fenofibrate and Fatty Liver, Nonalcoholic studies

Pharmavit: a polyvitamin product, comprising vitamins A, D2, B1, B2, B6, C, E, nicotinamide, & calcium pantothene; may be a promising agent for application to human populations exposed to carcinogenic and genetic hazards of ionizing radiation; RN from CHEMLINE

Research Excerpts

Excerpt	Relevance	Reference
"In patients with NASH with hypertriglyceridemia treated with CILO and FIR, fenofibrate was safe and effectively mitigated increases in triglycerides associated with acetyl-CoA carboxylase inhibition."	9.69	Fenofibrate Mitigates Hypertriglyceridemia in Nonalcoholic Steatohepatitis Patients Treated With Cilofexor/Firsocostat. ( Bhandari, BR; Chuang, JC; Chung, C; Ding, D; Harting, E; Huss, RS; Kohli, A; Lawitz, EJ; Loomba, R; Myers, RP; Ruane, PJ, 2023)
" Plasma from overweight patients with non-alcoholic fatty liver disease (NAFLD) and hypertriglyceridemia, participating in a randomized placebo-controlled study investigating the effects of 12 weeks treatment with fenofibrate or omega-3 free carboxylic acids (OM-3CA) (200 mg or 4 g per day, respectively), were analyzed for eicosanoids and related PUFA species, N-acylethanolamines (NAE) and ceramides."	9.41	Omega-3 carboxylic acids and fenofibrate differentially alter plasma lipid mediators in patients with non-alcoholic fatty liver disease. ( Camacho-Muñoz, D; Kiezel-Tsugunova, M; Kiss, O; Lind, L; Nicolaou, A; Oscarsson, J; Ryaboshapkina, M; Sundén, M; Uddin, M, 2021)
"The purpose of this study was to assess and compare the effect of fenofibrate alone or in combination with pentoxifylline on the measured biochemical parameters, inflammatory pathway and liver stiffness in patients with non-alcoholic fatty liver disease."	9.20	Comparative clinical study between the effect of fenofibrate alone and its combination with pentoxifylline on biochemical parameters and liver stiffness in patients with non-alcoholic fatty liver disease. ( El-Haggar, SM; Mostafa, TM, 2015)
"Nonalcoholic fatty liver disease (NAFLD) is known to be a health-related problem; there is no proven treatment for NAFLD."	6.84	Comparison of fenofibrate and pioglitazone effects on patients with nonalcoholic fatty liver disease. ( Akbarieh, S; Gohari, S; Heydari, AH; Jafari, S; Jameshoorani, M; Sajedi, B; Yaghoubi, M, 2017)
"Fenofibrate (FNB) can activate peroxisome proliferator-activated receptor α (PPARα) to increase fatty acid oxidation and ameliorate NAFLD."	5.91	Engineered Fenofibrate as Oxidation-Sensitive Nanoparticles with ROS Scavenging and PPARα-Activating Bioactivity to Ameliorate Nonalcoholic Fatty Liver Disease. ( Chen, D; Du, K; Huang, X; Peng, A; Qi, R; Yang, Q; Zhang, J, 2023)
"Fenofibrate is a peroxisome proliferator-activated receptor α agonist widely used in clinical therapy to effectively ameliorate the development of NAFLD, but its mechanism of action is incompletely understood."	5.91	Fenofibrate improves hepatic steatosis, insulin resistance, and shapes the gut microbiome via TFEB-autophagy in NAFLD mice. ( Chen, H; Chen, Y; Geng, Z; Huang, M; Li, L; Liu, J; Ma, L; Ma, Y; Wang, D; Wang, H; Wang, X; Wen, D; Zhang, D; Zhu, X; Zou, C, 2023)
"Non-alcoholic fatty liver disease (NAFLD) has been increasing in association with the epidemic of obesity and diabetes."	5.72	Peroxisomal Fitness: A Potential Protective Mechanism of Fenofibrate against High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice. ( Dorotea, D; Ha, H; Jiang, S; Oh, GT; Piao, L; Uddin, MJ; Yu, X, 2022)
"In patients with NASH with hypertriglyceridemia treated with CILO and FIR, fenofibrate was safe and effectively mitigated increases in triglycerides associated with acetyl-CoA carboxylase inhibition."	5.69	Fenofibrate Mitigates Hypertriglyceridemia in Nonalcoholic Steatohepatitis Patients Treated With Cilofexor/Firsocostat. ( Bhandari, BR; Chuang, JC; Chung, C; Ding, D; Harting, E; Huss, RS; Kohli, A; Lawitz, EJ; Loomba, R; Myers, RP; Ruane, PJ, 2023)
"We have developed a co-assembled nanosystem based on fenofibrate and ketoprofen by tactfully utilizing their simultaneous benzophenone interaction, which greatly enhances the bioavailability of fenofibrate and plays a role in the dual-targeted treatment of NAFLD by reducing hepatic lipid accumulation and inflammatory responses."	5.56	Simultaneous co-assembly of fenofibrate and ketoprofen peptide for the dual-targeted treatment of nonalcoholic fatty liver disease (NAFLD). ( Fan, G; Liu, J; Ma, C; Ren, C; Shang, Y; Wang, Z; Yang, C; Yang, L; Zhang, J, 2020)
" Plasma from overweight patients with non-alcoholic fatty liver disease (NAFLD) and hypertriglyceridemia, participating in a randomized placebo-controlled study investigating the effects of 12 weeks treatment with fenofibrate or omega-3 free carboxylic acids (OM-3CA) (200 mg or 4 g per day, respectively), were analyzed for eicosanoids and related PUFA species, N-acylethanolamines (NAE) and ceramides."	5.41	Omega-3 carboxylic acids and fenofibrate differentially alter plasma lipid mediators in patients with non-alcoholic fatty liver disease. ( Camacho-Muñoz, D; Kiezel-Tsugunova, M; Kiss, O; Lind, L; Nicolaou, A; Oscarsson, J; Ryaboshapkina, M; Sundén, M; Uddin, M, 2021)
"The purpose of this study was to assess and compare the effect of fenofibrate alone or in combination with pentoxifylline on the measured biochemical parameters, inflammatory pathway and liver stiffness in patients with non-alcoholic fatty liver disease."	5.20	Comparative clinical study between the effect of fenofibrate alone and its combination with pentoxifylline on biochemical parameters and liver stiffness in patients with non-alcoholic fatty liver disease. ( El-Haggar, SM; Mostafa, TM, 2015)
