A Qualitative Research Study of Experiences and Perceptions of People Living with Insulin Resistance Syndrome or Lipoatrophic Diabetes in Japan.

INTRODUCTION: There are few reports on the experiences and perceptions of people living with the rare diseases of insulin resistance syndrome or lipodystrophy. This study was designed to identify treatment experiences and perceptions of disease-related burdens among affected people, as well as their needs and priorities. We discussed how to meet identified needs and expectations, in addition to the types of therapeutic drugs and support required. METHODS: Qualitative data regarding participants' experiences and perceptions of the diseases were collected through individual interviews, advisory board meetings, and individual follow-up activities. Verbatim transcripts from recorded participants' statements were qualitatively analysed. RESULTS: Four women aged 30-41 years participated in the study, two with insulin resistance syndrome and two with lipoatrophic diabetes. The diseases not only took a heavy physical toll on these women, but they and their families were also affected psychologically, with some experiencing stigmatisation. There was a lack of information for participants about their disease and little public awareness of the disease. The needs identified include initiatives to promote an accurate understanding of these diseases, information booklets, consultation service for those affected by the diseases, less burdensome treatment options, and opportunities for peer communication. CONCLUSION: People living with insulin resistance syndrome or lipoatrophic diabetes have significant physical/psychological burdens and unmet needs. The following are highly desirable to alleviate the burdens: promoting proper understanding of the diseases; establishing a framework for dissemination of disease and treatment information to those living with the diseases; development of therapeutic drugs for these diseases; educational materials that raise public awareness; and opportunities for peer communication. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN000043693). A Japanese translation is available for this article.

Understanding potential participation barriers to improve trial design and outcomes: clinical trial simulation in palmoplantar pustulosis as a case study.

OBJECTIVES: Evaluate the experiences and perceptions of patients participating in a simulated clinical trial and identify ways to enhance future patient-centric trial designs. DESIGN: International, multicentre, non-interventional, virtual clinical trial visits with patient debriefs and advisory boards. SETTING: Virtual clinic visits and accompanying advisory boards. PARTICIPANTS: Nine patients with palmoplantar pustulosis for simulated trial visits; 14 patients and patient representatives for advisory boards. MAIN OUTCOME MEASURES: Qualitative responses to trial documentation, visit schedule and logistics, and trial design were collected during patient debriefs. Results were discussed at two virtual advisory board meetings. RESULTS: Patients identified key barriers to participation and potential difficulties encountered when attending trial visits and completing assessments. They also proposed recommendations to overcome these challenges. Patients recognised the need for comprehensive informed consent forms, but recommended use of non-technical language, brevity and additional support to aid understanding. Other trial documentations should be relevant to the disease and include known efficacy and safety of the study drug. Patients were concerned about receiving placebo, stopping existing medications and being unable to receive the study drug after trial completion; therefore, patients and physicians recommended an open-label extension following trial completion. Trial visits were too numerous (n=20) and too long (3-4 hours each); patients recommended improvements to the design to make best use of their time and reduce unnecessary waiting. They also requested financial and logistical support. Patients expressed a desire for study outcomes that matter to them, related to their ability to undertake normal daily activities and not be a burden to others. CONCLUSIONS: Simulated trials are an innovative method for assessing trial design and acceptance from a patient-centric perspective, enabling specific improvements to be made prior to trial initiation. Incorporation of recommendations from simulated trials could enhance trial recruitment and retention, and optimise trial outcomes and data quality.

Experience and Daily Burden of Patients with Chronic Kidney Disease Not Receiving Maintenance Dialysis or Renal Transplantation.

