Efficacy and Safety of Pemafibrate Extended-Release Tablet: a Phase 3, Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group Comparison Trial
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AIMS: Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator that lowers serum triglyceride levels and increases high-density lipoprotein cholesterol levels, is approved for treating dyslipidemia as twice-daily immediate-release (IR) tablets. A once-daily extended-release (XR) tablet has also been developed. We aimed to confirm the non-inferiority of XR (0.2 or 0.4 mg/day; once daily) to IR (0.2 mg/day; twice daily) in lowering triglyceride levels in patients with hypertriglyceridemia. METHODS: This phase 3, multicenter, randomized, double-blind study included patients with fasting triglycerides ≥ 200 mg/dL who received IR (0.2 mg/day) or XR (0.2 or 0.4 mg/day). The primary efficacy endpoint was the percentage change in fasting triglyceride levels from baseline to 4, 8, and 12 weeks. Common treatment effects at weeks 4 through 12 were compared between groups using repeated analysis of covariance. RESULTS: In 356 randomized patients, fasting triglyceride levels decreased by 48.0%, 43.8%, and 48.0% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively, confirming the non-inferiority of both XR regimens to IR. The proportion of patients who achieved fasting triglycerides ＜150 mg/dL was 45.7%, 37.4%, and 51.7%, while the percentage change of triglycerides in the subgroup with baseline triglycerides ≥ 500 mg/dL was -59.3%, -52.2%, and -66.3% with IR 0.2, XR 0.2, and XR 0.4 mg/day, respectively. CONCLUSIONS: XR (0.2 and 0.4 mg/day) was non-inferior to IR (0.2 mg/day). XR 0.4 mg/day demonstrated a more potent triglyceride-lowering effect than XR 0.2 mg/day and should be considered for patients with high triglyceride levels.
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Data from Arai 2024 and Yamashita 2025 comparing different doses of pemafibrate showed no statistically significant difference in adverse events between doses, with a risk ratio of 0.67 (95% CI: 0.43, 1.05, p = 0.08) and I2 = 0%.
“Data from Arai 2024 and Yamashita 2025 comparing different doses of pemafibrate showed an RR of 0.67 (95% CI: 0.43, 1.05, p = 0.08), indicating no statistically significant difference in adverse events between doses (I2 = 0%) (Moderate certainty).”
From Pemafibrate for hypertriglyceridemia: a meta-analysis of randomized controlled trials evaluating efficacy and safety outcomes (2026) · cites this paper as Arai 2024
The Safety Endpoints results report no significant difference in total adverse-event incidence among the treatment groups, and Table 3 gives adverse-event counts for the different doses. The cited paper does not report the pooled risk ratio, 95% confidence interval, p-value, I², or certainty rating attributed to data from both studies. (LLM, conf=0.87)
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References 20 · Cited by 8
Research works printed but not linked: 13
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- Authors
- Arai, H., Yamashita, S., Araki, E., Yokote, K., Tanigawa, R., Saito, A., Yamasaki, S., Suganami, H., & Ishibashi, S.
- Affiliations
- National Center for Geriatrics and Gerontology (JP)
- Rinku General Medical Center (JP)
- Kumamoto Health Science University (JP)
- Chiba University (JP)
- Kowa (Japan) (JP)
- Jichi Medical University (JP)
- ORCID
- Venue
- Journal of Atherosclerosis and Thrombosis
- Publisher
- Japan Atherosclerosis Society
- Published
- 2024-11-01
- Volume
- 31
- Issue
- 11
- Pages
- 1517-1538
- ISSN
- 1340-3478 (ISSN-L)
- 1880-3873
- PMC
- PMC11537784
- OpenAlex
- W4394773819
- Cited by
- 8
- References
- 20
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- Journal of Atherosclerosis and Thrombosis (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- Abbott Japan
- Kowa Company
- Boehringer Ingelheim Japan
- Daiichi-Sankyo
- Novo Nordisk
- Astellas Pharma
- Shionogi
- Mitsubishi Tanabe Pharma Corporation
- Ono Pharmaceutical
- Novartis Pharma
- Pfizer Japan
- MSD K.K.
- Eli Lilly Japan
- Bayer Yakuhin
- Novo Nordisk Pharma
- Daiichi Sankyo Company
- Daiichi Sankyo Europe
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- pemafibrate, sustained-release formulation, immediate-release formulation, hypertriglyceridemia, triglyceride lowering, PPARα agonist, non-inferiority, once-daily dosing, dyslipidemia management, dose comparison
- MeSH terms
- Adult, Aged, Hypolipidemic Agents, Benzoxazoles, Butyrates, Delayed-Action Preparations, Double-Blind Method, Female, Humans, Male, Middle Aged, Phenylalanine, Tablets, Triglycerides, Hypertriglyceridemia, Treatment Outcome
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