Berdazimer gel for molluscum contagiosum: An integrated analysis of 3 randomized controlled trials.

BACKGROUND: An out-of-office therapeutic agent indicated for molluscum contagiosum is needed. OBJECTIVE: To assess the efficacy and safety of berdazimer gel, 10.3% (a topical, antiviral, nitric oxide-releasing medication) versus vehicle. METHODS: Berdazimer gel, 10.3% or vehicle was applied once daily to all molluscum contagiosum lesions for 12 weeks in patients ≥6 months with 3-70 mollusca. Efficacy assessment: complete lesion clearance and partial clearance at week 12. Safety and tolerability assessment: adverse events through week 24 and local skin reactions through week 12. RESULTS: There were 1598 patients enrolled (n = 917 berdazimer, n = 681 vehicle). Berdazimer was superior to vehicle at week 12 in complete clearance rates, 30.0% versus 19.8% (odds ratio, 1.75; 95% CI, 1.38-2.23, P < .001). Subgroup analyses of primary efficacy showed consistent favorable efficacy for berdazimer across most subgroups, including age, sex, baseline lesion count, and disease duration. Berdazimer provided favorable outcome for partial clearance. Application-site pain (18.7% vs 4.8% in berdazimer vs vehicle) and erythema (11.7% vs 1.3%), mostly mild to moderate, were the most common local skin reactions. LIMITATIONS: Berdazimer sodium in molluscum patients with lesions (B-SIMPLE) trials enrolled only US patients; no efficacy assessments beyond week 12. CONCLUSIONS: Berdazimer gel, 10.3% showed favorable efficacy and safety across subgroups.

Berdazimer gel for molluscum contagiosum in patients with atopic dermatitis.

OBJECTIVE: Controlling molluscum contagiosum (MC) infections is critical in atopic dermatitis (AD) management. This post hoc analysis assessed the efficacy and safety of berdazimer gel, 10.3% (topical, antiviral, nitric oxide-releasing medication) versus vehicle in MC patients with or without AD. METHODS: Three Phase 3, multicenter, randomized, double-blind, vehicle-controlled, parallel-group trials (B-SIMPLE[berdazimer sodium in molluscum patients with lesions]1, -2, -4) enrolled patients 6 months and older with 3-70 mollusca. Berdazimer or vehicle was applied once daily to all MC lesions for 12 weeks. Data from three Phase 3 studies were integrated for subgroup efficacy and safety assessments using several weighted meta-analysis approaches. Patients with concurrent AD or a history of AD/eczema were categorized as AD+ subgroup (AD- when absent). Primary efficacy endpoint: complete lesion clearance at Week 12. Safety endpoints included adverse events (AEs) through Week 24 and local skin reactions through Week 12. RESULTS: Of 1598 enrolled patients, 209 (13.1%) were AD+. Baseline mean lesion counts were greater in AD+ (26.4) than AD- (19.3). Complete clearance rates were higher at Week 12 for berdazimer compared with vehicle in AD+ (n = 209; 35.0% vs. 27.4%; odds ratio [OR], 1.3; 95% CI, 0.7-2.5) and AD- (n = 1389; 29.1% vs. 18.9%; OR 1.8; 95% CI 1.4-2.4) subgroups. AEs in AD+ were application-site pain (21.6% with berdazimer vs. 11.9% with vehicle), dermatitis (12.8% vs. 2.4%), and erythema (9.6% vs. 7.1%). CONCLUSIONS: Berdazimer gel showed favorable efficacy regardless of AD status. Berdazimer-induced erythema may be indistinguishable from AD symptoms or with inflammatory response upon resolution of molluscum.

Pharmacokinetic Profile, Safety, and Tolerability of Topical Berdazimer Gel, 10.3% in Patients With Molluscum Contagiosum.

