Therapeutic Equivalence Study of Clindamycin and Tretinoin Gel in Acne Vulgaris: A Randomized, Double-Blind, Placebo-Controlled Trial
- Trial ID
- 2024-518430-91-00
- Protocol
- CLITRET/VER
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to establish the **therapeutic equivalence** of topical treatment with clindamycin + tretinoin/Verisfield gel (Test product) and Acnatac®/Meda gel (Reference product) in the treatment of **acne vulgaris**. This will be achieved by demonstrating that the two products are therapeutically equivalent and superior to the placebo, through assessing the changes from baseline in the facial inflammatory and non-inflammatory lesion counts at Week 12. The clinical relevance of this objective lies in providing evidence for the efficacy of the test product as a viable alternative to the reference product, potentially offering more treatment options for patients with acne vulgaris.
Secondary objectives include:
- Comparing the efficacy of the test product against the reference product in terms of success of therapy using the Investigator's Global Assessment (IGA) scale.
- Comparing the safety and tolerability profile of the test product versus the reference product.
Participants
The clinical trial involves a total of **300 participants** diagnosed with **acne vulgaris**, a common skin condition. The study population includes both male and non-pregnant, non-lactating female subjects aged between 12 and 40 years. Participants were selected based on specific criteria, including a clinical diagnosis of mild to severe facial acne vulgaris, defined as Grade 2, 3, or 4 based on the Investigator's Global Assessment (IGA) at Baseline. Subjects must have at least 25 non-inflammatory lesions and 20 inflammatory lesions on the face, with no more than 2 nodulocystic lesions. All participants are required to have maintained consistent use of non-medicated facial and hair products for at least 14 days prior to the study and agree to continue this regimen throughout the trial. The trial population is in good general health, free from any conditions that could interfere with the study's integrity or pose an unacceptable risk. Both genders are included, and the study considers vulnerable populations. Participants must be willing to comply with study instructions, including the application of investigational products and adherence to scheduled visits. Additionally, female participants of childbearing potential must use an acceptable form of birth control and have a negative pregnancy test at Baseline.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, parallel, three-arm study to evaluate the therapeutic equivalence of clindamycin + tretinoin/Verisfield gel compared to Acnatac®/Meda gel and a placebo in the treatment of **acne vulgaris**. The trial aims to demonstrate that the test and reference products are therapeutically equivalent and superior to the placebo by assessing changes in facial inflammatory and non-inflammatory lesion counts over a 12-week period. The study is expected to conclude by December 31, 2025, with recruitment having commenced on January 1, 2023.
Participants will be involved in the study for a total of 12 weeks, during which they will attend several study visits. The initial visit will serve as the inclusion (screening) visit, where eligibility criteria are confirmed, and informed consent is obtained. Participants must be male or non-pregnant, non-lactating females aged between 12 and 40 years, with a clinical diagnosis of mild to severe facial acne vulgaris. They must have a specified number of non-inflammatory and inflammatory lesions and agree to maintain consistent use of non-medicated facial and hair products throughout the study.
Following the screening visit, participants will be randomized into one of the three treatment arms. Subsequent follow-up visits will occur at regular intervals to monitor progress, adherence to the treatment regimen, and any adverse events. The primary endpoints include the percent change from baseline to week 12 in facial inflammatory and non-inflammatory lesion counts. Secondary endpoints involve assessing the clinical response according to the Investigator's Global Assessment (IGA) scale, incidence of adverse events, and application site reactions.
The end-of-study visit will mark the conclusion of the participant's involvement, where final assessments are conducted, and data is collected for analysis. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study protocols, or at the discretion of the investigator if continued participation poses a risk to the participant's health. The trial is not categorized as low intervention and is classified under therapeutic exploratory and confirmatory clinical trials.
Treatment
The clinical trial involves the evaluation of **Clindamycin + Tretinoin/Verisfield gel**, an experimental medication formulated as a gel for the treatment of acne vulgaris. This gel contains 10 mg/g (1%) **clindamycin** (as clindamycin phosphate) and 0.25 mg/g (0.025%) **tretinoin**. The pharmaceutical form is a gel, intended for **external use** only. The maximum daily dose is 0.5 grams, with a total treatment period of up to 12 weeks. The gel is applied topically, and participant compliance is monitored throughout the study to ensure adherence to the dosing schedule.
