Clindamycin Phosphate Topical Lotion Eq. 1% Base among subjects with Acne.
Scientific Title of Study
A multi-center, double-blind, randomized, parallel group, active and placebo-controlled in vivo
clinical endpoint based bioequivalence study of Clindamycin Phosphate Topical Lotion Eq. 1%
Base among subjects with Acne Vulgaris.
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
BE/19/070 Version No.: 00 Dated: 24/04/19
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)
Name
Dr Krunal Chauhan
Designation
Medical Monitor
Affiliation
Raptim Research Ltd.
Address
Clinical Pharmacology Unit (A-226), Bioanalytical and Biostatistical Unit (A-242) T.T.C., Industrial Area, Mahape M.I.D.C., Navi Mumbai. Thane.
Mumbai (Suburban) MAHARASHTRA 400701 India
Phone
02227781889
Fax
02227781884
Email
krunal.chauhan@raptimresearch.com
Details of Contact Person Scientific Query
Name
Dr Amrut Jadhav
Designation
Medical Monitor
Affiliation
Raptim Research Ltd.
Address
Clinical Pharmacology Unit (A-226), Bioanalytical and Biostatistical Unit (A-242) T.T.C., Industrial Area, Mahape M.I.D.C., Navi Mumbai. Thane.
Aadhar Health Institute ,OPD No 15 , Ground Floor , Tosham Road , Near South Bypass Crossing
Hisar HARYANA
8390873920
drpreetisaharanjakhar@gmail.com
DrBelaJShah
B.J Medical College & Civil HospitalÂ
Department of Dermatology,
First floor, OPD
S.T.D., AIDS & Leprosy,
B.J. Medical College & Civil Hospital, Asarwa,
Ahmedabad-380016,
Ahmadabad GUJARAT
9898059289
shah.drbela@gmail.com
Dr Panna Shah
Dr. Jivraj Mehta Smarak Health Foundation
Dr Jivraj Mehta Smarak Health Foundation and Bakeri Medical Research Centre, Basement,
Ground floor, Dermatology department,
Ratubhai Adani Arogyadham Dr Jivraj Mehta Marg,
Ahmedabad–380007, Ahmadabad GUJARAT
9428608796
drshahpanna@gmail.com
Dr V Revati
Government Medical College and Government General Hospital
Government Medical College and Government General Hospital (old-RIMS), Research Wing, 2nd Floor, Beside FM Ward Srikakulam ANDHRA PRADESH
9908066043
drrevathivggh@gmail.com
Dr Bhagyashree Supekar
Government Medical College and HospitalÂ
Government Medical college & Hospital, Department of Skin & V.D. Government Medical college & Hospital, Medical College Square Road Nagpur MAHARASHTRA
9421530474
bhagyashreesupekar23@gmail.com
Dr Nipul Vara
Government Medical College and SSG HospitalÂ
Government Medical College and SSG Hospital , Ground Floor, OPD-01 Baroda Medical college, Jail Rd, Indira Avenue, Â
Vadodara GUJARAT
9426074084
nipulvara@yahoo.in
Dr Praduman Vaidya
Jehangir Clinical Development Centre.Pvt.Ltd
Department of Dermatology, Ground floor, OPD, Room-01 Jehangir Hospital Premises, 32 Sassoon Road, Bund Garden Rd, Sangamvadi Pune MAHARASHTRA
9822400964
drpvaidya@gmail.com
Dr Surendran K A K
K R Hospital, Mysore Medical College & Research Institute
K R Hospital, Mysore Medical College & Research Institute, Department of Skin, K R Hospital, Mysore Medical College & Research Institute, Irwin Road Mysore
Mysore KARNATAKA
9448425480
skinsurendrankak@gmail.com
Dr Venkata Chalam
King George Hospital
King George Hospital, Department of Dermatology, 1st floor, Clinical Research room, King George Hospital, Maharanipeta Visakhapatnam ANDHRA PRADESH
Shree Hospital & Critical Care Centre,
Department of Dermatology Second floor,
799,Om Nagar Opp.Tajshree Building Sakkaradara square
Nagpur MAHARASHTRA
9730310637
drshyamalb@gmail.com
DrRashmi Mahajan
Sumandeep Vidyapeeth and Dhiraj general hospitalÂ
Sumandeep Vidyapeeth and Dhiraj general hospitalÂ
Ground Floor , Dermatology Department,
Sumandeep Vidyapeeth and Institution Deemed to be University & Dhiraj Hospital, At & Po Piparia, ta. Waghodia Vadodara GUJARAT
LPR Ethics Committee, Lifepoint Multispeciality Hospital, Wakad, Pune
Approved
Penta-med Ethics committee, Medipoint Hospital private Limited, Pune
Approved
Shivam Ethics committee
Approved
SHREE HOSPITAL ETHICS COMMITTEE
Approved
Sumandeep Vidyapeeth Instituinal Ethics Commitee
Approved
Supe Hospital Ethics Committee, Nashik
Submittted/Under Review
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
Intervention
Clindamycin Phosphate Topical Lotion Eq. 1% Base
Subject have to apply a thin film of lotion over entire area of affected skin of face, using fingertips twice daily, in the morning and evening for 84 days.