" To assess whether OEA can also regulate non-alcoholic fatty liver disease (NAFLD) caused by fat accumulation, we administrated OEA or fenofibrate in Sprague Dawley (SD) rats fed with a high fat diet (HFD)."	3.81	Effect of oleoylethanolamide on diet-induced nonalcoholic fatty liver in rats. ( Chen, L; Fu, J; Li, L; Lin, X; Qiu, Y; Ren, J; Xu, Y, 2015)
"Nonalcoholic fatty liver disease (NAFLD) is known to be a health-related problem; there is no proven treatment for NAFLD."	2.84	Comparison of fenofibrate and pioglitazone effects on patients with nonalcoholic fatty liver disease. ( Akbarieh, S; Gohari, S; Heydari, AH; Jafari, S; Jameshoorani, M; Sajedi, B; Yaghoubi, M, 2017)
"Nonalcoholic fatty liver disease (NAFLD), caused by an accumulation of fat deposits in hepatocytes, prevalently affects at least one-third of the world's population."	2.82	Impact of fenofibrate on NAFLD/NASH: A genetic perspective. ( Jamialahmadi, T; Johnston, TP; Mahmoudi, A; Sahebkar, A, 2022)
"Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common causes of elevated liver enzymes in the general population."	2.49	Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. ( Aramin, H; Eslami, L; Malekzadeh, R; Merat, S; Nasseri-Moghaddam, S, 2013)
"Fenofibrate (FNB) can activate peroxisome proliferator-activated receptor α (PPARα) to increase fatty acid oxidation and ameliorate NAFLD."	1.91	Engineered Fenofibrate as Oxidation-Sensitive Nanoparticles with ROS Scavenging and PPARα-Activating Bioactivity to Ameliorate Nonalcoholic Fatty Liver Disease. ( Chen, D; Du, K; Huang, X; Peng, A; Qi, R; Yang, Q; Zhang, J, 2023)
"Strongest NAFLD developed in mice fed 45%HFD, and it was inhibited in WT mice."	1.91	Down-regulation of hepatic CLOCK by PPARα is involved in inhibition of NAFLD. ( Dai, M; Liu, A; Luo, J; Xi, Y; Xu, L; Yan, Z; Yang, J; Zhang, H, 2023)
"Fenofibrate is a peroxisome proliferator-activated receptor α agonist widely used in clinical therapy to effectively ameliorate the development of NAFLD, but its mechanism of action is incompletely understood."	1.91	Fenofibrate improves hepatic steatosis, insulin resistance, and shapes the gut microbiome via TFEB-autophagy in NAFLD mice. ( Chen, H; Chen, Y; Geng, Z; Huang, M; Li, L; Liu, J; Ma, L; Ma, Y; Wang, D; Wang, H; Wang, X; Wen, D; Zhang, D; Zhu, X; Zou, C, 2023)
"Non-alcoholic fatty liver disease (NAFLD) has been increasing in association with the epidemic of obesity and diabetes."	1.72	Peroxisomal Fitness: A Potential Protective Mechanism of Fenofibrate against High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice. ( Dorotea, D; Ha, H; Jiang, S; Oh, GT; Piao, L; Uddin, MJ; Yu, X, 2022)
"When fenofibrate was administered to the fatty liver model created via GAN administration and liver steatosis was assessed, a reduction in liver fat deposition was observed, and this model was shown to be useful in drug evaluations involving fatty liver."	1.62	Establishment of an Adult Medaka Fatty Liver Model by Administration of a Gubra-Amylin-Nonalcoholic Steatohepatitis Diet Containing High Levels of Palmitic Acid and Fructose. ( Fujisawa, K; Kondo, K; Matsumoto, T; Nishimura, Y; Okubo, S; Sakaida, I; Takami, T; Yamada, Y; Yamamoto, N, 2021)
"Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation and imbalances in lipid metabolism in the liver."	1.62	Hepatic ( Chae, YC; Choi, JH; Choi, SS; Eom, HJ; Hong, CH; Hyun, J; Jang, HJ; Khim, KW; Kim, H; Kim, S; Koh, EH; Lee, YH; Nam, D; Park, J; Park, NH; Shin, KJ; Woo, CY, 2021)
"Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and important risk factor for cardiac diseases, diabetes and extrahepatic cancers."	1.56	Synthesis of natural 3'-Prenylchalconaringenin and biological evaluation of ameliorating non-alcoholic fatty liver disease and metabolic syndrome. ( Hao, L; Hao, S; Sun, H; Wang, Z; Yu, P; Zhang, M; Zhang, X, 2020)
"We have developed a co-assembled nanosystem based on fenofibrate and ketoprofen by tactfully utilizing their simultaneous benzophenone interaction, which greatly enhances the bioavailability of fenofibrate and plays a role in the dual-targeted treatment of NAFLD by reducing hepatic lipid accumulation and inflammatory responses."	1.56	Simultaneous co-assembly of fenofibrate and ketoprofen peptide for the dual-targeted treatment of nonalcoholic fatty liver disease (NAFLD). ( Fan, G; Liu, J; Ma, C; Ren, C; Shang, Y; Wang, Z; Yang, C; Yang, L; Zhang, J, 2020)
"Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common clinico-pathological conditions that affect millions of patients worldwide."	1.48	Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models. ( Bhoi, B; Das, N; Giri, SR; Jain, MR; Kadam, S; Karmakar, E; Patel, H; Patel, PR; Ranvir, R; Rath, A; Rathod, R; Roy, SS; Swain, P; Trivedi, C; Wahli, W, 2018)
"Moreover, this work implies the enhanced liver fibrosis (ELF) panel diagnostic performance in diagnosis of any and moderate degree of fibrosis in rats with NAFLD."	1.46	Potential involvement of PPAR α activation in diminishing the hepatoprotective effect of fenofibrate in NAFLD: Accuracy of non- invasive panel in determining the stage of liver fibrosis in rats. ( Abd-Elaziz, LF; Boctor, SS; El-Kharashi, OA; Hamed, AM, 2017)
"Hugan Qingzhi tablets alleviates hyperlipidemia and inflammation in rats fed with high-fat diet possibly by activating AMPK pathway and suppress NF-αB activity to arrest the progression of nonalcoholic fatty liver disease."	1.46	[Effect of Hugan Qingzhi tablets on AMPK pathway activation and NF-κB-p65 protein expression in the liver of rats with nonalcoholic fatty liver disease]. ( Tang, WJ; Xia, F; Yao, XR; Zhou, BJ, 2017)

