[Translation] A multicenter, randomized, double-blind, parallel controlled clinical trial to evaluate the safety and efficacy of oral taremide sodium tablets in patients with systemic lupus erythematosus

1.探索口服不同剂量泰瑞米特钠片多次给药条件下，用于治疗系统性红斑狼疮患者的安全性及有效性 2.探索稳态血药浓度及体内暴露量 3.探索系统性红斑狼疮的相关药效动力学（PD）生物标记物 4.为III期临床试验确定给药方案和用药剂量提供依据

[Translation]

1. To explore the safety and efficacy of oral taremide sodium tablets at different doses for the treatment of patients with systemic lupus erythematosus under multiple administration conditions 2. To explore the steady-state blood drug concentration and in vivo exposure 3. To explore the relevant pharmacodynamic (PD) biomarkers of systemic lupus erythematosus 4. To provide a basis for determining the dosing regimen and dosage for Phase III clinical trials

Start Date14 May 2019

Sponsor / Collaborator

Suzhou Changzheng Cinkate Pharmaceutical Co., Ltd.

[+2]

CTR20150314 / CompletedPhase 1

泰瑞米特钠片与来氟米特片的口服相对生物利用度研究

[Translation] Study on the relative oral bioavailability of teremide sodium tablets and leflunomide tablets

1）研究健康受试者单次口服泰瑞米特钠片和来氟米特片后血浆泰瑞米特浓度的经时过程和尿中泰瑞米特及其代谢产物的排泄量，以此确定泰瑞米特的药代动力学特征，为确定泰瑞米特钠片的临床使用剂量提供依据；2）评价泰瑞米特钠片与来氟米特片的口服相对生物利用度；3）评价单次口服泰瑞米特钠片和来氟米特片后的安全性和耐受性。

[Translation]

1) To study the time course of plasma tetamide concentration and urinary excretion of tetamide and its metabolites in healthy subjects after a single oral administration of tetamide sodium tablets and leflunomide tablets, so as to determine the pharmacokinetic characteristics of tetamide and provide a basis for determining the clinical dosage of tetamide sodium tablets; 2) To evaluate the oral relative bioavailability of tetamide sodium tablets and leflunomide tablets; 3) To evaluate the safety and tolerability of tetamide sodium tablets and leflunomide tablets after a single oral administration.

Start Date27 May 2015

Sponsor / Collaborator

Suzhou Changzheng Cinkate Pharmaceutical Co., Ltd.

[+2]

100 Clinical Results associated with Teriflunomide Sodium

100 Translational Medicine associated with Teriflunomide Sodium

100 Patents (Medical) associated with Teriflunomide Sodium

Literatures (Medical) associated with Teriflunomide Sodium

01 Aug 2019·European Journal of Pharmaceutical Sciences

A population pharmacokinetic study to accelerate early phase clinical development for a novel drug, teriflunomide sodium, to treat systemic lupus erythematosus

Article

Author: Chen, Xia ; Hu, Pei ; Yao, Xueting ; Jiang, Ji ; Wu, Yiwen ; Liu, Dongyang

PURPOSETo accelerate early phase clinical development of a novel drug, teriflunomide sodium, to treat systemic lupus erythematosus (SLE) based on the data of leflunomide.METHODSBased on a pharmacokinetic (PK) study assessing the relative bioavailability of teriflunomide sodium compared to leflunomide, a population pharmacokinetic (Pop PK) analysis was firstly conducted using non-linear mixed effect model. Covariates were thoughtfully screened after Pop PK model evaluation and qualification using various diagnostic plots, visual predicted check (VPC) and bootstrap method. In order to predict teriflunomide PK profiles for multiple dosing of teriflunomide sodium in SLE patients, a model integrating enterohepatic circulation (EHC) mechanism was utilized to simulate the teriflunomide PK profile after multiple dosing of 20 mg/day leflunomide, and compare it to the teriflunomide PK profile in a 20 mg/day leflunomide multiple dose study in rheumatoid arthritis patients. Validated EHC PK model was applied to optimize dose regimen for teriflunomide sodium in SLE patients.RESULTSA population one-compartment model with pulsed EHC characteristic was developed to capture teriflunomide PK profiles after administration of leflunomide and teriflunomide sodium. Body weight and male sex were found to significantly increase apparent volume of central compartment. ABCG2 34G>A polymorphism was found to significantly change apparent clearance and absorption rate. The Pop PK model was evaluated and validated. After this model was confirmed to capture EHC characteristics of teriflunomide in both healthy subjects and patients with rheumatoid arthritis after single and multiple dosing leflunomide, it was applied to suggest dose regimen of teriflunomide sodium in phase II study.CONCLUSIONSThe pulsed EHC Pop PK model characterized the teriflunomide PK processes well in both healthy subjects and patients. Body weight, sex, and ABCG2 34G>A genotype were identified to significantly affect PK characteristics. The developed EHC Pop PK model exhibited the ability to predict PK profiles of teriflunomide in patients after long-term dosing and could be utilized to support phase II trial design.

