Effects of Yogurt Intake on Cardiovascular Strain during Outdoor Interval Walking Training by Older People in Midsummer: A Randomized Controlled Study.

We examined whether post-exercise yogurt intake reduced cardiovascular strain during outdoor interval walking training (IWT) in older people during midsummer. The IWT is a training regimen repeating slow and fast walking at ~40% and ≥70% peak aerobic capacity, respectively, for 3 min each per set, ≥5 sets per day, and ≥4 days/wk. We randomly divided 28 male and 75 female older people (~73 yr), who had performed IWT ≥12 months, into a carbohydrate group (CHO-G) consuming jelly (45 g CHO, 180 kcal) and a yogurt group (YGT-G) consuming a yogurt drink (9.3 g protein, 39 g CHO, 192 kcal) immediately after daily IWT for 56 days while monitoring exercise intensity and heart rate (HR) with portable devices. We analyzed the results in 39 subjects for the CHO-G and 37 subjects for the YGT-G who performed IWT ≥ 4 days/wk, ≥60 min total fast walking/wk, and ≥4 sets of each walk/day. We found that the mean HR for fast walking decreased significantly from the baseline after the 30th day in the YGT-G (p < 0.03), but not in the CHO-G (p = 1.00). There were no significant differences in training achievements between the groups. Thus, post-exercise yogurt intake might reduce cardiovascular strain during outdoor walking training in older people.

Comparison of the Pharmacokinetics of RIPK1 Inhibitor GSK2982772 in Healthy Western and Japanese Subjects.

BACKGROUND AND OBJECTIVES: GSK2982772 is an oral small-molecule RIPK1 inhibitor with potential therapeutic efficacy in immune-mediated inflammatory diseases (IMIDs). An inter-ethnic comparison of GSK2982772 pharmacokinetics was conducted based on data from Western (Study 1) and Japanese subjects (Study 2). METHODS: Both studies were single-centre, randomised, double-blind, placebo-controlled studies with objectives to assess the safety and characterise the pharmacokinetics of GSK2982772. Western subjects in Study 1 (NCT03305419), Part A (N = 15), were randomly assigned to receive 120 mg three times daily (TID), 240 mg TID, or 360 mg twice daily (BID) doses of GSK2982772, or placebo (TID or BID) for 1 day. Part B subjects (N = 47) received GSK2982772 120 mg TID, 240 mg TID, or placebo TID for 14 days. Japanese subjects in Study 2 (N = 13) (NCT03590613) were randomly assigned to receive TID doses of GSK2982772 60, 120, 240 mg TID or placebo TID for 1 day. RESULTS: GSK2982772 was well tolerated and adverse events were generally mild. Maximum observed plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma drug concentration versus time curve after the first GSK2982772 dose (AUC(0-7)) of 120 and 240 mg, and (AUC(0-24)) values for the 120 and 240 mg TID doses over a single day were similar in Japanese and Western subjects. CONCLUSIONS: The pharmacokinetics and tolerability of GSK2982772 were similar between Western and Japanese subjects, justifying inclusion of Japanese subjects in future global clinical studies to assess the therapeutic potential of RIPK1 inhibition for the treatment of IMIDs. Clinical Trials: NCT03305419 and NCT03590613 available from http://www.clinicaltrials.gov .

Long-term safety and efficacy of ambrisentan in Japanese adults with pulmonary arterial hypertension.

OBJECTIVE: To investigate the safety and efficacy of long-term administration of ambrisentan in Japanese adults with pulmonary arterial hypertension (PAH). RESEARCH DESIGN AND METHODS: In this open-label extension of a preceding multicenter dose-escalation study, 21 Japanese patients with PAH received treatment with 5 or 10 mg of ambrisentan once daily and were comprehensively evaluated every 12 weeks. The primary endpoint was the safety of long-term ambrisentan administration, as defined by the incidence and severity of adverse events. The secondary (efficacy) endpoints were change in exercise capacity (as indicated by 6-minute walk distance), World Health Organization functional class, Borg dyspnea index, plasma brain natriuretic peptide level, cardiopulmonary hemodynamics, and time to clinical worsening of PAH. CLINICAL TRIAL REGISTRATION: NCT00554619. RESULTS: The mean total duration of treatment (i.e., including the preceding dose-escalation study) was approximately 139 weeks. There were fewer adverse events related to ambrisentan in this study than in the preceding study, and we identified no new safety signals that might preclude the long-term use of ambrisentan among Japanese adults with PAH. Improvements observed in efficacy endpoints in the preceding study were maintained in the present study. LIMITATIONS: This study did not include a control group and lacked the statistical power to reach definite conclusions regarding the efficacy of ambrisentan. CONCLUSION: Our results suggest that long-term administration of ambrisentan is well tolerated and efficacious for Japanese adults with PAH.

Efficacy, safety, and pharmacokinetics of ambrisentan in Japanese adults with pulmonary arterial hypertension.

OBJECTIVE: To investigate the efficacy, safety, and pharmacokinetics of ambrisentan in Japanese adults with pulmonary arterial hypertension (PAH). RESEARCH DESIGN AND METHODS: In this open-label, uncontrolled, dose-escalation study, 25 Japanese patients with PAH were scheduled to receive 5 mg of ambrisentan once daily for the first 12 weeks, and 10 mg once daily for an additional 12 weeks. The primary endpoint was improvement in exercise capacity from baseline which was indicated by 6-minute walk distance; the secondary endpoints included World Health Organization functional class, Borg dyspnea index, plasma brain natriuretic peptide level, and cardiopulmonary hemodynamics. CLINICAL TRIAL REGISTRATION: NCT00540436. RESULTS: At week 24, improvements were noted in all endpoints, with no clinically significant elevation of serum aminotransferase level. Pharmacokinetics in these Japanese patients was similar to that of non-Japanese populations, suggesting that once-daily dosing is appropriate in Japanese patients. Ambrisentan was generally well tolerated. No new safety signals were identified. LIMITATION: This study lacked a control group and was insufficiently powered to reach definitive conclusions on the efficacy of ambrisentan. CONCLUSION: Ambrisentan is considered as safe and effective for Japanese adults with PAH.