Research

Studies (46)

Authors

Clinical Trials (2)

Trial Overview

Trial Outcomes

Percentage of Participants Who Experienced Grade 3 or Higher Laboratory Abnormalities

Timeframe	Studies, this research(%)	All Research%
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	0 (0.00)	29.6817
2010's	27 (58.70)	24.3611
2020's	19 (41.30)	2.80

Authors	Studies
Romero, FA	1
Jones, CT	1
Xu, Y	2
Fenaux, M	1
Halcomb, RL	1
Zhang, M	1
Wang, Z	2
Hao, S	1
Hao, L	1
Zhang, X	1
Yu, P	1
Sun, H	1
Fujisawa, K	1
Takami, T	1
Okubo, S	1
Nishimura, Y	1
Yamada, Y	1
Kondo, K	1
Matsumoto, T	1
Yamamoto, N	1
Sakaida, I	1
Camacho-Muñoz, D	1
Kiezel-Tsugunova, M	1
Kiss, O	1
Uddin, M	1
Sundén, M	1
Ryaboshapkina, M	1
Lind, L	1
Oscarsson, J	1
Nicolaou, A	1
Lee, YH	1
Jang, HJ	1
Kim, S	1
Choi, SS	1
Khim, KW	1
Eom, HJ	1
Hyun, J	1
Shin, KJ	1
Chae, YC	1
Kim, H	1
Park, J	1
Park, NH	1
Woo, CY	1
Hong, CH	1
Koh, EH	1
Nam, D	1
Choi, JH	1
Mahmoudi, A	2
Butler, AE	1
Jamialahmadi, T	2
Sahebkar, A	3
Lawitz, EJ	1
Bhandari, BR	1
Ruane, PJ	1
Kohli, A	1
Harting, E	1
Ding, D	1
Chuang, JC	2
Huss, RS	2
Chung, C	2
Myers, RP	2
Loomba, R	1
Honda, A	1
Kamata, S	1
Akahane, M	1
Machida, Y	1
Uchii, K	1
Shiiyama, Y	1
Habu, Y	1
Miyawaki, S	1
Kaneko, C	1
Oyama, T	1
Ishii, I	1
Johnston, TP	1
Vijayakumar, A	1
Okesli-Armlovich, A	1
Wang, T	1
Olson, I	1
Seung, M	1
Kusam, S	1
Hollenback, D	1
Mahadevan, S	1
Marchand, B	1
Toteva, M	1
Breckenridge, DG	1
Trevaskis, JL	1
Bates, J	1
Jiang, S	1
Uddin, MJ	1
Yu, X	1
Piao, L	1
Dorotea, D	1
Oh, GT	1
Ha, H	1
Alemán, MN	1
Sánchez, SS	1
Honoré, SM	1
Akbari, R	1
Yaghooti, H	1
Jalali, MT	1
Khorsandi, LS	1
Mohammadtaghvaei, N	1
Du, K	1
Huang, X	1
Peng, A	1
Yang, Q	1
Chen, D	1
Zhang, J	2
Qi, R	3
Luo, J	2
Yan, Z	2
Dai, M	2
Xu, L	3
Zhang, H	2
Xi, Y	2
Yang, J	2
Liu, A	2
Dandan, M	1
Han, J	1
Mann, S	1
Kim, R	1
Li, K	1
Mohammed, H	1
Zhu, K	1
Billin, AN	1
Hellerstein, M	1
Zhang, D	1
Ma, Y	1
Liu, J	3
Wang, D	1
Geng, Z	1
Wen, D	1
Chen, H	1
Wang, H	1
Li, L	3
Zhu, X	1
Wang, X	1
Huang, M	1
Zou, C	1
Chen, Y	1
Ma, L	1
Ma, C	1
Shang, Y	1
Yang, L	1
Yang, C	1
Ren, C	1
Fan, G	1
Abdelmoneim, D	1
El-Adl, M	1
El-Sayed, G	1
El-Sherbini, ES	1
Rajamoorthi, A	1
Arias, N	1
Basta, J	1
Lee, RG	1
Baldán, Á	1
Yaghoubi, M	1
Jafari, S	1
Sajedi, B	1
Gohari, S	1
Akbarieh, S	1
Heydari, AH	1
Jameshoorani, M	1
Jain, MR	1
Giri, SR	1
Bhoi, B	1
Trivedi, C	1
Rath, A	1
Rathod, R	1
Ranvir, R	1
Kadam, S	1
Patel, H	1
Swain, P	1
Roy, SS	1
Das, N	1
Karmakar, E	1
Wahli, W	2
Patel, PR	1
Cao, YN	1
Baiyisaiti, A	1
Wong, CW	1
Hsu, SH	1
Yang, M	1
Chen, Z	1
Xiao, C	1
Tang, W	1
Zhou, B	1
van den Hoek, AM	1
van der Hoorn, JW	1
Maas, AC	1
van den Hoogen, RM	1
van Nieuwkoop, A	1
Droog, S	1
Offerman, EH	1
Pieterman, EJ	1
Havekes, LM	1
Princen, HM	1
Eslami, L	1
Merat, S	1
Malekzadeh, R	1
Nasseri-Moghaddam, S	1
Aramin, H	1
Chew, GT	1