Comparator Agent
Clindamycin Phosphate Topical Lotion Eq. 1% Base
Subject have to apply a thin film of lotion over entire area of affected skin of face, using fingertips twice daily, in the morning and evening for 84 days.
Inclusion Criteria
Age From
12.00 Year(s)
Age To
40.00 Year(s)
Gender
Both
Details
A subject should fulfill all the following criteria to be included in the present
study:
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.
4) Willing to provide written informed consent for participation in the study and having ability to comprehend the nature and purpose of the study.
In case of subject with age <18 years, legally acceptable representatives (LAR; e.g. parent/guardian/care-taker) must provide consent and Written Assent Form will be taken from subjects if they are able to comprehend the nature of the study.
Subject must be literate for inclusion in the study.
5) Willing to be available for the entire study period and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures, including anticipated ability to follow instructions for IP application and related usage, as per study protocol.
In case of children or among individuals not been able to follow instructions for IP application and related usage themselves, LAR (e.g. parent/guardian/care-taker) will be responsible for compliance of IP application and its related usage.
6) Willing to refrain from use of all other topical acne medications or antibiotics (other than study treatment) during the 12-week treatment period.
7) Subject not living in the same household as currently enrolled subjects (Other member of same house can be enrolled in the study, if current enrolled subject have completed the study).
8) In case of male subjects:
a) Subjects either abstain from sexual intercourse or who are willing to use adequate contraception (e.g. Use of condoms with or without spermicide ) during sexual intercourse with female partners of child bearing potential from screening day till 7 days after last dose of the study.
In case of female subjects:
a) Negative urine pregnancy test during screening and subsequent visits.
b) Subjects with child bearing potential or those within their first two years of onset of menopausal syndrome must either abstain from sexual intercourse, or must be willing to use acceptable methods of birth control from screening day till 7 days after last dose of the study.
(Reliable/acceptable birth control methods include barrier methods such as diaphragm/condom with or without spermicide or who are surgically sterile (bilateral tubal ligation, bilateral salpingectomy, bilateral oophorectomy or hysterectomy has been performed), or hormonal contraceptive
(oral, implant, injectable, or transdermal contraceptives) or abstinence practice).
Willing to maintain constant any estrogen or oral contraceptive therapy during the 12-week treatment period.
ExclusionCriteria
Details
A subject fulfilling any one of the following criteria should be excluded from the study:
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) Subjects who have acne conglobata, acne fulminans, nodulocystic acne and secondary acne (e.g.: chloracne and drug induced acne).
3) Excessive facial hair (e.g. beards, sideburns, moustaches, etc.) that would interfere with diagnosis or assessment of acne vulgaris. Well-trimmed moustaches are allowed.
4) History of hypersensitivity or allergy to Clindamycin or Lincomycin and/or any of the study medication ingredients.
5) History of regional enteritis, ulcerative colitis, or antibiotic-associated colitis.
6) Use within 6 months prior to baseline of oral retinoids (e.g. Accutane®) or therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed).
7) Use for less than 3 months prior to baseline of estrogens or oral contraceptives; use of such therapy is allowed if it will remain constant throughout the study. Use of hormonal contraceptives should not be initiated or changed during the study.
8) Use on the face within 1 month prior to baseline of: 1) cryodestruction or chemodestruction, 2) dermabrasion / microdermabrasion, 3) photodynamic therapy, 4) acne surgery, 5) intralesional steroids, 6) X-ray therapy, or 7) chemical or laser peel.
9) 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.
10) Use within 2 weeks prior to baseline of: 1) topical steroids, 2) topical retinoids, 3) topical acne treatments including over-the-counter preparations, 4) topical anti-inflammatory agents, 5) medicated cleansers/shampoo or 6) topical antibiotics.
11) Use of neuromuscular blocking agents within 14 days prior to baseline.
12) Use of astringents and toners for less than 2 weeks prior to the start of the study. The subject must have had an established regimen for at least 2 weeks prior to enrolment and must not have anticipated changing their regimen during the conduct of the entire study.
13) Use within 2 weeks prior to baseline of: 1) abradants, facials, peels containing glycolic or other acids, masks; 2) washes or soaps containing benzoyl peroxide, salicylic acid, or Sulfacetamide sodium; 3) non-mild facial cleansers; 4) moisturizers that contained retinol, salicylic acid or α-or β-hydroxy acids.
14) 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.
15) Use of tanning booths or tanning lamps or excessive/prolonged exposure to the sun within 1 week prior to baseline and an unwillingness to refrain from use during the study.
