Ustekinumab 45 mg and 90 mg did not demonstrate meaningful efficacy in Japanese patients with severe AD. The treatment was generally well tolerated.

Tapentadol ER (25-200 mg bid) provides analgesic efficacy that is non-inferior to that provided by oxycodone HCl CR (5-40 mg bid) for the management of moderate to severe, chronic malignant tumor-related pain, and is well tolerated overall, with a better gastrointestinal tolerability profile than oxycodone CR.

Background and ObjectivesThe effectiveness and tolerability of tapentadol extended release (ER), a centrally acting analgesic with μ-opioid receptor agonist and norepinephrine (noradrenaline) reuptake inhibitor activities, have been demonstrated in patients with chronic pain, including those switching directly from prior opioid therapy. The objective of the current study was to evaluate the effectiveness and safety of conversion to oral tapentadol ER (50–250 mg twice daily) from previous around-the-clock strong opioid therapy in patients with moderate to severe, chronic malignant tumor–related cancer pain that was well-controlled.MethodsThis randomized, open-label, phase III study, which was conducted in Japan, included a 1- to 2-week screening period (on previous opioid) and an 8-week, open-label treatment period. Eligible patients, who were taking a strong opioid analgesic and had a mean pain intensity score <4 during the 3 days prior to randomization (adequate pain control on previous strong opioid), were randomized (1:1) to receive twice-daily treatment with tapentadol ER (100–500 mg/day) or morphine sustained release (SR; 20–140 mg/day; reference for assay sensitivity). Initial doses were estimated based on the conversion ratio of tapentadol ER:oxycodone:morphine:fentanyl = 10:2:3:0.03. The primary effectiveness endpoint was the proportion of patients who maintained pain control [change from baseline in mean pain intensity (11-point numerical rating scale) less than +1.5 for 3 consecutive days and no more than two doses of rescue medication per day for 3 consecutive days) during the first week of open-label treatment.ResultsIn the tapentadol ER group (n = 50), 84.0 % of patients (42/50; 95 % CI, 70.89–92.83) maintained pain control during Week 1. On the Patient Global Impression of Change, 2.1 % (1/48), 2.1 % (1/48), 22.9 % (11/48), and 50.0 % (24/48) of patients in the tapentadol ER group reported that their overall condition was “very much improved,” “much improved,” “minimally improved,” and “not changed,” respectively, at Week 1 compared with 0 %, 10.7 % (3/28), 28.6 % (8/28), and 53.6 % (15/28) reporting these ratings at Week 8. The sensitivity of effectiveness analyses was validated based on results using morphine SR; 98.0 % (49/50; 95 % CI, 89.35–99.95) of patients in the morphine SR group maintained pain control after 1 week of treatment. The overall safety profile was similar to that demonstrated in previous studies; tapentadol ER was associated with a lower incidence of gastrointestinal treatment-emergent adverse events than morphine SR [38.0 % (19/50) vs. 54.0 % (27/50)], including constipation [12.0 % (6/50) vs. 20.0 % (10/50)] and vomiting [6.0 % (3/50) vs. 26.0 % (13/50)].ConclusionsOverall, results indicate that conversion from previous strong opioids to tapentadol ER (50–250 mg twice daily) was successful and resulted in safe and effective pain control with improved gastrointestinal tolerability versus morphine SR in patients with moderate to severe cancer-related pain that was well-controlle...

Background A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC). Methods This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN (NCT01946204; patients with non-metastatic castration-resistant PC [nmCRPC]) and TITAN (NCT02489318; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 (NCT02162836; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio. Results Data from 68 patients (SPARTAN: n = 34, TITAN: n = 28, 56021927PCR1008: n = 6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36–1.81) and 1.0 month (IQR: 0.30–2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0–24 h) (AUC0–24, ss) at steady-state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without. Conclusions No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide-related skin rash is easily managed, with appropriate treatment with or without dose adjustment. Trial registration Retrospective pooled analysis of NCT01946204, NCT02489318, and NCT02162836.

ObjectiveAbiraterone acetate has been approved in >70 countries for chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naïve Japanese patients with metastatic castration-resistant prostate cancer was evaluated.MethodsMen, ≥20 years, with prostate-specific antigen levels of ≥5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy endpoint was proportion of patients achieving a prostate-specific antigen decline of ≥50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed.ResultsA confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was >35% (threshold response rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy endpoints: prostate-specific antigen response rate during treatment period: 62.5%; objective radiographic response, partial response: 4/18 (22.2%) patients; complete response: none; stable disease: 11/18 (61.1%) patients; median percent change in prostate-specific antigen level from baseline at Week 12: −66.62%. Median prostate-specific antigen response duration and progression-free survival were not reached, and median radiographic progression-free survival was 253 days. Of 31/48 (64.6%) patients experienced adverse events of special interest; most common was hepatic function abnormality (37.5%, Grade 3: 10.4%). One Grade 3 hypertension was the only mineralocorticoid adverse event >Grade 1/2.ConclusionsEfficacy of abiraterone acetate plus prednisolone was demonstrated by decline in prostate-specific antigen levels with evidence of antitumor activity by radiography in Japanese patients with chemotherapy-naïve metastatic castration-resistant prostate cancer. Abiraterone acetate plus prednisolone had an acceptable safety profile.Clinical trial registration noNCT01756638.