guidelines. 
 
 
 
 
 
 
Investigator 
      

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 3 of 14 
 
 
1 
GENERAL INFORMATION 
1.1 
Introduction 
 
Acne vulgaris is the most common skin disease in patients with skin of color and second most 
common in Caucasian population1.  The global prevalence is thought to be as high as 60-80% in 
individuals 12-25 years of age1,2.  However, it is not limited to only teenagers but also to adults, 
especially adult females3.  The pathogenesis of acne is multifactorial.  Genetics may also play a 
role.  The treatment pathway should be directed to different pathogenic factors including, excessive 
sebum production, hyper keratinization, P. acnes, and inflammation4,5,6,7,8.  
 
Winlevi is the first topical anti androgen and sebum inhibitor approved for acne vulgaris.9 However, 
we do not have any clinical experience with Winlevi in combination treatment for acne . Acne 
vulgaris is a multifactorial disease and topical retinoids and Benzoyl peroxide and topical 
clindamycin products have been mainstay treatments for acne in our clinical practices. 
 
Therefore ,it  is reasonable to study Winlevi with Duac gel in  combination to emulate real life 
practice. 
 
 
References: 
1. Ghodsi SZ, Orawa, H, Zouboulis, CC: Prevalence, severity, and severity of risk factors in 
acne in high school pupils; a community based study. J Invest Dermatol 2009;129:2136-
2141 
2. Plewig G, Kligman AM: Acne and rosacea, ed 3. Berlin Springer, 2000. 
3. Perkins AC, Maglione J, Hillebrand GG, Miyamoto K, Kimball AB: Acne vulgaris in 
women, prevalence across the life span. J Womens Health (Larchmt) 2012;21:223-230 
4. Williams C, Layton AM: Persistent acne in women: implications for the patient and for 
therapy. Am J Clin Dermatol 2006;7:218-290 
5. Jeremy AH, Holland DB, Roberts SG, Thompson KF, Cunliffe WJ: Inflammatory events 
are involved in acne lesion initiation. J invest Dermatol 2003;121:20-27 
6. Nagy I, Pivarcsi A, Koreck A, Szell M, Urban E, Kemeny L: Distinct strains of Propioni-
bacterium acnes induce selective human -defensin-2 and interleukin-8 expression in 
human keratinocytes through toll-like receptors. J Invest Dermatol 2005;124:931-938 
7. Holland C, Mak TN, Zimny-Arndt U, Schmid M, Meyer TF, Jungblut PR, Bruggemann 
H: Proteomic indentification of secreted proteins of Propionibacterium acnes. BMC 
microbiol 2010;10:230 
8. Lomholt HB, Kilian M: Population genetic analysis of Propionibacterium acnes identifies 
a subpopulation and epidemic clones associated with acne. PloS One 2010;5:e12277 
9. Winlevi packge insert 
 
 
 
 

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 4 of 14 
 
 
1.2 
Study Population 
Ten (10) subjects with moderate to severe facial acne vulgaris.   
 
2 
STUDY OBJECTIVES 
The objectives of this study are to observe the efficacy and safety of combination treatment of Winlevi 
and Duac gel as a treatment modality for moderate to severe acne.  
 
Primary objective: Percent of subjects who are clear or almost clear on IGA scale at week 16. 
 
Secondary objectives: 1. Percent of total lesion reduction at week 12 compared to baseline 
 
 
 
2. Percent of inflammatory lesion reduction at week 16 compared to baseline 
 
 
 
3. Percent of non-inflammatory lesion reduction at week 16 compared to  
 
 
 
baseline. 
 
 
 
4. Tolerability measures such as, erythema, scaling, dryness, oiliness,  
 
 
 
burning/stinging, and pruritus. 
 
3 
STUDY DESIGN 
This is a two-center, open-label pilot study. All study subjects will receive both Winlevi and Duac gel 
gel at baseline.  The duration of the study is 16 weeks and consists of a Screening, Baseline Visit, 
and five (5) Follow-up Visits at Weeks 4, 8, 12 and 16. The treatment period is 12 weeks and 4 
weeks of safety follow up totaling to 16 weeks. 
 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Inclusion Criteria 
i. 
Outpatient, male or female subjects of any race, and at least 12 years of age or older. 
Female subjects of childbearing potential must have a negative urine pregnancy test result 
at Baseline (test must have a sensitivity of at least 25mIU/ml for human chorionic 
gonadotropin) and practice a reliable method of contraception throughout the study: 
 
