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In this trial, patients with secondary hyperparathyroidism who were undergoing dialysis were assigned to receive either the calcimimetic agent cinacalcet or placebo. Cinacalcet did not significantly reduce the risk of death or major cardiovascular events. Cardiovascular disease is very common among patients with chronic kidney disease, including those treated with hemodialysis, among whom the risk of death from cardiovascular disease is increased by a factor of 10 or more as compared with the risk in the general population. 1 , 2 Cardiovascular risk factors that have been linked to chronic kidney disease include heightened states of inflammation, 3 oxidative stress, 4 activation of the renin–angiotensin–aldosterone system 5 and the sympathetic nervous system, 6 endothelial dysfunction, 7 retention of uremic toxins promoting atherosclerosis and arteriosclerosis, 8 abnormalities in platelet aggregation, 9 anemia, 10 and disorders of bone and mineral metabolism, including hyperphosphatemia, hypercalcemia, and secondary hyperparathyroidism. . . .

Adapalene is used for treatment of acne vulgaris, a common dermatological disease. Nano-based carriers have been developed to improve solubility and bioavailability of adapalene and other acne treatment drugs. In our previous report, tea tree oil nanoemulsion containing adapalene gel (TTO NE + ADA Gel) showed appropriate physical and biological properties such as stability, viscosity, pH, size, morphology and biocompatibility in an animal model. The present study was designed to assess efficacy and safety of the TTO NE + ADA Gel in comparison with 0.1% adapalene marketed gel (ADA Marketed Gel). A total of 100 patients were randomized to receive TTO NE + ADA Gel or ADA Marketed Gel, once daily at night, for 12 weeks. Analysis for efficacy was conducted by acne lesion count (total, inflammatory and non-inflammatory) and acne severity index at weeks 4, 8 and 12 using generalized estimating equation along with the safety assessments in each measurement for assessing dryness, erythema, burning sensation and irritation. Significantly better reduction in total, inflammatory, and non-inflammatory acne lesions were reported for TTO NE + ADA Gel as compared to the ADA Marketed Gel overall and on each measurement occasion ( p value  < 0.001 for all). Mean acne severity index also reduced with TTO NE + ADA Gel significantly in comparison with ADA Marketed Gel ( p value  < 0.001). Dryness was the most common adverse effect reported in both groups and it was higher in TTO NE + ADA Gel group. In conclusion, TTO NE + ADA Gel compared to ADA Marketed Gel appears more effective in the treatment of acne vulgaris, with no important change in adverse effects.

Background Premature ejaculation (PE) is a prevalent male sexual dysfunction with limited comparative data on pharmacological treatments. This randomized clinical trial aimed to evaluate the efficacy and safety of four active pharmacological interventions for lifelong PE. Methods A prospective randomized trial was conducted from June 2024 to March 2025 at Beni-Suef University Hospital. Four hundred eligible patients diagnosed with lifelong PE were randomly allocated to one of four active treatment groups ( n  = 100 per group): (1) citalopram 20 mg/day, (2) silodosin 4 mg/day, (3) dapoxetine 30 mg on-demand (1–3 h before intercourse), or (4) dapoxetine 30 mg daily. The primary outcome was the change in intravaginal ejaculatory latency time (IELT) measured by stopwatch. Secondary outcomes included changes in the Premature Ejaculation Profile Questionnaire (PEPQ) scores and the incidence of treatment-emergent adverse events. Statistical analysis was performed using ANOVA with post-hoc tests for continuous variables and chi-square tests for categorical data. Results All four treatment groups demonstrated significant within-group improvements in IELT from baseline ( p  < 0.001 for all). The citalopram group exhibited the greatest mean IELT increase (from 110.4 ± 31.5s to 391.2 ± 45.9s; 260% median gain), outperforming the daily dapoxetine (220%), on-demand dapoxetine (197%), and silodosin (149.5%) groups. Improvements in PEPQ scores mirrored the IELT findings, with citalopram showing a 300% improvement compared to 225%, 166.7%, and 175% in the daily dapoxetine, on-demand dapoxetine, and silodosin groups, respectively. In inter-group comparisons, citalopram was superior to silodosin in all PEPQ domains ( p  < 0.001) and to both dapoxetine regimens in the domain of interpersonal difficulty ( p  < 0.01). Adverse event profiles differed: silodosin was associated with a higher incidence of ejaculatory dysfunction (23% retrograde ejaculation), while daily dapoxetine led to more systemic effects (18% dizziness). Conclusion In this direct head-to-head comparison of active treatments for lifelong PE, daily citalopram (20 mg) demonstrated superior efficacy in prolonging IELT and improving psychosocial outcomes compared to daily or on-demand dapoxetine and silodosin. The findings suggest that citalopram is a highly effective first-line option, while the dose-dependent efficacy of dapoxetine and the distinct side-effect profile of silodosin provide alternative considerations for personalized treatment strategies. Trial registration This clinical trial was registered at ClinicalTrials.gov (Identifier NCT07113145) on 7 August 2025 after the enrollment of the first participant and is therefore retrospectively registered.”

