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Background: H 4 receptor antagonists are potential novel treatments for inflammatory skin diseases, including atopic dermatitis (AD)., Objective: We sought to study the efficacy and safety of ZPL-3893787 (a selective H 4 receptor antagonist) in patients with moderate-to-severe AD., Methods: A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate ZPL-3893787 (30 mg) once-daily oral therapy in adults with moderate-to-severe AD. Patients were randomized (2:1) to ZPL-3893787 (n = 65) or placebo (n = 33) for 8 weeks. Patients had a history of AD for more than 12 months, Eczema Area and Severity Index (EASI) scores of 12 or greater and 48 or less, Investigator's Global Assessment (IGA) scores of 3 or greater, pruritus scores of 5 or greater (0- to 10-point scale), and AD on 10% or greater of body surface area. Efficacy parameters included EASI, IGA, SCORAD, and pruritus assessment., Results: Treatment with oral ZPL-3893787 showed a 50% reduction in EASI score compared with 27% for placebo. The placebo-adjusted reduction in EASI score at week 8 was 5.1 (1-sided P = .01). Clear or almost-clear IGA scores were 18.5% with ZPL-3893787 versus 9.1% with placebo. SCORAD scores exhibited 41% reduction with ZPL-3893787 versus 26% with placebo (placebo-adjusted reduction of 10.0, P = .004). There was a 3-point reduction (scale, 1-10) in pruritus with ZPL-3893787, but there was a similar reduction with placebo, resulting in a nonsignificant difference (P = .249). Patient-reported pruritus subscores obtained from SCORAD were reduced with ZPL-3893787 compared with placebo at week 8 (nonsignificant). ZPL-3893787 was well tolerated., Conclusion: For the first time, these results showed that ZPL-3893787 improved inflammatory skin lesions in patients with AD, confirming H 4 receptor antagonism as a novel therapeutic option., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Nitrates and nitrate-containing compounds are vasodilators used for the treatment of angina and heart failure. Phosphodiesterase type 5 inhibitors used for the treatment of erectile dysfunction are also vasodilators, and when taken together with nitrates, synergistic effects that enhance hypotensive effects may occur. Phosphodiesterase type 5 inhibitors are therefore contraindicated in patients taking organic nitrates., Methods and Results: A literature review was performed to provide a historical overview of different phosphodiesterase type 5 inhibitors and nitrates and their interaction. The pharmacologic characteristics of phosphodiesterase type 5 inhibitors and nitrates are reviewed, and clinical recommendations for treating cardiovascular disease in men taking phosphodiesterase type 5 inhibitors are discussed. Pharmacologic and adverse drug reactions between nitrates and phosphodiesterase type 5 inhibitors are dependent on many variables. Organic nitrates remain an absolute contraindication in men treated with phosphodiesterase type 5 inhibitors. In general, nitrates may be taken 24 hours after the last dose of short-acting phosphodiesterase type 5 inhibitors and 48 hours after the last dose of long-acting phosphodiesterase type 5 inhibitors., Conclusions: This literature review determined that the use of phosphodiesterase type 5 inhibitors with nitrates is a contraindication, with the duration between the last dose of phosphodiesterase inhibitor and nitrate use generally varying between short- and long-acting phosphodiesterase type 5 formulations. Patients receiving nitrates who wish to use phosphodiesterase type 5 inhibitors should be educated regarding the interaction and should be evaluated to determine whether nitrate treatment can be discontinued. Further research is needed to determine how soon phosphodiesterase type 5 inhibitors can be restarted after a patient has taken a nitrate and the effect of high and low phosphodiesterase type 5 inhibitor doses on the interaction effect.

Objective: To investigate the efficacy and safety of repeated 12-week courses of 5 or 10 mg daily of ulipristal acetate for intermittent treatment of symptomatic uterine fibroids., Design: Double-blind, randomized administration of two 12-week courses of ulipristal acetate., Setting: Gynecology centers., Patient(s): A total of 451 patients with symptomatic uterine fibroid(s) and heavy bleeding., Intervention(s): Two repeated 12-week treatment courses of daily 5 or 10 mg of ulipristal acetate., Main Outcome Measure(s): Amenorrhea, controlled bleeding, fibroid volume, quality of life (QoL), pain., Result(s): In the 5- and 10-mg treatment groups (62% and 73% of patients, respectively) achieved amenorrhea during both treatment courses. Proportions of patients achieving controlled bleeding during two treatment courses were >80%. Menstruation resumed after each treatment course and was diminished compared with baseline. After the second treatment course, median reductions from baseline in fibroid volume were 54% and 58% for the patients receiving 5 and 10 mg of ulipristal acetate, respectively. Pain and QoL improved in both groups. Ulipristal acetate was well tolerated with less than 5% of patients discontinuing treatment due to adverse events., Conclusion(s): Repeated 12-week courses of daily oral ulipristal acetate (5 and 10 mg) effectively control bleeding and pain, reduce fibroid volume, and restore QoL in patients with symptomatic fibroids., Clinical Trial Registration Number: NCT01629563 (PEARL IV)., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)