16) With significant medical history of or are currently immunocompromised or receiving immunomodulators/biologics since last 3 months of baseline.
17) Subject with any clinically significant unstable systemic or dermatologic medical disorder that, in the opinion of the investigator, will interfere with the study results or increase the risk of adverse events (AEs).
18) Any condition, medical, psychological, or social that would interfere with participation in the study (apart from acne vulgaris).
19) History of drug or alcohol abuse within last 6 months of baseline.
20) Receipt of any drug as part of a research study within 30 days before baseline.
21) Family members of employees of the clinic or Investigator or institutionalized subject.
22) Subject who, in the opinion of the Investigator, would be non-compliant with the requirements of the study protocol.
23) In case of female subject:
Pregnant or likely to become pregnant during the study period;
Lactating or nursing subject.
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 (Day 84) for inflammatory
(papules and pustules) lesion count.
Mean percent change from baseline to week 12 (Day 84) in the noninflammatory
(open and closed comedones) lesion count.
Week 12 (Day 84)
Secondary Outcome
Outcome
TimePoints
Proportion of subjects with a clinical response of “success†at week 12.
Week 12 (Day 84)
Target Sample Size
Total Sample Size="915" Sample Size from India="915" Final Enrollment numbers achieved (Total)= "0" Final Enrollment numbers achieved (India)="915"
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
Acne is a primary inflammatory disorder involving the
pilosebaceous unit. The pathogenesis is multifactorial, involving four key
factors with interrelated mechanisms: increased sebum production,
hyperkeratinization of the follicular infundibulum, inflammation, and
Cutibacterium acnes (formerly Propionibacterium acnes). Acne vulgaris is a
common disorder of the pilosebaceous unit, affecting approximately 85% of
persons 12 to 25 years of age in the United States. Acne often persists into
adulthood, with 26% of women and 12% of men reporting acne in their 40s.
Adolescents and adults with acne have higher rates of anxiety, low
self-worth, and depression than those without acne. Risk factors for the
development of acne include a family history of severe acne, the polycystic
ovary syndrome (PCOS), the metabolic syndrome, and rare genetic conditions
(e.g., Apert’s syndrome).
A diagnosis of acne is typically made by means of clinical
evaluation. Patients should be asked about family history, symptoms, and signs
that are suggestive of hyperandrogenism or another endocrine disorder,
including cortisol or growth hormone excess. Patients should also be queried
about the use of medications that have been associated with acne or the
exogenous androgens commonly results in acne flaring.
The primary lesion types in acne are comedones (open or closed
non-inflammatory lesions) and inflammatory lesions (papules, pustules, and
nodules). The typical distribution involves the sebaceous gland–rich areas of
the face, upper back, chest, and shoulders.
Treatment is based on
the types of lesions as well as on their severity and distribution. Although no
universal grading scale has been recognized, the documentation of severity
(clear, almost clear, mild, moderate, or severe) guides treatment.
Sponsor is developing a
generic formulation of Clindamycin phosphate Topical Lotion
Eq. 1% Base similar to
the reference product Clindamycin Phosphate Topical Lotion Eq.
1% Base, distributed by
Greens tone LLC, Peapack, NJ 07977; Nov 2018.
The objectives of the
present study will be:
To assess therapeutic bioequivalence between
test product and reference product inthe treatment of Acne
Vulgaris.
To assess superiority of test product and
reference product over placebo in the
treatment of Acne
Vulgaris.
To assess safety and tolerability profiles of test product,
reference product and placebo in the treatment of Acne Vulgaris.
This is a Randomized, Double-Blind, Multicenter, Placebo
Controlled Study where 915 male and female patients between age of 12 to 40
years (both inclusive) will be enrolled in any one of the three arm which are
in ratio of 2:2:1 of Test product, Reference product and Placebo. The study
drug will be masked to make its appearance identical for all three treatment
arms. Subjects will be in the study for around 84 days that includes screening
periods of 7 days and treatment period of 12 weeks. Post this, subject will be
telephonically followed up at 7 day (+/-2 days) for safety evaluation.
Given below is the visit schedule for subject during the study:
Visit 1: Screening (Within 7 days prior to
randomization)
Visit
2: Baseline and randomization (Day 0)
Visit
3: Interim visit (Safety and compliance; Day 15 ±2 days)
Visit
4: Interim visit (Safety and compliance; Day 36 ±4 days)
Visit
5: Interim visit (Safety and compliance; Day 57 ±4 days)
Visit
6: End of treatment visit (Primary endpoint evaluation; Day 84 ±4 days)
Telephonic
Follow-up: 7 days after Visit-6 (±2 days)
The end of the study will be the date of the last study visit for
the last subject in the study. At the end of the treatment period, subjects
will be prescribed appropriate medications at the investigator’s discretion, if
required. The study will commence only after the approval from the Local
Regulatory Approval (DCGI) and Institutional Ethics Committee at individual
site.