To evaluate the effectiveness of non-aromatic very rich in steranes (NAVS) naphthalan in the treatment of oral lichen planus (OLP) and recurrent aphthous stomatitis (RAS). Null hypothesis was that there would be no difference between NAVS and topical steroids in the treatment of OLP and RAS. The study consisted of two sub-trials conducted as randomized, double-blind controlled studies: first included OLP patients and second patients with RAS. Patients received either NAVS or 0.05% betamethasone dipropionate. Primary outcomes were activity score (OLP patients), No of lesions and lesion diameter (RAS patients) and pain intensity (VAS) while secondary outcome included the impact of the disease on quality of life assessed by Oral health impact profile (OHIP 14). No significant differences in terms of OLP clinical signs (p = 0.84, η2 = 0.001) and responses on the OHIP-14 (p = 0.81, η2 = 0.002) or on VAS (p = 0.14, η2 = 0.079) between NAVS and betamethasone groups were observed. In RAS patients, no significant differences between the groups in terms of lesion number (at days 3 and 5, p = 0.33 and p = 0.98, respectively), lesion diameter (days 3 and 5, p = 0.24 and p = 0.84, respectively) were observed. However, in NAVS group a significant reduction of lesions diameter was observed on the 3rd day, while in betamethasone group a significant reduction in lesions diameter was evident only after the 5th day. No significant differences in VAS (p > 0.05) and the OHIP-14 (p > 0.05) between groups were found. No evidence of differences between the two compared interventions was found. Retrospective registration of this trial was conducted in ClinicalTrials.gov on September 30, 2016; trial registration number: NCT02920658. https://clinicaltrials.gov/ct2/show/NCT02920658?term=NAVS&draw=2&rank=4.

Achieving NKF-K/DOQI™ bone metabolism and disease treatment goals with cinacalcet HCl. The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI™) has established guidelines for treatment of secondary hyperparathyroidism (HPT). The ability of cinacalcet HCl (Sensipar™) treatment to improve achievement of target levels of parathyroid hormone (PTH), calcium, phosphorus, and calcium-phosphorus product (Ca × P) was investigated in subjects on dialysis with secondary HPT. Data were combined from three placebo-controlled, double-blind, 26-week studies with similar design that randomized 1136 subjects on dialysis to receive traditional therapy plus cinacalcet or placebo. Oral cinacalcet was titrated from 30 to 180mg/day. Achievement of K/DOQI goals was determined for each treatment group overall and for subgroups defined by baseline intact PTH (iPTH) and Ca × P levels. Cinacalcet-treated subjects were more likely to achieve a mean iPTH ≤300 pg/mL (31.8 pmol/L) than were control subjects on traditional therapy (56% vs. 10%, P < 0.001). Cinacalcet-treated subjects were more likely to achieve concentrations of serum calcium within 8.4 to 9.5mg/dL (2.10–2.37mmol/L) and serum phosphorus within 3.5 to 5.5mg/dL (1.13–1.78mmol/L) than were control subjects (49% vs. 24% and 46% vs. 33%, P < 0.001 for each). Cinacalcet also improved achievement of Ca × P < 55mg2/dL2 (4.44mmol2/L2) and concurrent achievement of Ca × P < 55mg2/dL2 (4.44mmol2/L2) and iPTH ≤300 pg/mL (31.8 pmol/L) (65% vs. 36% and 41% vs. 6%, P < 0.001 for each). In subjects on dialysis with secondary HPT, cinacalcet facilitates achievement of the K/DOQI-recommended targets for PTH, calcium, phosphorus, and Ca × P.

