Therapeutic Equivalence of Fluorouracil Cream, 5% Compared With Fluorouracil 5% Topical Cream of MylanPharmaceuticals Inc., U.S.A in the Treatment of Actinic Keratosis

NCT05078827 | Completed Phase 3 FDA Drug

• 1 other identifier: CBCC/2021/012
• Study Type: interventional
• Target: 458
• Locations: 1 country
• Sites: 7

Brief Summary

Fluorouracil is recommended for the topical treatment of multiple actinic or solar keratoses. In the 5% strength, it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites.

Conditions

Actinic Keratoses

Outcome Measures

Primary Outcomes (3)

• Therapeutic equivalence with Reference product

  Therapeutic equivalence will be evaluated for the primary endpoint at Visit 4 in the PP population. If the 90% confidence interval on the absolute difference between the proportion of subjects who are considered a complete cure in the Test and the Reference product groups (pT - pR) is contained within \[-20%, +20%\], then therapeutic equivalence of the Test product to the Reference product will be considered to have been demonstrated

  6 weeks

• Superiority to Placebo

  The superiority of the Test and Reference products against the Placebo product will be evaluated for the primary endpoint at Visit 4 in the modified Intent-to-Treat (mITT) population using the last observation carried forward (LOCF). If the proportion of subjects who are considered a complete cure in the Test and the Reference product groups is numerically and statistically superior to that of the Placebo (p \< 0.05; using a two-sided Cochran-Mantel-Haenszel \[CMH\] test, stratified by clinical site), then the superiority of the Test and Reference products over Placebo will be concluded

  6 weeks

• Primary Efficacy End Point

  The primary efficacy endpoint is the proportion of subjects in each treatment group with treatment success, defined as 100% clearance of all AK lesions (baseline or target AK lesions and any new AK lesions) within the designated treatment area (i.e., complete cure), assessed at study Week 6 (Day 43 ± 4, which is 4 weeks after completion of 2 weeks of treatment)

  6 weeks

Secondary Outcomes (1)

• Safety Analysis

  6 weeks

Study Arms (3)

Comparator Arm

ACTIVE COMPARATOR

Reference Product (B): Fluorouracil 5% Topical Cream of Mylan Pharmaceuticals Inc., Morgantown, WV 26505 U.S.A.

Drug: Reference Product (B): Fluorouracil 5% Topical Cream of Mylan Pharmaceuticals Inc., Morgantown, WV 26505 U.S.A.

Arms and Interventions

EXPERIMENTAL

Test Product (A): Fluorouracil Cream, 5% of Encube Ethicals Pvt. Ltd., India

Drug: Test Product (A): Fluorouracil Cream, 5% topical cream

Placebo Arm

PLACEBO COMPARATOR

Placebo Product (C): Test vehicle cream for fluorouracil 5% of Encube Ethicals Pvt. Ltd., India

Drug: Placebo Product (C): Test vehicle cream for fluorouracil 5% of Encube Ethicals Pvt. Ltd., India

Interventions

Test Product (A): Fluorouracil Cream, 5% topical cream DRUG

Apply cream twice daily in an amount sufficient to cover the lesions. Fluorouracil should be applied preferably with a nonmetal applicator or suitable glove. If Fluorouracil is applied with the fingers, the hands should be washed immediately afterward.

Also known as: Experimental

Arms and Interventions

Reference Product (B): Fluorouracil 5% Topical Cream of Mylan Pharmaceuticals Inc., Morgantown, WV 26505 U.S.A. DRUG

Apply cream twice daily in an amount sufficient to cover the lesions. Fluorouracil should be applied preferably with a nonmetal applicator or suitable glove. If Fluorouracil is applied with the fingers, the hands should be washed immediately afterward.

Also known as: Active Comparator

Comparator Arm

Placebo Product (C): Test vehicle cream for fluorouracil 5% of Encube Ethicals Pvt. Ltd., India DRUG

Apply cream twice daily in an amount sufficient to cover the lesions. Fluorouracil should be applied preferably with a nonmetal applicator or suitable glove. If Fluorouracil is applied with the fingers, the hands should be washed immediately afterward.