01 Jul 2019·Clinical Drug InvestigationQ4 · MEDICINE

Safety, Pharmacokinetics, and Pharmacogenetics of Single-Dose Teriflunomide Sodium and Leflunomide in Healthy Chinese Subjects

Q4 · MEDICINE

Article

Author: Yao, Xueting ; Wu, Yiwen ; Hu, Pei ; Liu, Dongyang ; Jiang, Ji ; Chen, Xia

BACKGROUNDTeriflunomide sodium, a novel derivative of leflunomide, was developed to treat systemic lupus erythematosus.OBJECTIVEThe objectives of this trial were to study the safety, pharmacokinetics, and pharmacogenetics of teriflunomide sodium in healthy Chinese subjects in order to support its accelerated development.METHODSA clinical study was designed as a single-dose, randomized, parallel, open-label study. Healthy volunteers were randomly assigned to take teriflunomide sodium 10 mg or leflunomide 10 mg. Eligible healthy volunteers were monitored over a 98-day observation period. Blood and urine samples were collected and analyzed for teriflunomide and its metabolite concentrations, and ABCG2 and CYP2C9 genotypes were detected. The safety profile was also collected.RESULTSAll adverse events were mild in intensity, and all subjects completed this trial without any other treatment. After a single administration of teriflunomide sodium and leflunomide, teriflunomide maximal concentrations were 1.32 ± 0.341 mg/L and 0.718 ± 0.169 mg/L, and area under the concentration-time curve from time zero to infinity (AUC_∞) was 423 ± 229 mg·h/L and 303 ± 159 mg·h/L, respectively. Overall, teriflunomide AUC_∞ in ABCG2 34A/A mutants was 70.4% lower than in wild-type ABCG2 34G/G after administration of teriflunomide sodium. In addition, after administration of leflunomide, teriflunomide AUC_∞ in ABCG2 34A/A mutants was 30.0% lower than in subjects carrying ABCG2 34G/G.CONCLUSIONSTeriflunomide sodium was generally safe and well tolerated in healthy Chinese subjects. The relative bioavailability of teriflunomide between teriflunomide sodium and leflunomide after a single dose administration was approximately 150%. Additionally, ABCG2 34G>A was found to significantly affect teriflunomide pharmacokinetics, which suggested ABCG2 34G>A may be a significant influencing factor.CLINICAL TRIAL REGISTRATIONThis study was registered at the China National Medical Products Administration ( http://www.nmpa.gov.cn ; registration number 2014L01935), and also at the China platform for registry and publicity of drug clinical trials ( http://www.chinadrugtrials.org.cn ; registration number CTR20150314).

01 Mar 2019·Biomedical ChromatographyQ4 · MEDICINE

Development of a simple HPLC–MS/MS method to simultaneously determine teriflunomide and its metabolite in human plasma and urine: Application to clinical pharmacokinetic study of teriflunomide sodium and leflunomide

Q4 · MEDICINE

Article

Author: Yao, Xueting ; Jiang, Ji ; Hu, Pei ; Song, Ling ; Xiao, Fei ; Liu, Dongyang ; Liu, Yang

AbstractA simple high‐performance liquid chromatography coupled with tandem mass spectrometry method was developed and fully validated to simultaneously determine teriflunomide (TER) and its metabolite 4‐trifluoro‐methylaniline oxanilic acid (4‐TMOA) in human plasma and urine. Merely 50 μL plasma and 20 μL urine were employed in sample preparation using protein precipitation and direct dilution method, respectively. An Agilent Zorbax eclipse plus C18 column was selected to achieve rapid separation for TER and 4‐TMOA within 3 min. Electrospray ionization under multiple reaction monitoring was used to monitor the ion transitions for TER (m/z 269.0 → 159.9), 4‐TMOA (m/z 231.9 → 160.0), internal standard teriflunomide‐d4 (m/z 273.0 → 164.0) and 2‐amino‐4‐trifluoromethyl benzoic acid (m/z 203.8 → 120.1), operating in the negative ion mode. This method proved to have better accuracy and precision over concentration range of 10–5000 ng/mL in plasma as well as 10–10,000 ng/mL in urine. After a full validation, this method was successfully applied in a pharmacokinetic study of teriflunomide sodium and leflunomide in Chinese healthy volunteers.

100 Deals associated with Teriflunomide Sodium

R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Systemic Lupus Erythematosus	Phase 2	CN	Xinkaiyiyao Science & Technology Shanghai Co. Ltd.	14 May 2019
Systemic Lupus Erythematosus	Phase 2	CN	Xinkai Medicine and Chemical Intermediates (Shanghai) Co., Ltd.	14 May 2019

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