Verinurad is a selective inhibitor of uric acid transporter 1 (URAT1). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of verinurad + allopurinol and verinurad monotherapy in healthy participants. Studies 1 (NCT03836599) and 2 (NCT02608710) were randomized Phase 1 studies. In Study 1, 12 healthy Asian participants received 24 mg verinurad + 300 mg allopurinol or placebo, and 9 healthy Chinese participants received 12 mg verinurad + 300 mg allopurinol. In Study 2, 24 healthy non‐Asian male participants received 12 mg verinurad. Safety analyses included assessment of adverse events (AEs). Pharmacokinetic parameters included maximum concentration (Cmax) and area under plasma concentration‐time curve (AUC) over 24 h (AUCτ). Pharmacodynamic parameters included percentage change from baseline (day –1) in serum uric acid (sUA) and urinary uric acid (uUA). There were no serious AEs or deaths in either study. In Study 1, steady‐state geometric mean (gCV%) Cmax and AUCτ values of verinurad after 7 days’ dosing were 73.6 (29.0) ng/mL and 478 (18.4) ng·h/mL, respectively, in healthy Asian participants, and 42.0 (40.1) ng/mL and 264 (36.1) ng·h/mL, respectively, in healthy Chinese participants; in Study 2, gCV% values were 36.3 (36.5) ng/mL and 271 (31.0) ng·h/mL, respectively. sUA decreased and uUA excretion increased compared with baseline following verinurad + allopurinol (Study 1) or verinurad (Study 2). When accounting for dose, the steady‐state pharmacokinetics of verinurad following multiple dosing were comparable between healthy Asian and Chinese participants and healthy non‐Asian participants. Verinurad treatments were well tolerated, including at higher verinurad exposures than previously evaluated after repeated dosing.

Itraconazole is currently used for the treatment of cutaneous sporotrichosis. Terbinafine at a daily dose of 250 mg has been successfully applied to the treatment of cutaneous sporotrichosis. Objective To compare the efficacy of 250 mg/day terbinafine and 100 mg/day itraconazole for the treatment of cutaneous sporotrichosis. Materials and methods A bidirectional cohort study was conducted on 55 patients receiving 250 mg/day terbinafine and 249 patients receiving 100 mg/day itraconazole. The latter patients were matched for age and clinical form to the terbinafine group at a ratio of 5:1. Sporothrix schenckii was isolated by culture from all patients (age range: 18–70 years), who were submitted to the standard care protocol consisting of clinical and laboratory evaluation and periodic visits. Results Cure was observed in 51 (92.7%) patients of the terbinafine group and 229 (92%) of the itraconazole group within a similar mean period of time (11.5 and 11.8 weeks, respectively). An increase in the terbinafine dose to 500 mg was necessary in two patients due to the lack of a response, and one patient presented recurrence. In the itraconazole group, two patients required a dose increase and three presented recurrence. Adverse events were equally frequent among patients receiving terbinafine ( n  = 4, 7.3%) and itraconazole ( n  = 19, 7.6%) and were generally mild without the need for drug discontinuation, except for two patients of the itraconazole group. Conclusion Terbinafine administered at a daily dose of 250 mg is an effective and well-tolerated option for the treatment of cutaneous sporotrichosis.