Also known as: Placebo Comparator

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide voluntary informed consent and follow the protocol requirements
• Males or females at least 18 years of age
• Subjects with at least five (5) and no more than ten (10) clinically typical, visible, discrete, AK lesions, each at least 4 mm in diameter on the face or bald scalp. In this interpretation, if the total number of lesions on the face and bald scalp exceeds 10 and there are either 5-10 lesions on the face or 5-10 lesions on the bald scalp then select the designated treatment area that has 5-10 lesions (i.e., face or bald scalp)
• Skin pigmentation (Fitzpatrick skin type I, II, and III) that will allow differentiation of erythema assessment
• Females of childbearing potential must not be pregnant or lactating at Visit 1 (as confirmed by a negative urine pregnancy test with a sensitivity of less than 50 mIU/mL or equivalent units of human chorionic gonadotropin)
• Women of childbearing potential must agree to the use of a reliable method of contraception (e.g., total abstinence, intrauterine device, a double barrier method, oral, transdermal, injected, or implanted nonhormonal or hormonal contraceptive) throughout the study. Female patients using hormonal contraceptives should have been on the same product/dosing regimen for at least 28 days before Visit 1 and should not change this regimen during the study. A sterile sexual partner is not considered an adequate form of birth control.

You may not qualify if:

• Known hypersensitivity or allergy to Fluorouracil or any of the excipients in the Test, Reference or Placebo products
• Presence of atopic dermatitis, basal cell carcinoma, eczema, psoriasis, rosacea, squamous cell carcinoma, or other possible confounding skin conditions on the face or bald scalp
• Use within 6 months before Visit 1 on the face or bald scalp of 1) chemical peel, 2) dermabrasion, 3) laser abrasion, 4) PUVA (psoralen plus ultraviolet A) therapy, or 5) ultraviolet B therapy
• Use within 1 month before Visit 1 on the face or scalp of 1) cryo destruction or chemo destruction, 2) curettage, 3) photodynamic therapy, 4) surgical excision, 5) topical 5-fluorouracil, 6) topical corticosteroids 7) topical diclofenac, 8) topical imiquimod, 9) topical retinoids, or 10) other treatments for AK including glycolic acid or over-the-counter products containing retinol, alpha or beta hydroxy acids
• Use within 1 month before Visit 1 of 1) immunomodulators or immunosuppressive therapies, 2) interferon, 3) oral or injectable corticosteroids, or 4) cytotoxic drugs
• Known dihydropyrimidine dehydrogenase (DPD) enzyme deficiency
• Inability to understand the requirements of the study and the relative information or are unable or not willing to comply with the study protocol
• Employees of the Investigator or research center or their immediate family members
• Patients who have participated in this study previously
• Patient lived in the same household as currently enrolled subject

Sponsors & Collaborators

• Encube Ethicals Pvt. Ltd.: lead
• CBCC Global Research: collaborator

Study Sites (7)

CBCC Global Research Site 005

Bakersfield, California, 93309, United States

Location

CBCC Global Research Site 006

Cerritos, California, 90703, United States

Location

CBCC Global Research Site 004

Lauderdale Lakes, Florida, 33308, United States

Location

CBCC Global Research Site 001

Miami, Florida, 33015, United States

Location

CBCC Global Research Site 002

Miami, Florida, 33175, United States

Location

CBCC Global Research Site 003

Miramar, Florida, 33027, United States

Location

CBCC Global Research Site 007

Sugarloaf, Pennsylvania, 18249, United States

Location

MeSH Terms

Conditions

Keratosis, Actinic

Interventions

Fluorouracil

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Keratosis; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2021
• First Posted: October 15, 2021
• Study Start: March 1, 2022
• Primary Completion: November 1, 2022
• Study Completion: December 1, 2022
• Last Updated: March 14, 2023

Record last verified: 2023-03

Locations

US (7)