A female is considered of childbearing potential unless she is: 
- postmenopausal for at least 12 months prior to study drug administration; 
- without a uterus and/or both ovaries; or 
- has been surgically sterile for at least 6 months prior to study drug administration.  
Reliable methods of contraception are: 
- hormonal methods or intrauterine device in use > 90 days prior to study drug administration; 
- barrier methods plus spermicide in use at least 14 days prior to study drug administration; or 
- vasectomized partner (vasectomy must be performed 3 months prior to first study drug 
administration or in the alternative a zero sperm count will suffice)  
 
[Exception:  Female subjects of childbearing potential who are not sexually active will not be required to practice a 
reliable method of contraception. These subjects may be enrolled at the Investigator’s discretion if they are counseled 
to remain sexually inactive during the study and understand the possible risks in getting pregnant during the study.] 
ii. 
Facial acne IGA score of 3 or 4. 
iii. 
Able to understand the requirements of the study and sign Informed Consent/HIPAA 
Authorization forms. Subjects under the legal age of consent in the state where the study is 
conducted must also have the written, informed consent of a parent or legal guardian.   

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 5 of 14 
 
 
4.2 
Exclusion Criteria 
i. 
Female subjects who are pregnant (positive urine pregnancy test), breast-feeding, or who 
are of childbearing potential and not practicing a reliable method of birth control.  
ii. 
Allergy or sensitivity to any component of the test medications (Section 5.2). 
iii. 
Subjects who have not complied with the proper wash-out periods for prohibited medications 
(Supplement I). 
iv. 
Medical condition that, in the opinion of the Investigator, contraindicates the subject’s 
participation in the clinical study. 
v. 
Skin disease/disorder that might interfere with the diagnosis or evaluation of acne vulgaris  
vi. 
Evidence of recent alcohol or drug abuse. 
vii. 
History of poor cooperation, non-compliance with medical treatment, or unreliability. 
viii. 
Exposure to an investigational drug study within 30 days of the Baseline Visit. 
ix. 
 Patients who have demonstrated hypersensitivity (e.g., anaphylaxis) to clindamycin, benzoyl 
peroxide, any components of the formulation, or lincomycin. (4)  Patients with a history of 
regional enteritis, ulcerative colitis, or antibiotic-associated colitis (including 
pseudomembranous colitis) 
4.3 
Withdrawal of Subjects 
It is the right and duty of the Investigator to discontinue the study participation of a subject when the 
subject's health or well-being is threatened by continuation in the study. Such subjects should be 
withdrawn from the study. 
 
The following are circumstances that would result in the subject's discontinuation from the study: 
 
 
the subject experiences a serious adverse event rendering them unable to continue study participation; 
 
the subject is unable to physically or mentally tolerate the use of the test medication; 
 
an exclusion criterion becomes apparent at any time during the study; or 
 
the subject voluntarily withdraws. 
 
In the event of premature discontinuation from the study, the Investigator should determine the 
primary reason for discontinuation.  A subject who is withdrawn from the study prior to initiation of 
treatment may be replaced. 
 
 

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 7 of 14 
 
 
 
Subject Demographics/Medical History 
 
Weight/Height 
 
Vital Signs 
 
Concomitant Medication/Treatment 
 
Assessments 
-
Acne IGA
- 
Lesion Counts 
- 
Tolerability 
Inclusion/Exclusion Criteria
 
Dispense Study medication 
 
DLQI 
 
Instruct regarding application procedures 
 
5.1.3 Visits 2, 3, 4  (Weeks 4, 8, 12 ± 3 days) 
 
Concomitant Medication/Treatment 
 
Urine Pregnancy Test (if applicable) 
 
Adverse Events 
 
Vital Signs 
 
Collect Study Medication 
 
DLQI 
 
Assessments 
- 
Acne IGA 
- 
Lesion Counts 
- 
Tolerability 
 
 
5.1.4 Visit 5 (Week 16; ± 5 days) 
 
Urine Pregnancy Test (if applicable) 
 
Concomitant Medication/Treatment 
 
Adverse Events 
 
Vital Signs 
 
Weight 
 
DLQI 
 
Assessments 
- 
Acne IGA 
- 
Lesion Counts 
- 
Tolerability 
 
5.2 
Study Treatment 
5.2.1 Details of Study Treatment 
Apply a thin layer of DUAC Gel to the face once daily, in the evening. (2)  Not for oral, ophthalmic, 
or intravaginal use. (2) 
 

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 8 of 14 
 
 
WINLEVI cream 1% is supplied in an epoxy-lined aluminum blind-end tube with a polypropylene 
cap closure: NDC 47335-994-36 60-gram tube
 
 
 
