Randomized phase 3 evaluation of trifarotene 50 µg/g cream treatment of moderate facial and truncal acne.

BACKGROUND: Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied. OBJECTIVES: Assess the safety and efficacy of trifarotene 50 µg/g cream, a novel topical retinoid, in moderate facial and truncal acne. METHODS: Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator's Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from baseline to week 12. The secondary end points were rate of success on the trunk (clear or almost clear and ≥2-grade improvement) and absolute change in truncal inflammatory and noninflammatory counts from baseline to week 12. Safety was assessed through adverse events, local tolerability, vital signs, and routine laboratory testing results. RESULTS: In both studies, at week 12 the facial success rates according to the Investigator's Global Assessment and truncal Physician's Global Assessment and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P < .001) in favor of trifarotene when compared with the vehicle. LIMITATIONS: Adjunctive topical or systemic treatments were not studied. CONCLUSION: These studies demonstrate that trifarotene appears to be safe, effective, and well tolerated in treatment of both facial and truncal acne.

Long-term safety of ketoconazole foam, 2% in the treatment of seborrheic dermatitis: results of a phase IV, open-label study.

BACKGROUND: Ketoconazole foam, 2%, is approved in the United States for seborrheic dermatitis therapy in immunocompetent patients aged ≥12 years. While short-term trials have demonstrated its safety and efficacy, seborrheic dermatitis often requires long-term treatment. OBJECTIVE: To assess the long-term safety of ketoconazole foam, 2%, twice daily, as required. METHODS: A 12-month, open-label, multicenter study. Subjects were evaluated at baseline and at weeks 4, 8, 16, 26, 39, and 52 (or early termination [ET]) for adverse events (AEs), serious AEs (SAEs), target lesion erythema, scaling, and pruritus, as well as Investigator's Static Global Assessment (ISGA) scores. Physical examinations were performed at baseline and at week 52/ET, and laboratory evaluations at baseline and at weeks 8, 26, and 52. A poststudy product-preference questionnaire was completed. RESULTS: Of 500 subjects enrolled, 498 were included in the safety population, and 363 completed the study. Overall, 57% of subjects reported ≥1 AE. Treatment-related AEs occurred in 14% of subjects, including application-site irritation (8%), application-site pain (4%), application-site pruritus (1%), and increased alanine aminotransferase (1%). Seven subjects were withdrawn because of treatment-related AEs. No SAEs (21 in 17 subjects) were considered to be related to study drug. Mean target lesion erythema, scaling, and pruritus scores improved by 2 units from baseline at all study visits; mean ISGA score improved by 1 unit at week 4 and by 2 units at subsequent visits. The foam vehicle was preferred by 67% of subjects. LIMITATIONS: Evaluation of severity was limited to target lesion; no objective measure of adherence. CONCLUSION: The long-term safety profile of ketoconazole foam, 2%, in subjects with seborrheic dermatitis was favorable and efficacy was maintained.

The efficacy and tolerability of tazarotene foam, 0.1%, in the treatment of acne vulgaris in 2 multicenter, randomized, vehicle-controlled, double-blind studies.

BACKGROUND: Tazarotene 0.1% gel and cream are effective topical treatments for acne. Tazarotene foam, 0.1% was developed to provide an alternative, safe, and effective formulation. OBJECTIVE: To evaluate efficacy and tolerability of tazarotene foam, 0.1% in adults and adolescents with acne vulgaris. METHODS: Two randomized, double-blind, vehicle-controlled, parallel-group studies were conducted at 39 centers in the United States and Canada. The first study involved 744 participants and the second 742, aged 12 to 45 years, who were randomized to receive treatment with either tazarotene foam, 0.1% or vehicle foam once daily for 12 weeks. Lesion counts, Investigator's Static Global Assessments (ISGA), and Subject's Global Assessments (SGA) were evaluated at baseline and weeks 2, 4, 8, and 12. Tolerability was monitored throughout the study. RESULTS: At week 12 in both studies, treatment with tazarotene foam led to greater decreases from baseline in mean absolute and percentage change in lesion counts (noninflammatory, inflammatory, and total), greater proportion of participants with ≥2-grade improvement in ISGA score, and greater proportion of participants with ISGA score of 0 or 1 than vehicle treatment (P<.001 for all). Only application-site skin irritation and dryness were reported by >5% of participants in active treatment groups in both studies. LIMITATIONS: The efficacy and tolerability of tazarotene foam were not compared directly with those of other formulations. CONCLUSION: Tazarotene foam, 0.1% significantly reduced the number and severity of acne lesions after 12 weeks and had a safe and acceptable tolerability profile.