The study also includes a comparator treatment, **Acnatac gel**, which contains the same active ingredients, clindamycin and tretinoin, in identical concentrations. This product is also administered as a gel for external use, with a maximum daily dose of 0.5 grams over a 12-week period. The comparator serves to establish the therapeutic equivalence of the test product.
A placebo gel is utilized as a control in this trial to further assess the efficacy of the experimental and comparator treatments. The placebo is formulated to match the appearance and application method of the active gels but does not contain the active substances. The placebo is applied in the same manner, with a maximum daily dose of 0.5 grams for up to 12 weeks.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the therapeutic equivalence of the test product, clindamycin + tretinoin/Verisfield gel, and the reference product, Acnatac®/Meda gel, in the treatment of **acne vulgaris**. The primary endpoints for efficacy assessment include the percent change from baseline to week 12 in the facial inflammatory lesion count (papules and pustules) and the facial non-inflammatory lesion count (open and closed comedones) in each of the three treatment arms. These changes will be measured at baseline and at week 12 to determine the efficacy of the treatments.
Secondary endpoints will include the proportions of participants achieving a clinical response of 'success' to therapy at week 12 according to the Investigator's Global Assessment (IGA) scale. Additionally, the incidence and severity of treatment-emergent serious and non-serious adverse events (AEs) and adverse drug reactions (ADRs) will be monitored, along with the proportions of participants experiencing application site reactions such as erythema, dryness, burning/stinging, erosion, edema, pain, and itching. The study will also track the proportions of participants with permanent treatment discontinuations and the reasons for these discontinuations over the 12-week study period.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Male or non-pregnant non-lactating female aged ≥ 12 and ≤ 40 years at the time of consent/assent.
- Subject has a clinical diagnosis of mild to severe facial acne vulgaris defined as Grade 2, 3, or 4 based on the IGA at Baseline.
- Subject must have ≥ 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) on the face at Baseline.
- Subject has used the same type and brand of non-medicated makeup, cleanser or other non-medicated facial products and hair products for at least 14 days prior to Baseline and agrees to continue and not change his/her non-facial general skin care and hair care products and frequency of use for the entire study period.
- Subject, in the Investigator's opinion, is in good general health and free of any disease state or physical condition that might impair evaluation of facial acne vulgaris or otherwise impact the integrity of the study, or exposes the subject to an unacceptable risk by study participation.
- If FOCBP1,2, willingness to use an acceptable form of birth control during the study [i.e., must have been using accepted methods of birth control or must agree to continue to practice abstinence, from 30 days prior to study entry to 30 days after the last administration of the IP]. FOCBP must have a negative urine pregnancy test (UPT)3 at Baseline.
- Subject and parent(s)/guardian (if applicable) are willing and able to apply the IP as directed, comprehend and comply with study instructions, and follow the requirements of the study (including availability on scheduled visit dates) for the duration of the study.
- Subject [and their parents(s)/guardian/legally authorized representative(s), as applicable] is (are) able to understand and willing to provide voluntary written informed assent/consent before any studyrelated procedure is performed.
- Subject must be willing and able to refrain from use of all other topical products applied to face (moisturizer, new brands of make-up, creams, lotions, powders or any topical product other than the assigned treatment to the treatment area and the study-supplied cleanser and sunscreen), all acne medications and antibiotics for acne present on the face during the 12-week treatment period.
Exclusion Criteria
- Subject is pregnant, breastfeeding or is planning a pregnancy or breastfeed throughout the study period and for 30 days after the last administration of the IP.
- Subject has pustular and deep cystic nodular acne varieties (acne conglobata and acne fulminans), or other forms of acne (e.g., acne mechanica).
- Subject has Crohn's disease, regional enteritis, ulcerative colitis or history of antibiotic-associated colitis.
- Subject has atopic dermatitis or a history of acute eczemas, rosacea and perioral dermatitis, and any skin condition that, in the Investigator's opinion, could interfere with the diagnosis or assessment of acne vulgaris (e.g., on the face: rosacea, dermatitis, psoriasis, squamous cell carcinoma, eczema, acneiform eruptions caused by medications, steroid acne, steroid folliculitis, or bacterial folliculitis).