 5.2.2    Storage and Handling  
 
DUAC (clindamycin phosphate and benzoyl peroxide) Gel, 1.2%/5% is a fixed combination product 
with two active ingredients in a white to slightly yellow, opaque, aqueous gel formulation. 
Clindamycin phosphate is a water soluble ester of the semi-synthetic antibiotic produced by a 7(S)-
chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin. Clindamycin 
phosphate is C18H34ClN2O8PS. The structural formula for clindamycin phosphate is represented 
below: 5 Reference ID: 3428618 CH3 Cl N H H H N CH3 H H OH 3C O O H OH SC H 3 O OH P 
HO O Clindamycin phosphate has a molecular weight of 504.97 and its chemical name is methyl 7-
chloro-6,7,8-trideoxy-6-(1-methyl-trans-4-propyl-L-2-pyrrolidinecarboxamido)-1-thioL-threo- -D-
galacto-octopyranoside 2-(dihydrogen phosphate). Benzoyl peroxide is C14H10O4. It has the 
following structural formula: Benzoyl peroxide has a molecular weight of 242.23. Each gram of 
DUAC Gel contains 10 mg (1%) clindamycin, as clindamycin phosphate, and 50 mg (5%) benzoyl 
peroxide in a base consisting of carbomer homopolymer (type C), dimethicone, disodium lauryl 
sulfosuccinate, edetate disodium, glycerin, methylparaben, poloxamer 182, purified water, silicon 
dioxide, and sodium hydroxide. 
 
 
 
 
WINLEVI (clascoterone) cream contains clascoterone, an androgen receptor inhibitor, in a cream 
base for topical dermatologic use. WINLEVI cream is a white to almost white cream. Chemically, 
clascoterone is cortexolone-
ost white powder, 
practically insoluble in water. The compound has the empirical formula C24H34O5 and molecular 
weight of 402.5 g/mol. The structural formula is shown below. Each gram of WINLEVI cream 1% 
contains 10 mg of clascoterone in a cream base of cetyl alcohol, citric acid monohydrate, edetate 
disodium, mineral oil, mono- and di-glycerides, polysorbate 80, propylene glycol, purified water, and 
vitamin E. 
 
 
5.2.3 Dispensation and Dosage Schedule 
Apply a thin layer of DUAC Gel to the face once daily, in the evening. (2)  Not for oral, 
ophthalmic, or intravaginal use. (2) 
 
 
Winlevi Cream• Apply a thin layer (approximately 1 gram) to affected area twice daily (morning and 
evening). Avoid contact with eyes, mouth, and mucous membranes. (2) • Not for ophthalmic, oral or 
vaginal use. (2) 
 
 
 

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 9 of 14 
 
 
5.2.4 Treatment Assignment 
The study medication will be administered only to eligible subjects as defined by the Study Protocol. 
 All subjects who have signed an ICF will receive a 2-digit subject number, starting at 01.  This 
subject number will be used to identify the subject throughout the study.  Subjects withdrawn from 
the study will retain their subject number. New subjects will be allotted a new subject number. 
 
5.2.5 Blinding, Packaging, and Labeling 
Commercially available and labeled medications will be used.  Medications will be dispensed in an 
open-label fashion. 
 
5.2.6 Supplies and Accountability 
The Investigator or pharmacist will inventory and acknowledge receipt of all shipments of study 
medication.  All study medication must be kept in a locked area with access restricted to designated 
study personnel.  The study medication must be stored in accordance with the instructions provided 
with the shipment.  The Investigator or pharmacist will also keep accurate records of the quantities 
of study medication dispensed and returned by each subject. 
 
5.2.7 Treatment Compliance 
Subject compliance to study treatment regimen will be assessed at each visit; study personnel will 
ask each subject whether they missed any applications of study medication since the previous visit. 
 
5.3 
Concomitant Medication/Treatment 
Please see Supplement I for a listing of prohibited medications.  Necessary therapies that will not 
interfere with the response to treatment may be provided at the discretion of the Investigator.  The 
use of any concurrent medication, prescription or over-the-counter drug, is to be recorded in the 
CRF along with the reason the medication was taken. 
 
5.4       Summary of known and potential risks 
5.5       Summary of Benefits 
There may be certain direct benefits derived from participating in this study. Such benefits include 
temporary, partial or complete, clearance of your acne lesions; however, it is possible that you 
receive no benefit. The results of this study may be useful in the development of a new therapy for 
others with similar conditions to yours. 

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 12 of 14 
 
 
 
7.2.3 Follow-up and Final Reports 
Subjects who have had a serious adverse event must be followed clinically until all parameters, 
including laboratory values (if applicable), have either returned to normal or are otherwise explained. 
 
If death was the outcome of the event on the initial SAE Report, a Follow-up/Final Report, including 
autopsy report, when performed, must be completed. 
 
8 
STATISTICS 
8.1 
Sample Size Justification 
A total of 20 subjects will be entered into the study.  This is a pilot study and a formal justification for 
the sample size is not provided.  The data from this study will provide important data for determining 
any trends regarding the safety and efficacy of study medication. 
 