Watts, GF	1
Zhou, C	1
Zhou, J	1
Han, N	1
Liu, Z	1
Xiao, B	1
Yin, J	1
Chen, L	3
Lin, X	1
Ren, J	1
Fu, J	1
Qiu, Y	1
Zhang, N	1
Lu, Y	1
Shen, X	1
Bao, Y	1
Cheng, J	1
Li, B	1
Zhang, Q	2
El-Haggar, SM	1
Mostafa, TM	1
Zhang, Y	1
Cui, Y	1
Wang, XL	1
Shang, X	1
Qi, ZG	1
Xue, J	1
Zhao, X	1
Deng, M	1
Xie, ML	1
Zhu, Y	1
Wu, J	1
Zheng, Q	1
Dong, J	1
Jiang, J	1
Abd El-Haleim, EA	2
Bahgat, AK	2
Saleh, S	2
Montagner, A	1
Polizzi, A	1
Fouché, E	1
Ducheix, S	1
Lippi, Y	1
Lasserre, F	1
Barquissau, V	1
Régnier, M	1
Lukowicz, C	1
Benhamed, F	1
Iroz, A	1
Bertrand-Michel, J	1
Al Saati, T	1
Cano, P	1
Mselli-Lakhal, L	1
Mithieux, G	1
Rajas, F	1
Lagarrigue, S	1
Pineau, T	1
Loiseau, N	1
Postic, C	1
Langin, D	1
Guillou, H	1
Jiang, M	1
Xin, Y	1
Wang, J	1
Liu, Y	1
Jiang, X	1
Xuan, S	1
Williams, KH	1
Sullivan, DR	1
Nicholson, GC	1
George, J	1
Jenkins, AJ	1
Januszewski, AS	1
Gebski, VJ	1
Manning, P	1
Tan, YM	1
Donoghoe, MW	1
Ehnholm, C	1
Young, S	1
O'Brien, R	1
Buizen, L	1
Twigg, SM	1
Keech, AC	1
Cao, Y	1
Chen, C	1
Wang, Y	1
Yoon, S	1
Kim, J	1
Lee, H	2
Lim, J	1
Yang, H	1
Shin, SS	1
Yoon, M	1
Hamed, AM	1
El-Kharashi, OA	1
Boctor, SS	1
Abd-Elaziz, LF	1
Yao, XR	1
Xia, F	1
Tang, WJ	1
Zhou, BJ	1
van der Veen, JN	1
Lingrell, S	1
Gao, X	1
Takawale, A	1
Kassiri, Z	1
Vance, DE	1
Jacobs, RL	1
Lalloyer, F	2
Wouters, K	1
Baron, M	2
Caron, S	1
Vallez, E	2
Vanhoutte, J	1
Baugé, E	1
Shiri-Sverdlov, R	1
Hofker, M	1
Staels, B	2
Tailleux, A	2
Leroyer, AS	1
Majd, Z	1
Bantubungi, K	1
Chinetti-Gbaguidi, G	1
Delerive, P	1
Boulanger, CM	1
Walter, R	1
Wanninger, J	1
Bauer, S	1
Eisinger, K	1
Neumeier, M	1
Weiss, TS	1
Amann, T	1
Hellerbrand, C	1
Schäffler, A	1
Schölmerich, J	1
Buechler, C	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
A Proof of Concept, Open-Label Study Evaluating the Safety, Tolerability, and Efficacy of Regimens in Subjects With Nonalcoholic Steatohepatitis (NASH)[NCT02781584]	Phase 2	220 participants (Actual)	Interventional	2016-06-13	Completed
Comparative Clinical Study to Evaluate the Possible Beneficial Effect of Empagliflozin Versus Pioglitazone on Non-diabetic Patients With Non-Alcoholic Steatohepatitis[NCT05605158]	Phase 3	56 participants (Anticipated)	Interventional	2022-11-30	Not yet recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline time point, up to and including the date of last dose of study drug plus 30 days for subjects who permanently discontinued study drug. If baseline laboratory data were missing, then any abnormality of at least Grade 1 was considered treatment emergent. Graded laboratory abnormalities were defined using the grading scheme in the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 for Cohorts 1-9 and CTCAE Version 5.0 for Cohorts 10-13. (NCT02781584)
Timeframe: Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.