Safety and efficacy of clindamycin phosphate 1.2%-benzoyl peroxide 3% fixed-dose combination gel for the treatment of acne vulgaris: a phase 3, multicenter, randomized, double-blind, active- and vehicle-controlled study.

BACKGROUND: Topical fixed-combination therapy containing 1% clindamycin as 1.2% clindamycin phosphate (CLNP) and 3% benzoyl peroxide (BPO) is an effective treatment for acne vulgaris (acne). OBJECTIVES: To demonstrate that the combination of 1.2% CLNP with lower strength BPO (CLNP 1.2%-BPO 3%) in a gel formulation is superior to each individual ingredient, CLNP 1.2% and BPO 3%, and vehicle gel. METHODS: A total of 1,319 patients with acne, aged 12 years or older, were enrolled and randomized (1:1:1:1) to receive CLNP 1.2%-BPO 3%, CLNP 1.2% gel, BPO 3% gel, or vehicle gel once-daily in a 12-week, multicenter, double-blind, parallel-group, vehicle-controlled study. Subjects were evaluated at baseline, weeks 2, 4, 8, and 12 or early termination. Assessment of efficacy was evaluated using a six-point Investigator's Static Global Assessment (ISGA) and Subject's Global Assessment (SGA) of acne severity and lesion counts (inflammatory, non-inflammatory, and total). Safety assessments included skin tolerability and adverse events (AEs). RESULTS: A greater proportion of subjects who used CLNP 1.2%-BPO 3% gel (39%) had a two grade improvement in ISGA from baseline to week 12 compared with CLNP 1.2% (25%; P<0.001), BPO 3% (30%; P=0.016), and vehicle (18%; P<0.001). CLNP 1.2%- BPO 3% was superior to CLNP 1.2% and vehicle alone in the absolute reduction from baseline to week 12 in all three lesion types (P<0.001 all pair-wise comparisons). CLNP 1.2%-BPO 3% was superior to BPO 3% alone in the absolute reduction from baseline to week 12 in inflammatory (P=0.015) and total (P=0.032) lesion counts. The incidence of product-related AEs was low and similar in all study groups (1% with CLNP 1.2%-BPO 3%, 2% with CLNP 1.2%, 2% with BPO 3%, and 2% with vehicle). Local tolerability assessments showed similar minimal changes from baseline to week 12 in all study groups. CONCLUSION: CLNP 1.2%-BPO 3% gel provides superior efficacy to improve ISGA score and reduce inflammatory and total lesion counts compared with the individual active ingredients (CLNP 1.2% and BPO 3%) and vehicle, while maintaining a highly favorable safety and tolerability profile similar to BPO 3% alone.

Randomized tolerability analysis of clindamycin phosphate 1.2%-tretinoin 0.025% gel used with benzoyl peroxide wash 4% for acne vulgaris.

The multiple etiologic factors involved in acne vulgaris make the use of several medications necessary to treat the condition. Use of a fixed combination of clindamycin phosphate 1.2% and tretinoin 0.025% in conjunction with a benzoyl peroxide (BPO) wash 4% targets several pathologic factors simultaneously and mitigates the potential for clindamycin-induced Propionibacterium acnes-resistant strains. New formulations may allow such regimens to be effectively used without overly reduced tolerability resulting from the irritation potential of tretinoin and BPO. This randomized, single-blind study investigated the local tolerability, irritation potential, and safety of an aqueous-based gel (clindamycin phosphate 7.2%-tretinoin 0.025% [CT gel]) when used in conjunction with a BPO wash 4% in participants with mild to moderate acne vulgaris. Participants applied the CT gel once daily in the evening for 4 weeks in conjunction with once-daily morning use of either BPO wash 4% or nonmedicated soap-free cleanser lotion (SFC). Local tolerability and irritation potential were assessed by participants and investigators using separate 6-point scales. The frequency and severity of dryness, scaling, erythema, burning/stinging, and itching increased during the first week of treatment in both treatment arms but decreased thereafter. Local tolerability reactions were slightly more frequent in the CT gel + BPO wash group versus the CT gel + SFC group at week 1 but were generally mild and improved within 1 to 2 weeks. In conclusion, therapy with CT gel + BPO wash appears safe and well-tolerated in participants with mild to moderate acne vulgaris.

Clinical Pharmacology and Safety of Trifarotene, a First-in-Class RARγ-Selective Topical Retinoid.