8.2 
Analyses 
Statistical analyses will be conducted on an intent-to-treat basis (i.e., all enrolled subjects will be 
included in the analyses).  All statistical tests will be two-sided and interpreted at a 5% significance 
level.  Descriptive statistics (i.e., mean, standard deviation, etc.) will be provided for all continuous 
variables and frequencies for all categorical variables collected in this study.  These will be 
presented by treatment group.  Summary tables will be used to present patient population 
characteristics at Baseline; data from the study questionnaires will be included.  The incidence and 
severity of adverse and/or unexpected events will be tabulated and a complete listing of all reports 
of adverse and/or unexpected events will be presented. 
 
8.3 
Interim Analyses 
No interim analyses will be conducted. 
 
9 
RESPONSIBILITIES OF THE INVESTIGATOR 
9.1 
Good Clinical Practice 
Investigators must adhere to the procedures outlined in this Study Protocol.  The procedures set out 
in this study protocol, pertaining to the conduct, evaluation, and documentation of this study, are 
designed to ensure that the Investigators and CRO abide by GCP as described in the ICH 
Guidelines Topic E6: “Guideline for Good Clinical Practice.”  Compliance with these regulations also 
constitutes compliance with the ethical principles described in the current revision of the Declaration 
of Helsinki.  The study will also be carried out in keeping with local legal and regulatory 
requirements. 
 
9.2 
Ethics 
The appropriate IRB must review the Study Protocol and the Informed Consent Form prior to 
initiating the study.  Any significant modifications to the IRB-approved protocol or informed consent 
must be made in consultation with the IRB. 
 
9.3 
Confidentiality of Subjects 
Any information that identifies subjects with respect to this research study will be kept confidential.  
However, records identifying the subject may be inspected by representatives of the IRB, the 
Clinical Research Organization (or its designate) if applicable, and/or the FDA.  Subjects’ identity will 
remain strictly confidential during all record reviews, as well as in any publication that may result 

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 14 of 14 
 
 
OTC acne medications or bleaching agents 
1Week washout prior to V1 
Oral Antibiotics for acne
4Weeks washout prior to V1 
Oral Retinoids 
24Weeks washout prior to V1 
Cryotherapy, chemical peels, microdermabrasion
2Weeks washout prior to V1 
Laser Resurfacing and dermabrasion 
24Weeks washout prior to V1 
Investigational Drugs 
4Weeks washout prior to V1 

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 15 of 14 
 
 
Dermatology Life Quality Index (DLQI)
 
The aim of this questionnaire is to measure how much your skin problem has affected your life 
OVER THE LAST WEEK.  Please circle one response for each question below. 
 
1. Over the last week, how itchy, sore, painful or stinging has your skin been? 
a. Very Much 
b. A Lot 
c. A Little 
d. Not at All 
 
2. Over the last week, how embarrassed or self-conscious have you been because of your 
skin? 
a. Very Much 
b. A Lot 
c. A Little 
d. Not at All 
 
3. Over the last week, how much has your skin interfered with you going shopping or 
looking after your home or garden? 
a. Very Much 
b. A Lot 
c. A Little 
d. Not at All 
e. Not Relevant 
 
4. Over the last week, how much has your skin influenced the clothes you wear? 
a. Very Much 
b. A Lot 
c. A Little 
d. Not at All 
e. Not Relevant 
 
5. Over the last week, how much has your skin affected any social or leisure activities? 
a. Very Much 
b. A Lot 
c. A Little 
d. Not at All 
e. Not Relevant 
 
 
6. Over the last week, how much has your skin made it difficult for you to do any sport? 
a. Very Much 
b. A Lot 
c. A Little 

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 16 of 14 
 
 
d. Not at All
e. Not Relevant
7. Over the last week, has your skin prevented you from working or studying?
a. Yes 
b. No 
c. Not Relevant 
 
If “No”, over the last week how much has your skin been a problem at work 
or studying? 
a. A Lot 
b. A Little 
c. Not at All 
 
8. Over the last week, how much has your skin created problems with your partner or any 
of your close friends or relatives? 
a. Very Much 
b. A Lot 
c. A Little 
d. Not at All 
e. Not Relevant 
 
9. Over the last week, how much has your skin caused any sexual difficulties? 
a. Very Much 
b. A Lot 
c. A Little 
d. Not at All 
e. Not Relevant 
 
10. Over the last week, how much of a problem has the treatment of your skin been, for 
example by making your home messy, or by taking up time? 
a. Very Much 
b. A Lot 
c. A Little 
d. Not at All 
e. Not Relevant 
 
 

WIN2023 (v.06feb2023) 
 
 
        
                           
 
 
         Page 17 of 14