Percentage of Participants Who Experienced Treatment Emergent Serious Adverse Events

Intervention	percentage of participants (Number)
Cohort 1: SEL 18 mg (Non-cirrhotic)	20
Cohort 2: FIR 20 mg (Non-cirrhotic)	20
Cohort 3: CILO 30 mg (Non-cirrhotic)	40
Cohort 4: SEL 18 mg + CILO 30 mg (Non-cirrhotic)	10
Cohort 5: SEL 18 mg + FIR 20 mg (Non-cirrhotic)	20
Cohort 6: CILO 30 mg + FIR 20 mg (Non-cirrhotic)	10
Cohort 7: CILO 20 mg (Cirrhotic)	40
Cohort 8: CILO 30 mg (Cirrhotic)	30
Cohort 9: SEL 18 mg + FIR 20 mg + CILO 30 mg (Non-cirrhotic)	15.4
Cohort 10: FIR 20 mg + FENO 48 mg	6.7
Cohort 11: FIR 20 mg + FENO 145 mg	12.5
Cohort 12: FIR 20 mg + CILO 30 mg + VAS 2g	6.7
Cohort 13: FIR 20 mg + CILO 30 mg + FENO 145 mg	6.3

"A treatment emergent serious adverse event (SAE) was defined as an event that, at any dose, results in the following:~Death~Life-threatening~In-patient hospitalization or prolongation of existing hospitalization~Persistent or significant disability/incapacity~A congenital anomaly/birth defect~A medically important event or reaction" (NCT02781584)
Timeframe: Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.

Percentage of Participants Who Experienced Treatment-Emergent Adverse Events

Intervention	percentage of participants (Number)
Cohort 1: SEL 18 mg (Non-cirrhotic)	0
Cohort 2: FIR 20 mg (Non-cirrhotic)	0
Cohort 3: CILO 30 mg (Non-cirrhotic)	0
Cohort 4: SEL 18 mg + CILO 30 mg (Non-cirrhotic)	5
Cohort 5: SEL 18 mg + FIR 20 mg (Non-cirrhotic)	5
Cohort 6: CILO 30 mg + FIR 20 mg (Non-cirrhotic)	5
Cohort 7: CILO 20 mg (Cirrhotic)	10
Cohort 8: CILO 30 mg (Cirrhotic)	0
Cohort 9: SEL 18 mg + FIR 20 mg + CILO 30 mg (Non-cirrhotic)	7.69
Cohort 10: FIR 20 mg + FENO 48 mg	0
Cohort 11: FIR 20 mg + FENO 145 mg	0
Cohort 12: FIR 20 mg + CILO 30 mg + VAS 2g	3.33
Cohort 13: FIR 20 mg + CILO 30 mg + FENO 145 mg	3.12

"Treatment-emergent AEs were defined as events that met 1 or both of the following criteria:~Any AEs with onset dates on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug~Any AEs leading to premature discontinuation of study drug" (NCT02781584)
Timeframe: Cohorts 1-9: First dose date up to 12 weeks plus 30 days; Cohorts 10-11: First dose date up to 26 weeks plus 30 days; Cohorts 12-13: First dose date up to 8 weeks plus 30 days. For Cohorts 10-13, the first dose date included the Pre-treatment Phase.

