janagliflozin / Sihuan Pharmaceutical - LARVOL DELTA

Pharmacokinetics, Pharmacodynamics and Safety of Janagliflozin in Chinese Type 2 Diabetes Mellitus Patients with Renal Impairment. (PubMed, Clin Pharmacokinet) - "The exposure levels of janagliflozin in T2DM patients were slightly increased with worsening of RI (i.e., 11% increase in the AUC in patients with moderate RI compared with the normal renal function group). Despite worsening of renal function, janagliflozin exerted a significant pharmacologic effect and was well tolerated, even in patients with moderate RI, implying a promising role in the treatment of patients with in T2DM."

Journal • PK/PD data • Diabetes • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

A Model-Informed Approach to Accelerate the Clinical Development of Janagliflozin, an Innovative SGLT2 Inhibitor. (PubMed, Clin Pharmacokinet) - "The application of MIDD strategy adequately supported the decision making at each stage of janagliflozin development process. A waiver of Phase 2 study was successfully approved for janagliflozin based on these model-informed results and suggestions. This MIDD strategy of janagliflozin could be further utilized to support the clinical development of other SGLT2 inhibitors."

Clinical • Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Efficacy and Safety of Janagliflozin Monotherapy in Chinese Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Diet and Exercise: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 3 Trial. (PubMed, Diabetes Obes Metab) - P3 | "Janagliflozin 25 mg and 50 mg monotherapy once-daily effectively improved glycemic control, reduced body weight and blood pressure, improved HDL-C and insulin sensitivity, and was generally well-tolerated."

Clinical • Journal • Monotherapy • P3 data • Diabetes • Infectious Disease • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Efficacy and Safety of Janagliflozin as Add-on Therapy to Metformin in Chinese Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin Alone: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 3 Trial. (PubMed, Diabetes Obes Metab) - "Janagliflozin 25 mg or 50 mg once-daily added to metformin therapy significantly improved glycemic control, reduced body weight and SBP, improved HDL-C and insulin sensitivity, and was generally well-tolerated by Chinese T2DM patients who had poor glycemic control with metformin monotherapy."

Clinical • Journal • P3 data • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Prediction of Janagliflozin Pharmacokinetics in Type 2 Diabetes Mellitus Patients with Liver Cirrhosis or Renal Impairment Using a Physiologically Based Pharmacokinetic Model. (PubMed, Eur J Pharm Sci) - "Dose adjustment is less critical for these patients. Risk benefit assessment in janagliflozin dosing for T2DM patients with liver disease is recommended."

Journal • PK/PD data • Diabetes • Fibrosis • Gastroenterology • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Renal Disease • Type 2 Diabetes Mellitus

Pharmacokinetics, Pharmacodynamics, and Tolerability of Single- and Multiple-Doses of Janagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, in Chinese Subjects with Type 2 Diabetes Mellitus. (PubMed, Diabetes Obes Metab) - "Single and multiple oral administration (14 days) of janagliflozin 25 mg and 50 mg exhibited favorable PK, PD, and tolerability profiles in Chinese subjects with T2DM, and were comparable to dapagliflozin 10 mg. Janagliflozin 25 mg and 50 mg are recommended for further clinical investigation. (Registration No.: CTR20181665, http://www.chinadrugtrials. org."

Clinical • Journal • PK/PD data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Janagliflozin Treat Type 2 Diabetes Mellitus (T2DM) Inadequately Controlled With Metformin (clinicaltrials.gov) - P3; N=390; Recruiting; Sponsor: Sihuan Pharmaceutical Holdings Group Ltd.; Not yet recruiting ➔ Recruiting; Trial primary completion date: Dec 2020 ➔ Apr 2020

Clinical • Combination therapy • Enrollment open • Trial primary completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Janagliflozin Treat T2DM Monotherapy (clinicaltrials.gov) - P3; N=442; Recruiting; Sponsor: Sihuan Pharmaceutical Holdings Group Ltd.; Not yet recruiting ➔ Recruiting; Trial completion date: Dec 2021 ➔ Dec 2020

Clinical • Enrollment open • Monotherapy • Trial completion date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Translational Prediction of first-in-human Pharmacokinetics and Pharmacodynamics of janagliflozin, a selective SGLT2 inhibitor, using Allometric Scaling, Dedrick and PK/PD Modeling Methods. (PubMed, Eur J Pharm Sci) - "This study predicted human PK/PD characteristics of janagliflozin based on preclinical data and provide optimal dose design for janagliflozin FIH study based on pharmacologically effective level of same class drugs."

Journal • P1 data • PK/PD data

Pharmacokinetics, Pharmacodynamics, and Tolerability of Single- and Multiple-Dose of Janagliflozin, a Sodium-Glucose Cotransporter 2 Inhibitor, in Chinese Patients with Type 2 Diabetes Mellitus (ADA 2019) - "This study assessed the pharmacokinetics, pharmacodynamics, and tolerability of JGZ in Chinese patients with T2DM. In this double-blind, parallel-controlled study, 36 patients with inadequately controlled T2DM were randomized into JGZ 25 mg, JGZ 50 mg, dapagliflozin 10 mg, or placebo cohort in a 1:1:1:1 ratio. JGZ exhibited favorable pharmacokinetics profiles in Chinese patients with T2DM and was well tolerated. JGZ treatments resulted in increase in UGE and improvement in glycemic control. JGZ 25 mg and 50 mg are recommended for further clinical studies."

Clinical • Late-breaking abstract • PK/PD data

Accelerating Clinical Development of Janagliflozin, a Novel Antidiabetic Drug, Using Model-Informed Drug Development Strategy (ADA 2019) - "This MiDD strategy exhibited a good capability to accelerate early phase clinical development of JANA after confirmation from short-term clinical trials."

Clinical • Late-breaking abstract

Pharmacokinetics, Pharmacodynamics, and Tolerability of Single- and Multiple-Dose of Janagliflozin, a Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor, in Healthy Chinese Subjects (ADA 2019) - "In healthy Chinese subjects, JGZ was generally well tolerated and had favorable PK and PD profiles supporting a once-daily dosing regimen. The present studies suggest JGZ 25 and 50 mg could be the clinically recommended doses, which need to be further investigated in T2DM patients."

Clinical • Late-breaking abstract • PK/PD data