A phase III, 52-week, open-label study to evaluate the safety and efficacy of 5% sofpironium bromide (BBI-4000) gel in Japanese patients with primary axillary hyperhidrosis.

A long-term study was conducted in Japanese patients with primary axillary hyperhidrosis who completed the preceding 6-week phase III, confirmatory study of 5% sofpironium bromide gel (hereinafter referred to as sofpironium) to evaluate the safety and efficacy of 52-week treatment with sofpironium. In the long-term study, 185 patients who completed the confirmatory study (94 and 91 patients in the vehicle and sofpironium groups, respectively) started to receive sofpironium (switching and extension groups, respectively), and all these patients were included in both the full analysis set (FAS) and the safety analysis set (SAF). In the FAS, there were more females than males (73.0% vs. 27.0%), and median age was 38.0 years. A total of 161 patients (86 and 75 patients in the switching and extension groups, respectively) completed the study at week 52. The proportions of patients with hyperhidrosis disease severity score of 1 or 2 and a 50% or more reduction in total gravimetric weight of sweat were 57.4% in the switching group and 58.2% in the extension group at week 52. The proportions of patients who achieved this efficacy end-point in the long-term study were similar to that (53.9%) in the sofpironium group in the confirmatory study. In the SAF, the incidences of adverse events (AEs) were 80.9% in the switching group and 83.5% in the extension group, and the incidences of adverse drug reactions were 39.4% and 45.1%, respectively. AEs that occurred in at least 20% of patients in both treatment groups were application site dermatitis (25.5% and 33.0%, respectively) and nasopharyngitis (31.9% and 23.1%, respectively). Reported AEs were generally mild, and there were no deaths. Serious AEs occurred in three patients, but none were considered related to the study drug. In this study, the efficacy of sofpironium was maintained during 52-week treatment, and no new safety risk was observed.

A phase 3, multicenter, randomized, double-blind, vehicle-controlled, parallel-group study of 5% sofpironium bromide (BBI-4000) gel in Japanese patients with primary axillary hyperhidrosis.

A phase 3 study was conducted to verify the efficacy and safety of 5% sofpironium bromide (BBI-4000) gel (hereinafter referred to as sofpironium) administrated for 6 weeks in Japanese patients with primary axillary hyperhidrosis. The primary efficacy end-point was the proportion of patients who satisfied both criteria of a Hyperhidrosis Disease Severity Score (HDSS) of 1 or 2 at the end of 6-week treatment and a 50% or more reduction in total gravimetric weight of sweat at the end of treatment relative to baseline. A total of 281 patients were randomized to receive 5% sofpironium (141 patients) or vehicle (140 patients), and all patients were included in the full analysis set (FAS). In the FAS, 70.1% of patients were female, and the median age was 35.0 years. The proportion of patients who achieved the primary efficacy end-point was 53.9% in the sofpironium group and 36.4% in the vehicle group, with a statistically significant difference of 17.5% (95% confidence interval, 6.02-28.93) between these two groups (P = 0.003). The incidence of adverse events was 44.0% in the sofpironium group and 30.7% in the vehicle group, and the incidence of adverse drug reactions was 16.3% in the sofpironium group and 5.0% in the vehicle group. Reported adverse events were generally mild or moderate in severity. In the sofpironium group, common events (incidence, ≥5%) were nasopharyngitis (14.2%) and dermatitis/erythema at the application site (8.5%/5.7%), with no serious adverse events reported. This study demonstrated the efficacy and safety of 5% sofpironium.

Antimalarial activity of 1-aryl-3,3-dialkyltriazenes.

The antimalarial activity of 1-aryl-3,3-dialkyltriazenes to Plasmodium berghei NK-65 in infected mice was evaluated at an intraperitoneal dose of 100mg/kgbw. Some of these compounds were found to possess potent antimalarial activity.

Tetrahydrobenzotriazines as a new class of nematocide.

Tetrahydrobenzotriazines, a novel class of heterocyclic compounds, were synthesized. Examination of their biological activities resulted in the discovery that some of them possess potent nematocidal activity.

Plucking during telogen induces apoptosis in the lower part of hair follicles.

Highly synchronized anagen development is achieved by depilation, which contrasts with spontaneous anagen development. The precise mechanism responsible for plucking-induced synchronization has not been explained. Plucking appears to mechanically injure or wound the follicle. We hypothesized that the injured hair follicle cells are removed by apoptosis, with an associated induction of synchronized anagen development. Female C57 BL/6 mice in which all the hair follicles of the back skin were in telogen were induced to enter anagen by depilation. Skin specimens from the back at 0 to 72 h after plucking were examined, and TUNEL staining and electrophoresis of isolated DNA were applied to substantiate the presence of apoptosis. Simultaneously, cell proliferation was also examined by bromodeoxyuridine (BrdU) incorporation. All methods of analysis revealed that plucking induced apoptosis of hair follicle cells in the dermal remnant, and there was a subsequent associated proliferative response that resulted in a highly synchronized anagen phase. From 12 to 36 h after plucking, hair follicle cells with weakly BrdU-positive nuclei were detected around the holes in the lower part of the follicle, which were induced by plucking. At 48 and 72 h, many cells with BrdU-positive nuclei were seen in the entire follicle, mainly in the bulb, as well as in the epidermis. Cell proliferation and apoptosis appeared to occur simultaneously after plucking. These findings mirror the events noted during the development of other organs in which the coordination of cell proliferation and apoptosis is essential for orderly restructuring events.