Article	Year
The Race to Bash NASH: Emerging Targets and Drug Development in a Complex Liver Disease. Journal of medicinal chemistry, 2020, 05-28, Volume: 63, Issue:10 Topics: Animals; Anticholesteremic Agents; Drug Delivery Systems; Drug Development; Humans; Hypoglycemic Age	2020
Impact of fenofibrate on NAFLD/NASH: A genetic perspective. Drug discovery today, 2022, Volume: 27, Issue:8 Topics: Fenofibrate; Hepatocytes; Humans; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease	2022
Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. The Cochrane database of systematic reviews, 2013, Dec-27, Issue:12 Topics: Alanine Transaminase; Atorvastatin; Fatty Liver; Fenofibrate; gamma-Glutamyltransferase; Heptanoic A	2013
New peroxisome proliferator-activated receptor agonists: potential treatments for atherogenic dyslipidemia and non-alcoholic fatty liver disease. Expert opinion on pharmacotherapy, 2014, Volume: 15, Issue:4 Topics: Acetates; Animals; Atherosclerosis; Chalcones; Cholesterol, HDL; Dyslipidemias; Fatty Liver; Fenofib	2014

Article	Year
Omega-3 carboxylic acids and fenofibrate differentially alter plasma lipid mediators in patients with non-alcoholic fatty liver disease. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2021, Volume: 35, Issue:11 Topics: Adult; Aged; Carboxylic Acids; Fatty Acids, Omega-3; Female; Fenofibrate; Humans; Hypertriglyceridem	2021
Fenofibrate Mitigates Hypertriglyceridemia in Nonalcoholic Steatohepatitis Patients Treated With Cilofexor/Firsocostat. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2023, Volume: 21, Issue:1 Topics: Acetyl-CoA Carboxylase; Fenofibrate; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Liver Cirrh	2023
Comparison of fenofibrate and pioglitazone effects on patients with nonalcoholic fatty liver disease. European journal of gastroenterology & hepatology, 2017, Volume: 29, Issue:12 Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Blood Pressure; Body Mass Index; Diet; Exe	2017
Comparative clinical study between the effect of fenofibrate alone and its combination with pentoxifylline on biochemical parameters and liver stiffness in patients with non-alcoholic fatty liver disease. Hepatology international, 2015, Volume: 9, Issue:3 Topics: Adult; Blood Glucose; Drug Therapy, Combination; Female; Fenofibrate; Humans; Hyaluronic Acid; Hypol	2015
Opposite associations between alanine aminotransferase and γ-glutamyl transferase levels and all-cause mortality in type 2 diabetes: Analysis of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Metabolism: clinical and experimental, 2016, Volume: 65, Issue:5 Topics: Aged; Alanine Transaminase; Australia; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus, Type	2016