INTRODUCTION: Daily burden of patients with chronic kidney disease (CKD) who have not received maintenance dialysis or renal transplantation has not been well reported compared with patients receiving dialysis. We conducted a patient survey and an advisory board in Japan to investigate the experience and perception of CKD and its treatments from the patient's perspective. METHODS: An anonymous web survey (n = 342) was conducted in October and November 2020. Participants, who were recruited through multiple panels, aged 20 years or older, diagnosed with any stage of CKD, and who had neither received nor planned maintenance dialysis or renal transplantation were included. A questionnaire prepared under the medical advisor's guidance was used to collect the background information, burden of disease and treatments, and needs and expectations for future treatments. An advisory board with five patients nominated from a patient group was conducted in December 2020. Additional insights to interpret the results of the preceding survey were collected using pre-identified discussion topics. RESULTS: Establishing a diagnosis of CKD generally took a long time; approximately 20% of the patients waited more than 5 years before diagnosis. In daily life, patients were burdened with CKD-related symptoms (e.g., tinnitus, leg cramps) and behavioral restrictions, including diet. They also felt psychological burdens, such as concerns about possible future dialysis and/or renal transplantation, lack of awareness and understanding of disease among the other people in their lives, and financial burdens related to medical expenses. Furthermore, they felt a lack of communication in daily interactions with health care professionals and others around them, and they desired interaction with patients with CKD. CONCLUSION: Understanding the burdens and the thoughts of patients with CKD could inform discussions about the ways to improve communication with patients in daily practice, the role of the patient community, and new therapeutic options to address patients' expectations. TRIAL REGISTRATION: UMIN000042300.

Safety, pharmacokinetics and pharmacodynamics of BI 655064 in phase 1 clinical trials in healthy Chinese and Japanese subjects.

AIMS: To evaluate the safety, pharmacokinetics and pharmacodynamics of BI 655064 in healthy Chinese and Japanese subjects after administration of single doses of 80-240 mg and multiple dosing of 240 mg once weekly over 4 weeks. METHODS: Two phase 1, double-blind, placebo-controlled studies were conducted (single-rising doses of BI 655064 in Chinese/Japanese male subjects [n = 12 per BI 655064 dose group] or repeated 240 mg BI 655064 in Chinese male subjects [n = 9]). Plasma samples were collected to investigate BI 655064 pharmacokinetics, pharmacodynamics (CD40 receptor occupancy [RO]) and immunogenicity, along with the safety and tolerability of BI 655064. RESULTS: BI 655064 showed good overall tolerability following single-dose administration of 80-240 mg and repeated administration of 240 mg BI 655064 over 4 weeks. More Chinese subjects reported adverse events compared with Japanese subjects following single-dose administration (59.4% vs 3.1%). BI 655064 exhibited nonlinear, saturable kinetics, with higher doses resulting in slower apparent clearance (0.514-0.713 mL min-1 ), and disproportionately higher total exposure (AUC0-inf ; 5610-7780 µg·h mL-1 ) and maximum plasma concentration (15 700-21 300 ng mL-1 ) with 240 mg BI 655064. Ninety percent inhibition of CD40 RO was achieved with doses ≥120 mg, and a direct relationship between BI 655064 plasma concentration and inhibition of CD40 RO was observed. Most subjects had a positive treatment-emergent antidrug antibody response. CONCLUSIONS: BI 655064 pharmacokinetic and safety profiles in East Asian male subjects were consistent with those observed in a Western population. No adjustments in the BI 655064 dosing recommendations are warranted for future clinical trials.

Post-marketing surveillance on the long-term use of dabigatran in Japanese patients with nonvalvular atrial fibrillation: Preliminary report of the J-dabigatran surveillance.

BACKGROUND/AIM: A post-marketing surveillance (PMS) study is being conducted to investigate the safety and effectiveness of the long-term use of dabigatran etexilate (dabigatran) in Japanese patients with nonvalvular atrial fibrillation (NVAF). Results of an interim analysis of this prospective cohort study including patient characteristics and adverse drug reactions (ADRs) collected up to September 17, 2014 are reported here. METHODS: Patients with NVAF who began to receive dabigatran for the first time from December 2011 to November 2013 were enrolled at 1042 study sites in Japan. Clinical parameters included patient characteristics, dabigatran dose strength, concomitant medications and outcome events. All outcome events were collected as serious and non-serious adverse events (AEs). ADRs were evaluated in this report. Pre-defined safety events of special interest for intensive survey were serious and non-serious outcome events such as myocardial infarction, as well as the total number of hemorrhage and gastrointestinal disorders. RESULTS: A total of 6772 patients were registered. The safety analysis set included 6148 patients; mean age was 70.8±9.9 (SD) years: 2323 patients (37.8%) were aged 75 years or older. Males accounted for 66.8% of the patients. Mean CHADS2 score was 1.8±1.3; the CHADS2 score was 0 in 13.6%, 1 in 31.3%, 2 in 25.9%, 3 in 14.9%, and 4 to 6 in 11.1% of the patients. Of the 6148 patients, 1701 patients (27.7%) were switchers from warfarin and 4407 patients (71.7%) were non-switchers (OAC naïve patients). Treatment adherence was assessed for the first 3 months from the start of treatment for this analysis. Total 5656 patients (92.0%) reported taking dabigatran twice daily (bid) every day according to the label recommendation. During the follow up period [mean duration of follow up: 498±259 days (corresponding to 8386 patient-years)], pre-defined safety events of special interest for intensive survey (reported as serious ADRs) were: myocardial infarction, reported in 5 patients (0.06 per 100 patient-years); serious hemorrhage, reported in 46 patients (0.55 per 100 patient-years); and gastrointestinal disorders (non-hemorrhagic), reported in 11 patients (0.13 per 100 patient-years). Fifteen patients had ADRs with fatal outcome. CONCLUSIONS: The interim findings from this 6148 patient PMS study further corroborate the favorable safety profile of dabigatran as demonstrated previously in controlled clinical trials. (ClinicalTrials.gov number, NCT01491178.).

