Pirfenidone Plus M-DDO Gel in Moderate and Severe Acne
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03076320|
Recruitment Status : Recruiting
First Posted : March 10, 2017
Last Update Posted : June 7, 2018
Acne vulgaris is a complex skin disorder involving multiple abnormalities of the pilosebaceous unit. Acne is the most common skin disease during puberty and worsens throughout adolescence. However, epidemiological studies suggest that acne can arise at any age, most frequently affecting individuals between puberty and 30 years of age, with 79%-95% of subjects aged between 16 years and 18 years and 80% of subjects between puberty and 30 years of age. Acne is considered the main reason for consultation with the dermatologist in institutional and private clinical practice.
Clinical features include seborrhoea, non-inflammatory lesions, inflammatory lesions and various degrees of scarring. There are many classifications of acne and scarring severity. Moderate to severe acne is about 15-20%.
Facial acne scarring affects both sexes equally and occurs to some degree in up to 95% of cases. There is a significant correlation between the initial acne grade and the overall severity of scarring at all sites and in both sexes. This would suggest that treatment aimed at reducing the severity of acne might reduce the incidence of scarring. Both superficial inflammatory acne lesions as well as deep nodular lesions seem capable of producing scars.
Conventional therapies recommended for the treatment of acne vulgaris include retinoids, benzoyl peroxide (BPO), antibiotics, and hormonal therapy. Combination therapy using agents with complementary mechanisms provides the opportunity to target multiple pathogenetic causes of acne vulgaris.
The combination in gel with 0.1% adapalene and 2.5% BPO is a once-daily treatment of acne vulgaris. In several double- blind, randomized controlled trials (RCTs), the Adapalene-BPO (A-BPO) combination therapy applied once daily for 12 weeks significantly reduced the number of both inflammatory and non-inflammatory lesions in subjects with moderate acne vulgaris. In Mexico there is an available commercial product of this combination (Effezel®; Galderma). The limitation of this topical therapy is the low tolerability by patients as they can experiment several levels of irritation, erythema, dryness, desquamation, burning, and itching), and patients are advised to expect these side effects, which contribute to discontinue therapy if it becomes severe.
On the other hand, 5-methyl-1-phenyl-2-(1h)-pyridone or pirfenidone (PFD) is a wide-spectrum antifibrotic drug that modulates diverse cytokines action, involving TGF-β, TNF-α, epidermal growth factor, platelet-derived growth factor, VEGF, IGF-1, fibroblast growth factor, interferon-γ, interleukin (IL)-1, IL-6, and IL-8 and it has shown promising effects in vitro and in vivo settings. Also, PFD has proven effective in the prevention and regression of pulmonary fibrosis, peritoneal sclerosis, hepatic cirrhosis, uterine fibromyoma, left ventricular fibrosis, renal interstitial fibrosis, and breast capsular contracture in experimental models. A recently open phase II clinical trial evaluated the therapeutic use of PFD gel in localized scleroderma. Results showed it acts on both the inflammatory and the fibrotic phases.
The other component of Zaxcell is modified-diallyl disulfide oxide (M-DDO) an antimicrobial and antiseptic agent, which has been proved in patients with chronic diabetic ulcer as a potent germicide and has show to increase the beneficial effect of PFD preventing infections, accelerating and improving ulcer resolution. (Observations not published).
According to this, the investigators believe that Zaxcell (PFD + M-DDO) could play an important role in the modulation of inflammatory and scarring process in acne. The investigators hypothesis is that PFD in patients with moderate to severe acne modulates amplification of the inflammatory response, regulating the inflammasome activation, macrophage polarization and its activity in regulating the wound healing process of the skin in an early fashion.
Zaxcell is an innovative gel with a synergetic mode of action that could modulate the inflammatory response. Furthermore, has antiseptic properties and regulates the process of wound healing, fibrogenic and scarring process. In vitro and in vivo studies provide an initial body of evidence on the safety and clinical benefits of PFD, the main component of Zaxcell as a promising candidate for the treatment of moderate to severe acne.
|Condition or disease||Intervention/treatment||Phase|
|Acne Vulgaris Superficial Mixed Comedonal and Inflammatory||Combination Product: PDF+M-DDO Combination Product: A+PBO||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||82 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Outcomes Assessor)|
|Official Title:||Molecular and Clinical Study of the Effect of Zaxcell Versus Effezel in the Inflammatory and Scarring Process of Moderate and Severe Acne|
|Actual Study Start Date :||March 27, 2017|
|Estimated Primary Completion Date :||January 31, 2019|
|Estimated Study Completion Date :||March 31, 2019|
Pirfenidone with M-DDO Active ingredients: Pirfenidone 10% with modified oxide diallyl disulfide (M-DDO) 0.016% Dosage form: gel. Dosage: standard finger tip unit (0.5g for an area of 100 to 120 square centimeters).
Frequency an duration: topically applied every 12 hours for 6 months.
Combination Product: PDF+M-DDO
Participants with moderate and severe acne will be treated two times a day on the face and superior back with a smooth layer (standard finger tip unit 0.5 g for an area of 100 to 120 square centimeters) of Zaxcell (Pirfenidone with M-DDO) in form of a gel. Patients have to wait 20 min without cover those sites.
Active Comparator: A+PBO
Adapalene with benzoyl peroxide Active ingredients: 0.1% Adapalene with 2.5% benzoyl peroxide. Dosage form: gel. Dosage: standard finger tip unit (0.5g for an area of 100 to 120 square centimeters).
Frequency and duration: topically applied every 12 hours for 6 month
Combination Product: A+PBO
Participants with moderate and severe acne will be treated once a day (at night) on the face and superior back with a smooth layer (standard finger tip unit 0.5 g for an area of 100 to 120 square centimeters) of Effezel (Adapalene with benzoyl peroxide) in form of a gel. Patients have to wait 20 min without cover those sites
- Assessing change of lesions with IGA scale (Investigators' Global Assessment) [ Time Frame: 1, 2, 3, 4, 5 and 6 months ]Number or lesions
- Histopathological modification on the inflammatory lesions and improvement in the scarring process [ Time Frame: 1 and 3 months ]Biopsy from the upper back area
- 2. Expression levels of key molecules involved in acne inflammation and scar remodeling [ Time Frame: 1 and 3 months ]Biopsy from the upper back area
- Photonumeric scale [ Time Frame: 1, 3 and 6 months ]Photographs of the treated area analyzed by three-dimensional reconstruction software
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03076320
|Hospital Civil de Guadalajara Fray Antonio Alcalde||Recruiting|
|Guadalajara, Jalisco, Mexico, 44280|
|Contact: Yocasta Martínez Alvarado, MD +52 (33) 14794863 email@example.com|
|Contact: Marisol Ramirez Padilla, MD +52 (33) 31563006 firstname.lastname@example.org|
|Principal Investigator: Yocasta Martínez-Alvarado, MD|
|Sub-Investigator: Marisol Ramirez-Padilla, MD|