Article	Year
Synthesis of natural 3'-Prenylchalconaringenin and biological evaluation of ameliorating non-alcoholic fatty liver disease and metabolic syndrome. European journal of medicinal chemistry, 2020, Nov-01, Volume: 205 Topics: 3T3-L1 Cells; AMP-Activated Protein Kinases; Animals; Chalcones; Chemistry Techniques, Synthetic; He	2020
Establishment of an Adult Medaka Fatty Liver Model by Administration of a Gubra-Amylin-Nonalcoholic Steatohepatitis Diet Containing High Levels of Palmitic Acid and Fructose. International journal of molecular sciences, 2021, Sep-14, Volume: 22, Issue:18 Topics: Animals; Body Weight; Diet, High-Fat; Disease Models, Animal; Female; Fenofibrate; Fructose; Gene Ex	2021
Hepatic eLife, 2021, 12-29, Volume: 10 Topics: Animals; Female; Fenofibrate; Humans; Hypolipidemic Agents; Lipid Metabolism; Male; Mice; MicroRNAs;	2021
Target Deconvolution of Fenofibrate in Nonalcoholic Fatty Liver Disease Using Bioinformatics Analysis. BioMed research international, 2021, Volume: 2021 Topics: Computational Biology; Fenofibrate; Humans; Liver; Liver Cirrhosis; Metabolic Diseases; Non-alcoholi	2021
Functional and Structural Insights into Human PPARα/δ/γ Subtype Selectivity of Bezafibrate, Fenofibric Acid, and Pemafibrate. International journal of molecular sciences, 2022, Apr-25, Volume: 23, Issue:9 Topics: Benzoxazoles; Bezafibrate; Butyrates; Diabetes Mellitus, Type 2; Dyslipidemias; Fenofibrate; Humans;	2022
Combinations of an acetyl CoA carboxylase inhibitor with hepatic lipid modulating agents do not augment antifibrotic efficacy in preclinical models of NASH and fibrosis. Hepatology communications, 2022, Volume: 6, Issue:9 Topics: Acetates; Acetyl-CoA Carboxylase; Animals; Fenofibrate; Humans; Hypertriglyceridemia; Liver Cirrhosi	2022
Peroxisomal Fitness: A Potential Protective Mechanism of Fenofibrate against High Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice. Diabetes & metabolism journal, 2022, Volume: 46, Issue:6 Topics: Animals; Chemical and Drug Induced Liver Injury, Chronic; Diet, High-Fat; Fatty Acids; Fenofibrate;	2022
Daily Intake of Smallanthus sonchifolius (Yacon) Roots Reduces the Progression of Non-alcoholic Fatty Liver in Rats Fed a High Fructose Diet. Plant foods for human nutrition (Dordrecht, Netherlands), 2022, Volume: 77, Issue:4 Topics: Actins; Animals; Asteraceae; Diet; Fenofibrate; Fructose; Inflammation; Insulin; Lipids; Liver; Non-	2022
Capparis spinosa improves non-alcoholic steatohepatitis through down-regulating SREBP-1c and a PPARα-independent pathway in high-fat diet-fed rats. BMC research notes, 2022, Oct-03, Volume: 15, Issue:1 Topics: Acetyl-CoA Carboxylase; Animals; Capparis; Carnitine O-Palmitoyltransferase; Diet, High-Fat; Fenofib	2022
Engineered Fenofibrate as Oxidation-Sensitive Nanoparticles with ROS Scavenging and PPARα-Activating Bioactivity to Ameliorate Nonalcoholic Fatty Liver Disease. Molecular pharmaceutics, 2023, 01-02, Volume: 20, Issue:1 Topics: Animals; Fenofibrate; Hydrogen Peroxide; Liver; Mice; Mice, Inbred C57BL; Nanoparticles; Non-alcohol	2023
Down-regulation of hepatic CLOCK by PPARα is involved in inhibition of NAFLD. Journal of molecular medicine (Berlin, Germany), 2023, Volume: 101, Issue:1-2 Topics: Animals; Diet, High-Fat; Down-Regulation; Fenofibrate; Lipid Metabolism; Lipids; Liver; Male; Mice;	2023
Down-regulation of hepatic CLOCK by PPARα is involved in inhibition of NAFLD. Journal of molecular medicine (Berlin, Germany), 2023, Volume: 101, Issue:1-2 Topics: Animals; Diet, High-Fat; Down-Regulation; Fenofibrate; Lipid Metabolism; Lipids; Liver; Male; Mice;	2023
Down-regulation of hepatic CLOCK by PPARα is involved in inhibition of NAFLD. Journal of molecular medicine (Berlin, Germany), 2023, Volume: 101, Issue:1-2 Topics: Animals; Diet, High-Fat; Down-Regulation; Fenofibrate; Lipid Metabolism; Lipids; Liver; Male; Mice;	2023
Down-regulation of hepatic CLOCK by PPARα is involved in inhibition of NAFLD. Journal of molecular medicine (Berlin, Germany), 2023, Volume: 101, Issue:1-2 Topics: Animals; Diet, High-Fat; Down-Regulation; Fenofibrate; Lipid Metabolism; Lipids; Liver; Male; Mice;	2023
Acetyl-CoA carboxylase inhibitor increases LDL-apoB production rate in NASH with cirrhosis: prevention by fenofibrate. Journal of lipid research, 2023, Volume: 64, Issue:3 Topics: Acetyl-CoA Carboxylase; Apolipoproteins B; Cholesterol, LDL; Fenofibrate; Humans; Liver Cirrhosis; N	2023
Fenofibrate improves hepatic steatosis, insulin resistance, and shapes the gut microbiome via TFEB-autophagy in NAFLD mice. European journal of pharmacology, 2023, Dec-05, Volume: 960 Topics: Animals; Autophagy; Diet, High-Fat; Fenofibrate; Gastrointestinal Microbiome; Insulin Resistance; Li	2023
Simultaneous co-assembly of fenofibrate and ketoprofen peptide for the dual-targeted treatment of nonalcoholic fatty liver disease (NAFLD). Chemical communications (Cambridge, England), 2020, May-04, Volume: 56, Issue:36 Topics: Fenofibrate; Humans; Inflammation; Ketoprofen; Lipid Metabolism; Molecular Structure; Non-alcoholic	2020
Protective effect of fenofibrate against high-fat-high-fructose diet induced non-obese NAFLD in rats. Fundamental & clinical pharmacology, 2021, Volume: 35, Issue:2 Topics: Animals; Dietary Sugars; Fenofibrate; Fructose; Hypolipidemic Agents; Male; Non-alcoholic Fatty Live	2021
Amelioration of diet-induced steatohepatitis in mice following combined therapy with ASO-Fsp27 and fenofibrate. Journal of lipid research, 2017, Volume: 58, Issue:11 Topics: Animals; Diet; Drug Synergism; Fenofibrate; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Live	2017
Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models. Liver international : official journal of the International Association for the Study of the Liver, 2018, Volume: 38, Issue:6 Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Biomarkers; Diet, High-Fat; Fenofibrate;	2018