Tolerability of nintedanib (BIBF 1120) in combination with docetaxel: a phase 1 study in Japanese patients with previously treated non-small-cell lung cancer.

BACKGROUND: This phase I, open-label study evaluated the safety/tolerability and maximum tolerated dose of second-line nintedanib combined with docetaxel in Japanese patients with advanced non-small-cell lung cancer. METHODS: Eligible patients received docetaxel 60 or 75 mg/m(2) (day 1) plus nintedanib 100, 150, or 200 mg twice daily (bid; days 2-21) in 21-day cycles. Standard 3 + 3 dose escalations were performed separately in patient cohorts with a body surface area (BSA) of less than 1.5 m(2) (BSA <1.5) and BSA greater than or equal to 1.5, respectively. RESULTS: Forty-two patients (17 BSA <1.5, 25 BSA ≥ 1.5) were treated. The maximum tolerated dose of nintedanib was 150 and 200 mg bid in patients with BSA less than 1.5 and BSA greater than or equal to 1.5 (BSA ≥ 1.5), respectively, in combination with 75 mg/m(2) of docetaxel. Dose-limiting toxicities (all grade 3 hepatic enzyme elevations) occurred in 12 patients (six per cohort). Drug-related adverse events included neutropenia (95%), leukopenia (83%), fatigue (76%), alopecia (71%), decreased appetite (67%), and elevations in alanine aminotransferase (64%) and aspartate aminotransferase (64%). All hepatic enzyme elevations were reversible and manageable with dose reduction or discontinuation. Among 38 evaluable patients, 10 (26%) had a partial response and 18 (47%) had stable disease. CONCLUSION: Continuous treatment with second-line nintedanib combined with docetaxel was manageable and showed promising signs of efficacy in Japanese patients with advanced non-small-cell lung cancer.

Efficacy and tolerability of telmisartan plus amlodipine in asian patients not adequately controlled on either monotherapy or on low-dose combination therapy.

Objective. To evaluate the efficacy and safety of the telmisartan plus amlodipine (T/A) single-pill combination (SPC) in Asian patients with hypertension whose blood pressure (BP) was not adequately controlled on either monotherapy or on low-dose combination therapy. Patients and Methods. Data are presented from five Boehringer Ingelheim-sponsored phase 3, double-blind, 8-week, studies: two studies in nonresponders to amlodipine (data pooled for amlodipine), two studies on nonresponders to telmisartan (pooled data), and one on nonresponders to low-dose T/A SPC. Results. After 8 weeks' treatment, mean reductions from the reference baseline in diastolic BP (DBP; primary endpoint), systolic BP (SBP), and SBP, DBP goal, and response rates were higher with the T/A SPC than respective monotherapies. The T80/A5 SPC resulted in greater reductions in DBP and SBP, and higher DBP goal and response rate than the low-dose T40/A5 SPC. Peripheral edema incidence was low (amlodipine 0.5%, telmisartan 0.0%, and T/A SPC 0.7%). Discussion and Conclusion. In Asian patients whose BP is not adequately controlled with telmisartan or amlodipine monotherapy, T/A SPC treatment results in greater BP reduction, and higher DBP and SBP goal and response rates. The safety and tolerability of the T/A SPC are comparable to those of the respective monotherapies and consistent with those reported in previous studies.