Summary Introduction Suppressing both androgens and estrogens may circumvent hormone receptor resistance in breast cancer by reducing androgen receptor stimulation. Selective inhibition of the 17, 20-lyase enzyme by orteronel leads to decreased androgen production in men and would be anticipated to reduce estrogen and androgen production in women. Thus, we conducted a phase 1b study of orteronel in postmenopausal women with hormone-receptor positive (HR+) metastatic breast cancer. Methods The primary objective was to identify the recommended phase 2 dose (R2PD) of orteronel in women; escalation was via standard 3 + 3 design. The initial dose was 300 mg BID and escalated to 400 mg BID. Cycle length was 28 days. Enrolled patients had HR+ metastatic breast cancer and were evaluated every 8 weeks for disease progression. Results Eight heavily pre-treated women enrolled [median age: 57 yo (range 47–73)]. Four received 300 mg BID at dose level 1; 4 received 400 mg BID at dose level 2. No dose limiting toxicities (DLTs) were observed. Adverse events (AE) at least possibly related to orteronel included grade 1–2 nausea ( n  = 4) and bone pain ( n  = 3), and grade 1 hypokalemia, hot flashes, myalgia and AST elevation ( n  = 2). The only grade 3 AE was hypertension ( n  = 2) with 8 patients receiving 34 cycles of treatment. No objective responses were seen; clinical benefit was seen in 2 patients with stable disease for more than 6 months. Serum estrogens and testosterone were suppressed from baseline on both doses of orteronel. Conclusions Orteronel 400 mg BID is well tolerated in postmenopausal women, and significantly suppresses serum estrogens and testosterone. Clinical benefit was seen among heavily pretreated postmenopausal women with HR+ metastatic breast cancer.

Verinurad (RDEA3170) is a selective uric acid reabsorption inhibitor in clinical development for treatment of gout and asymptomatic hyperuricemia. This study evaluated verinurad pharmacokinetics, pharmacodynamics, and tolerability in healthy Japanese and non-Asian adult male subjects. This was a Phase I, randomized, single-blind, placebo-controlled study. Panels of 8 Japanese subjects were randomized to receive oral verinurad (2.5-15 mg) or placebo administered as a single dose in a fasted and fed state and as once-daily doses for 7 days in a fed state. Eight non-Asian subjects received verinurad 10 mg as a single dose (fasted and fed) and multiple doses in the fed state. Serial plasma/serum and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse events and laboratory data. Of 48 randomized subjects, 46 (Japanese, 39; non-Asian, 7) completed the study. Following single or multiple doses in Japanese subjects, maximum plasma concentration ( ) and area under the plasma concentration-time curve (AUC) increased in a near dose-proportional manner. Time to ( ) was ~1.25-2.0 hours with fasting. A moderate-fat meal delayed (range 3.0-5.0 hours) and had a variable effect on AUC (0%-97% increase) and (0%-26% increase) across the dose groups. Following multiple verinurad 10 mg doses, and AUC were 38% and 23% higher, respectively, in Japanese vs non-Asian subjects, largely due to body weight differences. Mean reduction of serum urate following multiple verinurad 10 mg doses was 46% and 44% after 24 hours in Japanese and non-Asian subjects, respectively. Verinurad was well tolerated at all doses. Verinurad monotherapy lowered serum urate and was well tolerated in both healthy Japanese and non-Asian males, while small differences in plasma pharmacokinetics were observed. These data support further evaluation of once-daily verinurad as a treatment for gout and asymptomatic hyperuricemia.

The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. A need exists for a therapy that lowers parathyroid hormone (PTH) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism. The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium, thereby reducing PTH secretion. Consequently, AMG 073 may provide a novel therapy for secondary hyperparathyroidism. Seventy-eight hemodialysis patients with secondary hyperparathyroidism were enrolled into this 18-week, double-blind, randomized, placebo-controlled, dose titration study. Daily oral AMG 073 doses were administered to determine the effect on PTH, serum calcium, phosphorus, and calcium x phosphorus. The mean baseline PTH was similar in patients administered AMG 073 or placebo (632 ± 280.1 pg/mL vs. 637 ± 455.9 pg/mL, respectively). PTH decreased by 26.0% in the AMG 073-treated group, compared with an increase of 22.0% in the placebo group (P < 0.001). A greater proportion in the AMG 073 group (38%) had a decrease in PTH ≥30%, compared with the placebo group (8%) (P = 0.001). Decreases in PTH were independent of baseline vitamin D usage. Patients receiving AMG 073 had an 11.9% decrease in calcium x phosphorus compared with a 10.9% increase in the placebo group (P < 0.001). Use of vitamin D sterols, as well as both calcium and noncalcium-containing phosphate binders. were similar between treatment groups. Administration of AMG 073 was safe and well tolerated in this 18-week study. The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with secondary hyperparathyroidism.