Polyurethane Nanoparticle-Loaded Fenofibrate Exerts Inhibitory Effects on Nonalcoholic Fatty Liver Disease in Mice. Molecular pharmaceutics, 2018, 10-01, Volume: 15, Issue:10 Topics: Animals; Drug Carriers; Fenofibrate; Hep G2 Cells; Humans; Hypolipidemic Agents; Liver; Male; Methio	2018
[Effects of sera of rats fed with Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 2018, Nov-30, Volume: 38, Issue:11 Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Disease Models, Animal; Drugs, Chinese H	2018
APOE3Leiden.CETP transgenic mice as model for pharmaceutical treatment of the metabolic syndrome. Diabetes, obesity & metabolism, 2014, Volume: 16, Issue:6* Topics: 11-beta-Hydroxysteroid Dehydrogenase Type 1; Animals; Apolipoprotein E3; Atorvastatin; Cholesterol E	2014
Beneficial effects of neomangiferin on high fat diet-induced nonalcoholic fatty liver disease in rats. International immunopharmacology, 2015, Volume: 25, Issue:1 Topics: Amino Acid Transport System ASC; Animals; Body Weight; Carnitine O-Palmitoyltransferase; Cholesterol	2015
Effect of oleoylethanolamide on diet-induced nonalcoholic fatty liver in rats. Journal of pharmacological sciences, 2015, Volume: 127, Issue:3 Topics: Animals; Diet, High-Fat; Endocannabinoids; Fatty Acids; Fenofibrate; Hep G2 Cells; Humans; Hypolipid	2015
Fenofibrate treatment attenuated chronic endoplasmic reticulum stress in the liver of nonalcoholic fatty liver disease mice. Pharmacology, 2015, Volume: 95, Issue:3-4 Topics: Animals; Apoptosis; Blood Glucose; Cholesterol; Endoplasmic Reticulum Chaperone BiP; Endoplasmic Ret	2015
PPARα/γ agonists and antagonists differently affect hepatic lipid metabolism, oxidative stress and inflammatory cytokine production in steatohepatitic rats. Cytokine, 2015, Volume: 75, Issue:1 Topics: Anilides; Animals; Chemokine CCL2; Cytokines; Disease Models, Animal; Fatty Acids, Nonesterified; Fe	2015
[Effects of fenofibrate on hepatocyte apoptosis in nonalcoholic fatty liver]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology, 2015, Volume: 23, Issue:9 Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Caspase 3; Diet, High-Fat; Fenofibrate; Hepatocytes;	2015
Effects of combined PPAR-γ and PPAR-α agonist therapy on fructose induced NASH in rats: Modulation of gene expression. European journal of pharmacology, 2016, Feb-15, Volume: 773 Topics: Adiponectin; Adipose Tissue; Animals; Blood Glucose; Body Weight; Dose-Response Relationship, Drug;	2016
Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. Gut, 2016, Volume: 65, Issue:7 Topics: Adipocytes; Aging; Animals; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Disease Models	2016
Resveratrol and fenofibrate ameliorate fructose-induced nonalcoholic steatohepatitis by modulation of genes expression. World journal of gastroenterology, 2016, Mar-14, Volume: 22, Issue:10 Topics: Animals; Disease Models, Animal; Drug Therapy, Combination; Energy Metabolism; Fenofibrate; Fructose	2016
[Role and mechanism of action of fibroblast growth factor-21 in reducing triglyceride in nonalcoholic fatty liver disease]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology, 2016, Volume: 24, Issue:2 Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Cell Line; Diet, High-Fat; Disease Model	2016
Fenofibrate nanoliposome: Preparation and its inhibitory effects on nonalcoholic fatty liver disease in mice. Nanomedicine : nanotechnology, biology, and medicine, 2016, Volume: 12, Issue:8 Topics: Animals; Choline; Fenofibrate; Hypolipidemic Agents; Liposomes; Liver; Methionine; Mice; Nanoparticl	2016
The effects of herbal composition Gambigyeongsinhwan (4) on hepatic steatosis and inflammation in Otsuka Long-Evans Tokushima fatty rats and HepG2 cells. Journal of ethnopharmacology, 2017, Jan-04, Volume: 195 Topics: Alanine Transaminase; Animals; Anti-Inflammatory Agents; Biomarkers; Cytokines; Disease Models, Anim	2017
Potential involvement of PPAR α activation in diminishing the hepatoprotective effect of fenofibrate in NAFLD: Accuracy of non- invasive panel in determining the stage of liver fibrosis in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2017, Volume: 85 Topics: Animals; Body Weight; Fenofibrate; Gene Expression Regulation; Glomerular Filtration Rate; Hypolipid	2017
[Effect of Hugan Qingzhi tablets on AMPK pathway activation and NF-κB-p65 protein expression in the liver of rats with nonalcoholic fatty liver disease]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University, 2017, 01-20, Volume: 37, Issue:1 Topics: AMP-Activated Protein Kinases; Animals; Cytokines; Diet, High-Fat; Drugs, Chinese Herbal; Fenofibrat	2017
Fenofibrate, but not ezetimibe, prevents fatty liver disease in mice lacking phosphatidylethanolamine Journal of lipid research, 2017, Volume: 58, Issue:4 Topics: Animals; Disease Models, Animal; Endoplasmic Reticulum Stress; Ezetimibe; Fenofibrate; Humans; Insul	2017
Peroxisome proliferator-activated receptor-alpha gene level differently affects lipid metabolism and inflammation in apolipoprotein E2 knock-in mice. Arteriosclerosis, thrombosis, and vascular biology, 2011, Volume: 31, Issue:7 Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents; Aorta; Apolipoprotein E2; Atherosclerosis;	2011
PPARα activation differently affects microparticle content in atherosclerotic lesions and liver of a mouse model of atherosclerosis and NASH. Atherosclerosis, 2011, Volume: 218, Issue:1 Topics: Animals; Atherosclerosis; Biomarkers; Cell-Derived Microparticles; Disease Models, Animal; Fatty Liv	2011
Adiponectin reduces connective tissue growth factor in human hepatocytes which is already induced in non-fibrotic non-alcoholic steatohepatitis. Experimental and molecular pathology, 2011, Volume: 91, Issue:3 Topics: Adiponectin; Anticholesteremic Agents; Connective Tissue Growth Factor; Down-Regulation; Fatty Liver	2011

fenofibrate and Fatty Liver, Nonalcoholic