An investigator initiated clinical trial in healthy adults to evaluate safety and pharmacokinetics of WN1316, a candidate drug of amyotrophic lateral sclerosis - An investigator initiated clinical trial in healthy adults of WN1316

Start Date21 Sep 2014

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Clinical Research Hospital Tokyo

100 Clinical Results associated with Clinical Research Hospital Tokyo

0 Patents (Medical) associated with Clinical Research Hospital Tokyo

Literatures (Medical) associated with Clinical Research Hospital Tokyo

01 Sep 2020·Drug Research

Effects of Child-Pugh B Cirrhosis on Pharmacokinetics of Tofogliflozin, a New Sodium-Glucose Co-Transporter (SGLT2) Inhibitor

Article

Author: Ikegami, Fumiaki ; Ohba, Yasuhiro ; Nakamura, Koichi ; Saito, Tomohisa ; Abe, Kazumichi ; Shimada, Sumire ; Miyata, Kumiko ; Ohnishi, Akihiro ; Yamada, Haruki ; