Primary objective: To compare the pharmacokinetic characteristics of flufenidone capsules in subjects with mild hepatic impairment and subjects with normal hepatic function. Secondary objective: To evaluate the safety of flufenidone capsules in subjects with hepatic impairment.

Start Date18 Mar 2022

Sponsor / Collaborator

Haikou Pharmaceutical Co. Ltd.

[+1]

CTR20211557 / Active, not recruitingPhase 2

以富马酸丙酚替诺福韦片作为基础治疗，评估不同剂量的氟非尼酮胶囊治疗慢性乙型病毒性肝炎肝纤维化的有效性和安全性的多中心、随机、双盲、安慰剂、平行对照 II 期临床试验

[Translation] A multicenter, randomized, double-blind, placebo-controlled, parallel-controlled phase II clinical trial to evaluate the efficacy and safety of different doses of flufenidone capsules in the treatment of liver fibrosis in chronic hepatitis B using tenofovir alafenamide fumarate tablets as the basic treatment

主要目的：与安慰剂对照，初步评价不同剂量氟非尼酮胶囊治疗慢性乙型病毒性肝炎肝纤维化的有效性。次要目的：初步评价不同剂量氟非尼酮胶囊治疗慢性乙型病毒性肝炎肝纤维化的安全性。

[Translation]

Primary objective: To preliminarily evaluate the effectiveness of different doses of flufenidone capsules in the treatment of liver fibrosis caused by chronic hepatitis B virus infection compared with placebo. Secondary objective: To preliminarily evaluate the safety of different doses of flufenidone capsules in the treatment of liver fibrosis caused by chronic hepatitis B virus infection.

Start Date22 Nov 2021

Sponsor / Collaborator

Haikou Pharmaceutical Co. Ltd.

[+1]

CTR20211372 / CompletedNot Applicable

富马酸丙酚替诺福韦片对氟非尼酮胶囊的药代动力学影响试验

[Translation] Effect of tenofovir alafenamide fumarate tablets on the pharmacokinetics of flufenidone capsules

主要目的：评价富马酸丙酚替诺福韦片对中国健康成人受试者餐后状态下口服氟非尼酮胶囊药代动力学的影响。次要研究目的：评价中国健康成人受试者餐后状态下单独口服氟非尼酮胶囊、随餐单独服用富马酸丙酚替诺福韦片或餐后状态下同时服用富马酸丙酚替诺福韦片和氟非尼酮时的安全性。

[Translation]

Primary objective: To evaluate the effect of tenofovir alafenamide fumarate tablets on the pharmacokinetics of flufenidone capsules in healthy Chinese adult subjects after meals. Secondary objective: To evaluate the safety of flufenidone capsules alone in healthy Chinese adult subjects after meals, taking tenofovir alafenamide fumarate tablets alone with meals, or taking tenofovir alafenamide fumarate tablets and flufenidone at the same time after meals.

Start Date06 Jul 2021

Sponsor / Collaborator

Haikou Pharmaceutical Co. Ltd.

[+1]

100 Clinical Results associated with Fluorofenidone

100 Translational Medicine associated with Fluorofenidone

100 Patents (Medical) associated with Fluorofenidone

Literatures (Medical) associated with Fluorofenidone

01 Dec 2023·Cell biochemistry and biophysics

Fluorofenidone Attenuates Renal Interstitial Fibrosis by Enhancing Autophagy and Retaining Mitochondrial Function.

Article

Author: Lu, Miaomiao ; Zhou, Hongli ; Liu, Wenlin ; Xing, Di ; Dong, Haonan

BACKGROUNDFluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood.METHODSA renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5'-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM.RESULTSCompared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iβ and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages.CONCLUSIONThe results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway.

