A comparative clinical trial to study the effectiveness of anti-acne drug Tretenoin gel preparation in reducing the incidence of acne recurrence

Recruiting

• Conditions: Acne vulgaris,

• Registration Number: CTRI/2023/04/052062
• Lead Sponsor: Amneal Pharmaceuticals LLC

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.

This is a Randomized, Double-Blind, Multicentre, Three arm, Active and Placebo-Controlled, Parallel Study Design to Evaluate the Bioequivalence (with Clinical Endpoint) of Tretinoin Gel microsphere,

The study will be conducted as  below:

·       Visit 1: Screening visit (Up to 3 Days prior to Randomization)

·       Visit 2: Day 1: Baseline/Randomization visit

·       Visit 3: Day 15 (± 2 days): First Interim visit (Week 2)

·       Visit 4: Day 29 (± 4days): Second Interim visit (Week 4)

·       Visit 5: Day 43 (± 4 days): Third Interim visit (Week 6)

·       Visit 6: Day 57 (± 4 days): Fourth Interim visit (Week 8)

·       Visit 7: Day 78 (± 4 days): Fifth Interim visit (Week 11)

·       Visit 8: Day 85 (± 4 days): End of Treatment/Early Termination Visit (Week 12).

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Detailed Description

Not available

Study Timeline

• Study Start: 2023-04-30
• Last Update Posted: 2023-05-15

Recruitment & Eligibility

• Status: Open to Recruitment
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Healthy male and non-pregnant, non- lactating female subjects aged 12 to 40 years (both inclusive) and having confirmed diagnosis of Acne Vulgaris.
• Subjects who are willing and able to give their IRB/IEC approved written informed consent/assent (as applicable) to participate in the study. In case of a minor, their parent/guardian is willing and able to give their IRB/IEC approved written informed consent.
• Subjects must be willing and able to understand and comply with the requirements of the protocol, including attendance at the required study visits.
• Subjects 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) on the face. Note: For the purposes of study treatment and evaluation, these lesions should be limited to the facial treatment area. All lesions will be counted, including those present on the nose. Subjects may have acne lesions on other areas of the body which will also be excluded from the count, treatment, and the Investigator’s Global Assessment (IGA) evaluation (e.g., on the back, chest and arms).
• Investigator’s Global Assessment (IGA) of acne severity, grade should be 2, 3 or 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.
• 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 last 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 6 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.
• All male subjects must agree to use accepted methods of birth control with their partners, from the day of first dose administration to 30 days after the last administration of study drug. Abstinence is an acceptable method of birth control. Female partners should use an acceptable method of birth control.
• Subjects who use make-up are ready to use the same brands/types of make-up for minimum period of 14 days prior to study entry and agree to not change make up brand/type or frequency of use throughout the study.

Exclusion Criteria

• 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, acne form eruptions caused by medications, steroid acne, steroid folliculitis, or bacterial folliculitis).
• 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 tretinoin, retinoids, or any of the study medication ingredients.
• 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 must remain constant throughout the study.
• Use on the face within 1 month prior to baseline (Randomization) cryo-destruction or chemo-destruction, dermabrasion / microdermabrasion, photodynamic therapy, acne surgery, intralesional steroids, X-ray therapy.
• Use within 1 month prior to baseline (Randomization) 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.
• Use within 2 weeks prior to baseline (Randomization) of topical steroids, topical retinoids and topical acne treatments including over-the-counter preparations, topical anti- inflammatory agents, medicated cleansers/shampoo or topical antibiotics.
• Use within 2 weeks prior to baseline (Randomization) 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.
• 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.
• 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.
• 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.
• Subjects with planned unprotected and intense UV exposure during the study (mountain sports, UV radiation, sunbathing, etc.).
• A significant medical history of or are currently immunocompromised or receiving immunomodulators/ biologics since last 3 months.
• Subjects with clinically significant vital sign abnormality.
• Subjects with clinically significant unstable medical disorders, life-threatening disease, or current malignancies.
• Subjects who engage in activities that involve excessive or prolonged exposure to sunlight or weather extremes, such as wind or cold.
• History of drug or alcohol abuse within last 6 months.
• Use of anti-pruritic, including antihistamines, within 24 hours of baseline visit.
• Lived in the same household as currently enrolled subjects.
• Female subjects who are breast-feeding or planning to become pregnant.
• Subjects who have been treated with an investigational drug or investigational device within a period of 30 days prior to study enrolment.
• Subjects with clinically significant abnormal laboratory value which may affect the participation of the subject in the study.
• 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.
• Subjects having symptoms of coronavirus disease 2019 (COVID-19) as per principal investigator discretion will be having Covid sign& symptoms assessment.

Study & Design

• Study Type: BA/BE
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1.Mean percent change from baseline to week 12 in the inflammatory (papules and pustules) lesion count	Baseline and week 12
2.Mean percent change from baseline to week 12 in the Noninflammatory (open and closed comedones) lesion count	Baseline and week 12

Secondary Outcome Measures

Name	Time	Method
1.Proportion of subjects with a clinical response of IGA score compare to baseline at week 12.	2.Proportion of subjects with a clinical response of “success†at week 12.

Trial Locations

Locations (3)

Aartham Multi Super Speciality Hospital,; 🇮🇳 Ahmadabad, GUJARAT, India

Aatman Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

SMVS Swaminarayan Hospital; 🇮🇳 Gandhinagar, GUJARAT, India

Aartham Multi Super Speciality Hospital,

🇮🇳Ahmadabad, GUJARAT, India

Dr Anshul Warman

Principal investigator

9662043716

anshulwarman@rediffmail.com