Trifarotene is a new drug with retinoic acid receptor activity and selectivity for retinoic acid receptor-γ. The reported studies aimed at assessing the clinical pharmacology and safety of trifarotene. The clinical pharmacology of topical trifarotene up to 100 µg/g was extensively investigated through 2 maximal usage pharmacokinetic trials (MUsT) conducted in adult (≥18 years) and pediatric patients (9-17 years) with moderate to severe acne and two studies conducted in healthy volunteers: 1 thorough QTC study and 1 drug-drug interaction study with concomitantly administered oral levonorgestrel (0.15 mg)/ethinyl estradiol (0.03 mg). Safety assessments included adverse event reporting and assessment of erythema, scaling, dryness, and stinging/burning using a scale from 0 = none to 4 = severe, as well as the evaluation of the systemic safety of trifarotene through routine laboratory testing. Systemic absorption of trifarotene was generally unquantifiable in the target population, especially when applied at 50 µg/g. QTC investigations did not show any risk of cardiovascular health issues; trifarotene did not reduce the systemic exposure to oral contraceptives such as levonorgestrel/ethinyl estradiol. Safety analyses did not show local or systemic safety concerns with trifarotene up 100 µg/g, a dose twice as high as the intended market dose. Results showed that trifarotene 50 µg/g cream is well tolerated and safe, even when applied under maximized conditions in adults and pediatric acne patients presenting with severe acne. Daily use of trifarotene 50 µg/g cream was not associated with cardiovascular effects and did not result in drug-drug interaction in women of childbearing potential using oral contraception.

5% 5-Fluorouracil cream for treatment of verruca vulgaris in children.

Warts are a common pediatric skin disease. Most treatments show only modest benefit, and some are poorly tolerated because of pain. 5-fluorouracil interferes with deoxyribonucleic acid and ribonucleic acid synthesis, and is used to treat genital warts in adults. Efficacy, safety, and tolerability of topical 5% 5-fluorouracil for treatment of common warts were examined in an open-label pilot study with pediatric patients. Thirty-nine children who have at least two hand warts applied 5% 5-fluorouracil cream (Efudex, Valeant Pharmaceuticals International) once or twice daily, under occlusion for 6 weeks. Assessment of treatment response and side effects was performed at baseline, treatment completion, and 3- and 6-month follow-ups. Hematology measures, liver function tests, and medication blood levels were reassessed at treatment completion. Eighty-eight percent of treated warts improved after 6 weeks of treatment, and 41% of subjects had complete resolution of at least one wart. Treatment response did not differ between once or twice daily applications. Tolerability and patient satisfaction were excellent. No subject had clinically significant blood levels of 5-fluorouracil. At 6 month follow-up, 87% of complete responders had no wart recurrence. Topical 5% 5-fluorouracil is a safe, effective, and well-tolerated treatment for warts in children.

Is benzoyl peroxide 3% topical gel effective and safe in the treatment of acne vulgaris in Japanese patients? A multicenter, randomized, double-blind, vehicle-controlled, parallel-group study.

Benzoyl peroxide (BPO) as an anti-acne medication is not yet approved in Japan. This study evaluated the efficacy and safety of a once-daily topical application of BPO 3% gel versus an inert vehicle gel in Japanese acne patients. Three hundred and sixty patients were randomized to receive BPO 3% or vehicle for 12 weeks. The primary efficacy end-point was absolute change in number of total lesions (TL) from baseline to week 12 to demonstrate the superiority of BPO 3% versus vehicle. Secondary efficacy end-points were absolute and percent change in TL, inflammatory lesions (IL), non-inflammatory lesions (non-IL) and Investigator's Static Global Assessment (ISGA). Change in TL counts from baseline to week 12 for BPO 3% was superior to vehicle (difference, -21.0; P < 0.001). Absolute and percent reductions in TL, IL and non-IL counts were greater for BPO 3% at all study visits. The proportion of patients with improvement in ISGA scores was significantly higher with BPO 3% than with vehicle from week 2. All adverse events were mild or moderate. Adverse drug-related reactions were higher for BPO 3% (30%) than with vehicle (5%). Local tolerability scores of grade 1 or more (slight to moderate) were more frequent with BPO 3% than vehicle with the most significant differences observed in dryness (56% vs 27% at week 1-4), peeling (19% vs 9% at week 1-2) and burning/stinging (58% vs 15% at week 1-12). These results indicate that BPO 3% is effective while maintaining a favorable safety and tolerability profile in Japanese acne patients.