01 Nov 2023·Biochemical and Biophysical Research Communications

Fluorofenidone enhances cardiac contractility by stimulating CICR and CaV1.2

Article

Author: Ávila, Guillermo

Fluorofenidone (AKF-PD) is a novel pyridone derivative that inhibits fibrosis and inflammation in many tissues. Accordingly, it has been effective in disease models, such as liver failure, nephropathy, and pulmonary fibrosis. However, its potential role in cardiac physiology and pathology has yet to be elucidated. Thus, this paper investigated a possible functional impact of AKF-PD on adult rat cardiac myocytes. Cells were kept in culture for 1-2 days under either control conditions or the presence of AKF-PD (500 μM). They were next examined concerning cell contractility, intracellular Ca²⁺ homeostasis, and activity of voltage-gated Ca²⁺ channels. Remarkably, AKF-PD enhanced the percentage of cell shortening and rates of both contraction and relaxation by nearly 100%. A stimulus in Ca²⁺-induced Ca²⁺ release (CICR) most likely accounts for these effects because AKF-PD also increased the magnitude of electrically evoked Ca²⁺ transients. Of note, the compound did not alter the peak value of caffeine-elicited Ca²⁺ transients, indicating stimulation of CICR at constant sarcoplasmic reticulum Ca²⁺ load. Since CICR is triggered by the entry of Ca²⁺ through Ca_V1.2 (I_Ca), a possible effect on these Ca²⁺ channels was also investigated. AKF-PD increased the magnitude of both I_Ca and maximal macroscopic Ca²⁺ conductance (G_max) by about 50%. However, no differences were found in either voltage dependence of inactivation or the amount of maximal immobilization-resistant charge movement (Q_max). Thus, the effect on I_Ca could be explained by a higher channel's open probability (P_o) rather than a greater abundance of channel proteins. Additional data indicate that AKF-PD reduces the rate of Ca²⁺ extrusion in the presence of caffeine, suggesting inhibition of the Na/Ca exchanger. Overall, these results indicate that AKF-PD upregulates the P_o of Ca_V1.2 and then sequentially enhances I_Ca, CICR, and contractility. Therefore, the novel compound is also a candidate to be tested in cardiac disease models.

04 Sep 2023·Molecular pharmaceutics

Complexation of Fluorofenidone by Cucurbit[7]uril and β-Cyclodextrin: Keto-Enol Tautomerization to Enhance the Solubility.

Article

Author: Lu, Tong-Bu ; Chen, Hua-Yu ; Huang, Yong-Liang ; Chen, Jia-Mei ; Ma, Wen-Juan

This study is designed to compare drug encapsulation by cucurbit[7]uril and β-cyclodextrin, using fluorofenidone as a model drug. Single-crystal X-ray diffraction analysis was employed to successfully determine the crystal structures of fluorofenidone·H⁺@cucurbit[7]uril Form, fluorofenidone@cucurbit[7]uril Form, and fluorofenidone@β-cyclodextrin Form. Keto-enol tautomerization of fluorofenidone mediated by cucurbit[7]uril in acid solution is confirmed by crystal structures, pH titration, and nuclear magnetic resonance experiments. However, β-cyclodextrin cannot cause the keto-enol tautomerization of fluorofenidone under similar conditions. The phase solubility study demonstrates that cucurbit[7]uril has a much higher solubilization capacity for fluorofenidone than β-cyclodextrin in 0.1 M HCl since the K_c values of fluorofenidone with cucurbit[7]uril and β-cyclodextrin were 1223.97 ± 452.68 and 78.49 ± 10.56 M^-1, respectively. Excellent solubility can be attributed to the keto-enol tautomerization of fluorofenidone under the conditions of cucurbit[7]uril in acid solution. The enol form of fluorofenidone is encapsulated by cucurbit[7]uril by hydrogen bonding interaction and hydrophobic interaction to increase binding affinity. Rat pharmacokinetic studies demonstrate that the area under the plasma concentration-time curve from time 0 to 7 h value of fluorofenidone@cucurbit[7]uril complex is 1.70-fold greater than that of free fluorofenidone, and the mean residence time from time 0 to 7 h is slightly prolonged from 1.29 to 1.76 h (P < 0.01) after oral administration. However, no significant difference is found between fluorofenidone and fluorofenidone@β-cyclodextrin complex. This work indicates that the induction of keto-enol tautomerization of drugs using macrocyclic molecules has the potential to be an effective method to improve their solubility and bioavailability, providing valuable insights for the application of macrocyclic molecules in the biomedical field.

100 Deals associated with Fluorofenidone

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Fibrosis, Liver	Phase 2	CN	Central South University	22 Nov 2021
Fibrosis, Liver	Phase 2	CN	Haikou Pharmaceutical Co. Ltd.	22 Nov 2021
Hepatitis B, Chronic	Phase 2	CN	Haikou Pharmaceutical Co. Ltd.	22 Nov 2021
Hepatitis B, Chronic	Phase 2	CN	Central South University	22 Nov 2021
Renal fibrosis	Phase 1	CN	Hainan Haiyao Co., Ltd.	-
Renal fibrosis	Phase 1	CN	Central South University	-
Renal fibrosis	Phase 1	CN	Dierepharma HK Ltd	-
Liver Cirrhosis	Preclinical	CN	Haikou Pharmaceutical Co. Ltd.	19 Nov 2018
Liver Cirrhosis	Discovery	CN	Central South University	19 Nov 2018

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