A multi-center, double-blind, randomized, parallel group, active and placebo-controlled in vivoclinical endpoint based bioequivalence study of Clindamycin Phosphate Topical Lotion Eq. 1%Base among subjects with Acne Vulgaris.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 915
- Locations
- 13
- Primary Endpoint
- Mean percent change from baseline to week 12 (Day 84) for inflammatory
Study Overview
Brief Summary
Acne is a primary inflammatory disorder involving thepilosebaceous unit. The pathogenesis is multifactorial, involving four keyfactors with interrelated mechanisms: increased sebum production,hyperkeratinization of the follicular infundibulum, inflammation, andCutibacterium acnes (formerly Propionibacterium acnes). Acne vulgaris is acommon disorder of the pilosebaceous unit, affecting approximately 85% ofpersons 12 to 25 years of age in the United States. Acne often persists intoadulthood, with 26% of women and 12% of men reporting acne in their 40s.
Adolescents and adults with acne have higher rates of anxiety, lowself-worth, and depression than those without acne. Risk factors for thedevelopment of acne include a family history of severe acne, the polycysticovary syndrome (PCOS), the metabolic syndrome, and rare genetic conditions(e.g., Apert’s syndrome).
A diagnosis of acne is typically made by means of clinicalevaluation. Patients should be asked about family history, symptoms, and signsthat are suggestive of hyperandrogenism or another endocrine disorder,including cortisol or growth hormone excess. Patients should also be queriedabout the use of medications that have been associated with acne or theexogenous androgens commonly results in acne flaring.
The primary lesion types in acne are comedones (open or closednon-inflammatory lesions) and inflammatory lesions (papules, pustules, andnodules). The typical distribution involves the sebaceous gland–rich areas ofthe face, upper back, chest, and shoulders.
Treatment is based onthe types of lesions as well as on their severity and distribution. Although nouniversal grading scale has been recognized, the documentation of severity(clear, almost clear, mild, moderate, or severe) guides treatment.
Sponsor is developing ageneric formulation of Clindamycin phosphate Topical Lotion
Eq. 1% Base similar tothe reference product Clindamycin Phosphate Topical Lotion Eq.
1% Base, distributed byGreens tone LLC, Peapack, NJ 07977; Nov 2018.
The objectives of thepresent study will be:
To assess therapeutic bioequivalence betweentest product and reference product in the treatment of AcneVulgaris.
To assess superiority of test product andreference product over placebo in the
treatment of AcneVulgaris.
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, PlaceboControlled Study where 915 male and female patients between age of 12 to 40years (both inclusive) will be enrolled in any one of the three arm which arein ratio of 2:2:1 of Test product, Reference product and Placebo. The studydrug will be masked to make its appearance identical for all three treatmentarms. Subjects will be in the study for around 84 days that includes screeningperiods of 7 days and treatment period of 12 weeks. Post this, subject will betelephonically 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 torandomization)
Visit2: Baseline and randomization (Day 0)
Visit3: Interim visit (Safety and compliance; Day 15 ±2 days)
Visit4: Interim visit (Safety and compliance; Day 36 ±4 days)
Visit5: Interim visit (Safety and compliance; Day 57 ±4 days)
Visit6: End of treatment visit (Primary endpoint evaluation; Day 84 ±4 days)
TelephonicFollow-up: 7 days after Visit-6 (±2 days)
The end of the study will be the date of the last study visit forthe last subject in the study. At the end of the treatment period, subjectswill be prescribed appropriate medications at the investigator’s discretion, ifrequired. The study will commence only after the approval from the LocalRegulatory Approval (DCGI) and Institutional Ethics Committee at individualsite.
Study Design
- Study Type
- Interventional
- Allocation
- Computer generated randomization
- Masking
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Eligibility Criteria
- Ages
- 12.00 Year(s) to 40.00 Year(s) (—)
- Sex
- All
Inclusion Criteria
- •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.
- •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).
- •Investigator’s Global Assessment (IGA) of acne severity grade 2, 3 or
- •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.
- •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.
- •Willing to refrain from use of all other topical acne medications or antibiotics (other than study treatment) during the 12-week treatment period.
- •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).
- •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.
Exclusion Criteria
- •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).
- •Subjects who have acne conglobata, acne fulminans, nodulocystic acne and secondary acne (e.g.: chloracne and drug induced acne).
- •Excessive facial hair (e.g. beards, sideburns, moustaches, etc.) that would interfere with diagnosis or assessment of acne vulgaris.
- •Well-trimmed moustaches are allowed.
- •History of hypersensitivity or allergy to Clindamycin or Lincomycin and/or any of the study medication ingredients.
- •History of regional enteritis, ulcerative colitis, or antibiotic-associated colitis.
- •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).
- •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 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.
- •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.
- •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.
- •Use of neuromuscular blocking agents within 14 days prior to baseline.
- •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.
- •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.
- •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.
- •With significant medical history of or are currently immunocompromised or receiving immunomodulators/biologics since last 3 months of baseline.
- •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).
- •Any condition, medical, psychological, or social that would interfere with participation in the study (apart from acne vulgaris).
- •History of drug or alcohol abuse within last 6 months of baseline.
- •Receipt of any drug as part of a research study within 30 days before baseline.
- •Family members of employees of the clinic or Investigator or institutionalized subject.
- •In case of female subject: Pregnant or likely to become pregnant during the study period; Lactating or nursing subject.
Outcomes
Primary Outcomes
Mean percent change from baseline to week 12 (Day 84) for inflammatory
Time Frame: Week 12 (Day 84)
(papules and pustules) lesion count.
Time Frame: Week 12 (Day 84)
Mean percent change from baseline to week 12 (Day 84) in the noninflammatory
Time Frame: Week 12 (Day 84)
(open and closed comedones) lesion count.
Time Frame: Week 12 (Day 84)
Secondary Outcomes
- Proportion of subjects with a clinical response of “success†at week 12.(Week 12 (Day 84))