Tazarotene foam versus tazarotene gel: a randomized relative bioavailability study in acne vulgaris.

BACKGROUND AND OBJECTIVE: Tazarotene, a retinoid pro-drug, is available in gel, cream and foam for the topical treatment of acne vulgaris. This single-centre, randomized, open-label study assessed relative bioavailability of its active metabolite tazarotenic acid after dosing of tazarotene foam or gel. STUDY DESIGN AND METHODS: Subjects with moderate-to-severe acne received a mean, once-daily dose of 3.7 g tazarotene foam or gel applied to face, chest, upper back and shoulders. Blood samples were collected pre-dose on multiple days and multiple time points over a 72-h period to measure plasma tazarotenic acid and tazarotene. RESULTS: Mean tazarotenic acid area under the plasma concentration-time curve (AUC) and maximum measured plasma concentration (Cmax) values were significantly higher for gel versus foam. Cmax occurred within 5-6 h after dosing, with an apparent terminal elimination half-life (t½) of 18-22 h. Accumulation was observed upon repeated dosing with steady-state conditions achieved at day 20. Mean tazarotene concentrations were also higher following gel application versus foam. Both foam and gel demonstrated an acceptable safety profile. CONCLUSION: Tazarotene foam, 0.1 % is an alternative to gel with less systemic exposure.

Bioavailability of Clindamycin From a New Clindamycin Phosphate 1.2%-Benzoyl Peroxide 3% Combination Gel.

A new topical fixed-dose combination product containing clindamycin (1%, formulated as 1.2% clindamycin phosphate, CLNP 1.2%) with low strength (3%) benzoyl peroxide (BPO) in a methylparaben-free gel vehicle (CLNP 1.2%-BPO 3%-MPF) has been developed for the treatment of acne. The objective of this study was to determine the relative bioavailability of clindamycin and clindamycin sulfoxide from CLNP 1.2%-BPO 3%-MPF compared with clindamycin phosphate 1.2%-BPO 5% in a methylparaben-preserved gel vehicle (CLNP 1.2%-BPO 5%-MP) and clindamycin phosphate 1.2%-BPO 5% in a methylparaben-free gel vehicle (CLNP 1.2%-BPO 5%-MPF), and to determine whether exposure is affected by BPO concentration (3% vs. 5%) when applied topically. Seventy-two subjects with moderate-severe acne were randomized to receive CLNP 1.2%-BPO 3%-MPF, CLNP 1.2%-BPO 5%-MP, or CLNP 1.2%-BPO 5%-MPF in a 5-day, open-label, and parallel-group study. Cmax and AUC values for clindamycin were highest for CLNP 1.2%-BPO 5%-MP, followed by CLNP 1.2%-BPO 3%-MPF and CLNP 1.2%-BPO 5%-MPF, but differences were not statistically significant. Systemic exposure to clindamycin and clindamycin sulfoxide was low and comparable between the formulations. Results indicate that differences in BPO concentration do not influence clindamycin bioavailability.

Evaluación diagnóstica psicológica sobre hipoglicemia en pacientes diabéticos con insulinoterapia / Psychological diagnosis evaluation hipoglycaemia in diabetic patients with insulinotherapy prospective study with 57 patients

La hipoglicemia es la complicación más frecuente del diabético en tratamiento insulínico. Persuadidos del deterioro progresivo de la integridad del sistema contrarregulador ante la hipoglicemia del paciente diabético, se correlacionó su comportamiento y grado de preocupación mediante el método de encuestas del Dr. Cox D., modificado, con el control de sus glicemias mensuales y hemoglobinas glicosiladas trimestrales durante 9 meses a 57 pacientes pertenecientes a la Unidad de Diabetes del Hospital Vargas de Caracas. La mayoría de nuestros pacientes demostraron estar moderadamente preocupados ante el riesgo de tener hipoglicemia con mal control; esto quizá asociado a que las complicaciones debidas a la hiperglicemia son percibidos por ellos como más deteriorantes e incapacitantes, pudiendo resolver el evento de hipoglicemia por ellos mismos mediante la ingesta de azúcares sin el control médico inmediato. Es necesario insistir en estrategias de Educación Continua al paciente diabético y a sus familiares, mediante un equipo de salud multidisciplinario, creando programas de acción social a fin de hacer eficientes los esfuerzos invertidos. De lo contrario, nuestros pacientes diabéticos llegarán a un avanzado estado de deterioro físico y psicológico, lo cual generaría mayores gastos para el Estado en su manutención, hospitalización y tratamiento