A Phase 3 interventional study of Test Product (A): Fluorouracil Cream, 5% topical cream and Reference Product (B): Fluorouracil 5% Topical Cream of Mylan Pharmaceuticals Inc., Morgantown, WV 26505 U.S.A. in Actinic Keratoses, sponsored by Encube Ethicals Pvt. Ltd.. Completed at 7 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-03-14.
Sponsored by Encube Ethicals Pvt. Ltd. · Phase 3, Interventional, and Treatment
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.
There is evidence that the metabolism of Fluorouracil in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner, Fluorouracil interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits the formation of ribonucleic acid (RNA). As DNA and RNA are essential for cell division and growth, the effect of Fluorouracil may be to create a thymine deficiency, which, provokes unbalanced growth and death of the cell. The effects of DNA and RNA deprivation are most marked on those cells that grow more rapidly and take up Fluorouracil at a more rapid rate. The catabolic metabolism of Fluorouracil results in degradation products (e.g., CO2, urea, α-fluoro-β-alanine), which are inactive.
Systemic absorption studies of topically applied Fluorouracil have been performed on patients with actinic keratoses using tracer amounts of 14C-labeled Fluorouracil added to a 5% preparation. All patients had been receiving nonlabeled Fluorouracil until the peak of the inflammatory reaction occurred (2 to 3 weeks), ensuring that the time of maximum absorption was used for measurement. One gram of labeled preparation was applied to the entire face and neck and left in place for 12 hours. Urine samples were collected. At the end of 3 days, the total recovery ranged between 0.48% and 0.94%, with an average of 0.76%, indicating that approximately 5.98% of the topical dose was absorbed systemically. If applied twice daily, this would indicate systemic absorption of topical Fluorouracil to be in the range of 5 to 6 mg per daily dose of 100 mg. In an additional study, negligible amounts of labeled material were found in plasma, urine, and expired CO2 after 3 days of treatment with topically applied 14C-labeled Fluorouracil.
343 studies on the registry are indexed under Keratosis, Actinic; 29 are open to participants now.
This study's enrollment of 458 is above the median of 60 across 295 interventional studies indexed under Keratosis, Actinic.
Browse Keratosis, Actinic studies →Encube Ethicals Pvt. Ltd. is the lead sponsor of 4 studies on the registry; none are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Test Product (A): Fluorouracil Cream, 5% of Encube Ethicals Pvt. Ltd., India
Drug: Test Product (A): Fluorouracil Cream, 5% topical cream
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
Drug page: Fluorouracil
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
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
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
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
Time frame: 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
Time frame: 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)
Time frame: 6 weeks
Safety Analysis
All Safety analysis will be based on the Safety population. Adverse events will be classified using standard MedDRA terminology Version 24.0 or higher and summarized by treatment group. Summary tables comparing the type, incidence, date of onset, date of resolution, severity, action taken, outcome, and Investigator's opinion of relationship to the study product will be prepared by treatment group. If sufficient data exist, AE frequencies will be compared between treatments using Fisher's exact test. If the global Fisher's exact test is statistically significant among the three treatment groups at the 5% alpha level (i.e., p \< 0.05), then Fisher's exact test using only the Test and Reference groups may be performed to identify any potential statistically significant differences that are clinically relevant between the two active treatment groups
Time frame: 6 weeks
This study is completed, as verified in Mar 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Fluorouracil
Encube Ethicals Pvt. Ltd.