Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial

Ishibashi, Shun; Arai, Hidenori; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Yamashita, Shizuya

doi:10.1016/j.jacl.2017.10.006

Cited by 156 publications

(167 citation statements)

References 46 publications

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“…The FIRST study showed that, in the fenofibric acid group during the 104‐week treatment period, 2.7% of participants had a serum creatinine level >2.0 mg/dL and 20.7% and 2.1% of participants had a 1.5‐fold and 2‐fold increase from baseline, respectively, with these percentages being higher than those in the placebo group. Previous studies comparing the effects of pemafibrate with those of fenofibrate showed that pemafibrate had a smaller effect than fenofibrate on serum creatinine levels, which was also confirmed during our long‐term treatment of 52 weeks in people with type 2 diabetes (Table ).…”

Section: Discussionsupporting

confidence: 86%

“…Although further investigation is needed to justify the difference in the clinical profile of pemafibrate from that of other fibrates, pemafibrate is reported to have a good benefit–risk balance. Pemafibrate had a TG‐lowering effect equal to or greater than that of fenofibrate, but the rates of AEs in the pemafibrate group were lower than those in the fenofibrate group . Furthermore, pemafibrate, but not fenofibrate, decreased ALT and GGT levels.…”

Section: Discussionmentioning

confidence: 87%

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Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52‐week data from the PROVIDE study

Araki

Yamashita

Arai

et al. 2019

Diabetes Obesity Metabolism

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The aim of this study was to evaluate the efficacy and safety of pemafibrate in people with type 2 diabetes and hypertriglyceridaemia over a 52‐week period. Participants were randomly assigned to receive treatment with placebo or pemafibrate at a dose of 0.2 or 0.4 mg/d for 24 weeks (treatment period 1). The main results from treatment period 1 have been reported previously. The assigned treatment was continued up to week 52, except that the placebo was changed to pemafibrate 0.2 mg/d after week 24 (treatment period 2). The percentage changes in fasting serum triglyceride (TG) levels at week 52 (last observation carried forward) were −48.2%, −42.3%, and −46.4% in the placebo/pemafibrate 0.2 mg/d (n = 57), pemafibrate 0.2 mg/d (n = 54), and pemafibrate 0.4 mg/d (n = 55) groups, respectively. Levels of TG, non‐HDL cholesterol and total cholesterol stably decreased, whereas levels of HDL cholesterol increased with pemafibrate treatments over 52 weeks. Pemafibrate was well tolerated throughout the study period. The present study is the first to show that pemafibrate treatment substantially ameliorated lipid abnormalities and was well tolerated for 52 weeks in people with type 2 diabetes and hypertriglyceridaemia.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 87%

Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52‐week data from the PROVIDE study

Araki

Yamashita

Arai

et al. 2019

Diabetes Obesity Metabolism

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“…In the current investigation, no severe ADRs were recorded for pemafibrate. The drug has also been reported to have a lower incidence of adverse effects than fenofibrate in patients with dyslipidemia . Additional longer studies are needed to clarify the clinical advantage of pemafibrate with UDCA, especially with regard to effect and safety.…”

Section: Discussionmentioning

confidence: 99%

“…The new selective peroxisome proliferator‐activated receptor α modulator (SPPARM‐α), pemafibrate, was very recently approved for the treatment of dyslipidemia . Dyslipidemia is a common feature in PBC.…”

Section: Introductionmentioning

confidence: 99%

Biochemical and plasma lipid responses to pemafibrate in patients with primary biliary cholangitis

Joshita

Umemura

Yamashita

et al. 2019

Hepatology Research

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Aim Fibrate addition to ursodeoxycholic acid (UDCA) therapy has been shown to improve both liver biochemistry and long‐term prognosis in primary biliary cholangitis (PBC) patients showing an incomplete biochemical response to UDCA alone. We herein describe the clinical outcome of seven cases of PBC that received the new selective peroxisome proliferator‐activated receptor α modulator, pemafibrate, in combination with UDCA therapy to investigate the biochemical and plasma lipid responses to the drug. Methods Of 124 initially enrolled PBC patients, 12 treated with UDCA alone and seven receiving UDCA plus bezafibrate showed alkaline phosphatase (ALP) levels above the upper limit of normal (330 U/L). Ultimately, seven patients with PBC and dyslipidemia who had agreed to biweekly visits at our hospital for UDCA plus pemafibrate combination therapy were retrospectively analyzed. Results In the four cases that switched from bezafibrate to pemafibrate, ALP became significantly decreased (0.031) and γ‐glutamyltransferase tended to decrease (0.063) over the 3 months following pemafibrate addition. Two patients showed a greater than 50% reduction in ALP. No remarkable differences were observed for plasma lipid levels, alanine aminotransferase, aspartate aminotransferase, or the liver fibrosis marker Mac‐2 binding protein glycosylation isomer between these time points. No adverse drug reactions were recorded. Conclusions Pemafibrate might be another option for PBC patients with an incomplete response to UDCA therapy.

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“…The clinical study demonstrated minor fluctuations in both serum creatinine and cystatin C over 24 weeks with pemafibrate compared with the significant increase in these values with fenofibrate treatment. Because patients with CKD typically present with confounding diseases such as dyslipidemia, once approved, pemafibrate may be a suitable alternative agent for this population . In another case report, dosing of an aminoglycoside antibiotic cleared by the kidney corrected for eGFR‐creatinine resulted in overestimation of GFR, accumulation of the drug, and, ultimately, AKI in an elderly man.…”

Section: Recommendations For Renal Impairment Studies In Drug Developmentioning

confidence: 99%

Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies

Kar

Paglialunga

Islam

2018

The Journal of Clinical Pharma

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Glomerular filtration rate (GFR) is routinely used as a surrogate endpoint for the development of investigational drugs in clinical trials. GFR and staging of chronic kidney disease are typically assessed by measuring the concentration of endogenous serum biomarkers such as albumin and creatinine. However, creatinine is subject to high biological variability, and levels of creatinine do not rise until nearly 50% of kidney function is damaged, leading to inaccurate chronic kidney disease staging and false negatives. A newer biomarker for GFR, cystatin C, has been shown to be subject to less biological interference and more sensitive to early declines in kidney function. Cystatin C has also been shown to outperform creatinine as an indicator of true GFR and to add information about the occurrence of acute kidney injury. Comparison studies of cystatin C and creatinine continue to demonstrate its increased accuracy and sensitivity for changes in true GFR. While challenges remain for use of cystatin C, international agencies and working groups continue to validate cystatin C as a biomarker and accompanying GFR estimating equations for diagnostic and drug development use. In this review, we summarize these comparison studies, regulatory and industry guidelines, and clinical trial case studies for use of cystatin C in drug development.

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Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial

Abstract: Pemafibrate was superior to fenofibrate in terms of serum TG-lowering effect and hepatic and renal safety.

Cited by 156 publications

References 46 publications

Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52‐week data from the PROVIDE study

Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52‐week data from the PROVIDE study

Biochemical and plasma lipid responses to pemafibrate in patients with primary biliary cholangitis

Cystatin C Is a More Reliable Biomarker for Determining eGFR to Support Drug Development Studies

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