- Subject has a personal history of skin cancer.
- Excessive facial hair (e.g. beards, sideburns, moustaches, etc.), facial tattoos, or other facial attributes that could interfere, in the Investigator's opinion, with diagnosis or assessment of acne vulgaris.
- Subject has any contraindication to clindamycin phosphate and tretinoin or history of hypersensitivity or allergy to tretinoin, retinoids, clindamycin or to any of the study medication excipients or lincomycin (see section 11.1).
- Subject has used for less than 3 months (90 days) prior to Baseline oestrogens or oral contraceptives; subjects treated with such agents 30 or more consecutive dates immediately prior to Baseline need not be excluded unless the subject expects to change dose, drug or discontinue this use during the study. If the subject had used hormonal birth control and had stopped, this should have occurred more than 3 months prior to Baseline.
- Subject has used antipruritics, including antihistamines within 24 hours prior to Baseline.
- Subject has used any of the following topical preparations or procedures on the face: - within 1 month (30 days) prior to Baseline: a. cryodestruction or chemodestruction b. dermabrasion c. photodynamic therapy including other light-based and laser therapies d.acne surgery e. intralesional steroids f. x-ray therapy. - within 2 weeks prior to Baseline: a. topical steroids b. topical retinoids (e.g., tazarotene, adapalene, and tretinoin) c. topical acne treatments including, but not limited to, OTC acne cleansers, soaps, washes or treatments, benzoyl peroxide, antibiotics, azelaic acid, dapsone, sulfa based products, corticosteroids, and salicylic acid d. topical anti-inflammatory agents e. topical antibiotics - at any time prior to Baseline: a. other topical therapy which may materially affect the subject's acne, in the Investigator's opinion.
- Subject has used any of the following systemic medication: - within 6 months prior to Baseline: a. oral retinoids (e.g., Accutane®) b. therapeutic vitamin A supplements of greater than 10,000 units/day (multivitamins are allowed). - within 3 months prior to Baseline: a. hormonal therapy for acne management - within 1 month prior to Baseline: a. androgen receptor blockers (e.g., spironolactone, flutamide) b. steroids (including intramuscular, intra-articular, and intralesional injections) c. antibiotics d. treatment for acne vulgaris (other than oral retinoids, which require a 6-month washout) e. anti-inflammatory agents f. immunosuppressive drugs. - within 2 weeks prior to Baseline: a. neuromuscular blocking agents such as botulinum toxin type A (e.g., BOTOX, DYSPORT) - at any time prior to Baseline: a. other systemic therapy which may materially affect the subject's acne, in the Investigator's opinion.
- Subject with known evidence of lack of adherence to medications and/or lack of ability to follow physician's recommendations (e.g., due to alcoholism, drug dependency, mental incapacity) in the opinion of the Investigator.
- Previous treatment with the Reference product.
- Subject engages in activities that involve excessive or prolonged exposure to sunlight, or is required to have considerable sun exposure due to occupation, or with inherent sensitivity to the sun, or is exposed or planned to be exposed to artificial tanning devices.
- Subject is planning surgery during the study.
- Subject currently receives treatment with any investigational drug/device/intervention or has received any investigational product within 30 days or 5 half-lives of the investigational agent (whichever is longer) before Baseline.
- Subject and parent/guardian (if applicable) are unable to communicate or cooperate with the Investigator due to language problems or mental incapacity.
- Subject with close affiliation with the Investigator (i.e., family members) or study staff or subject who is involved in the planning and/or conduct of the study (applies to Investigator, study staff, and Sponsor).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Greece | Not Recruiting | 01 Jan 2023 | 300 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Clindamycin + tretinoin/Verisfield gel [10 mg/g (1%) clindamycin (as
clindamycin phosphate) + tretinoin 0.25 mg/g (0.025%) gel] | Test | GEL | EXTERNAL USE | 0.5 | 12 | PRD10216271 |
Clindamycin +Tretinoin gel | Placebo | N/A | — | — | — | N/A |
Acnatac 10 mg/g + 0,25 mg/g γέλη | Comparator | ΓΈΛΗ | EXTERNAL USE | 0.5 | 12 | PRD1852588 |