BACKGROUND: Berdazimer (SB206), gel 10.3% is a novel, topical, nitric oxide–releasing agent intended for molluscum contagiosum (MC) treatment. METHODS: A 12-week, open-label, multicenter trial evaluated the safety, tolerability, and pharmacokinetic (PK) parameters of berdazimer gel, 10.3% applied topically once daily for the treatment of MC. Patients were aged ≥6 months with >20 molluscum lesions. The primary endpoint was the PK profile of the hydrolyzed N-methylaminopropyl-trimethoxysilane (hMAP3) monomer and nitrate during a 2-week period of once-daily berdazimer gel, 10.3% application (PK period) under maximal use conditions. Safety and tolerability were evaluated throughout the 12-week study period. RESULTS: Half of the 34 enrolled patients (17) were female and most (97.1% [33/34]) were white. Patients were 2 to 12 years old (mean, 5.3 years) with a mean of 50 MC lesions at baseline (mean time since MC awareness, 12.4 months). No patients had quantifiable plasma hMAP3 concentrations on day 1. On day 15, 2 patients had quantifiable plasma hMAP3 concentrations; however, the maximum concentration (33.9 ng/mL) was >10-fold lower than the no observed adverse effect level (NOAEL) in an animal toxicology study. Mean nitrate concentration–time profiles were similar on days 1 and 15 and remained flat for all patients throughout the 2-week PK period. The highest plasma methemoglobin level observed was 3.2%. Application-site pain (13/34 [38.2%]) and application-site erythema (6/34 [17.6%]) were the most frequent treatment-emergent adverse events (TEAEs), and most TEAEs were mild or moderate. CONCLUSIONS: Once-daily berdazimer gel, 10.3% was well-tolerated with minimal systemic absorption. J Drugs Dermatol. 2022;21(10):1104-1110. doi:10.36849/JDD.6938.

Safety of Lubiprostone in Pediatric Patients With Functional Constipation: A Nonrandomized, Open-Label Trial.

OBJECTIVES: Pediatric functional constipation (PFC) affects up to 30% of children. Current treatments often do not sustain symptomatic relief. Lubiprostone is a locally acting chloride channel activator that promotes fluid secretion into the small bowel without affecting serum electrolyte concentrations. We assessed the safety/tolerability of oral lubiprostone as treatment for PFC in a 24-week study. METHODS: This phase 3 open-label safety trial conducted from April-November 2016 at 13 US sites included patients (ages 6-17 years) diagnosed with PFC (Rome III criteria). Patients <50 and ≥50 kg received lubiprostone 12 or 24 mcg twice daily, respectively, for 24 weeks. Safety endpoints included incidence of treatment-emergent adverse events (TEAEs) and changes from baseline in clinical laboratory parameters and vital signs. RESULTS: Overall, 87 patients receiving lubiprostone, 64.3% (36/56) in the 12-mcg group and 54.8% (17/31) in the 24-mcg group, completed the study. Of 12 TEAEs leading to discontinuation, only upper abdominal pain occurred in >1 patient. TEAEs were mostly mild in intensity, with gastrointestinal disorders (diarrhea, vomiting) most frequently reported. No safety concerns were found in vital signs, abbreviated physical examinations, and laboratory tests. Subgroup analyses assessed an impact of age, sex, and race categories on TEAEs and treatment-related adverse events. Mean investigators' assessments of treatment effectiveness (scale of 0-4) for lubiprostone 12- and 24-mcg groups, respectively, were 2.8 and 2.9 at week 12, and 2.7 and 2.2 at week 24. CONCLUSIONS: Lubiprostone was well tolerated in the pediatric population. The incidence of TEAEs was comparable to that observed in previous clinical trials and in adults.

Recent Developments and Advances in Atopic Dermatitis: A Focus on Epidemiology, Pathophysiology, and Treatment in the Pediatric Setting.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects a substantial number of children and has a significant negative impact on affected patients and their caregivers/families. Recent studies have led to significant evolutions in the understanding of AD pathogenesis, epidemiology, and treatment. The first point of contact for many patients with new-onset AD is usually with their primary care provider or pediatrician. This underscores the importance for pediatricians to understand the basic pathophysiology and current standards of care for AD. This article provides up-to-date information and reviews the basic principles of AD pathophysiology, diagnosis, and management. In addition, the article highlights recent advances in scientific research regarding the mechanisms involved in the pathogenesis of atopic dermatitis that have resulted in the discovery of novel therapeutic targets and the development of targeted biologic therapies with the potential to revolutionize AD therapy.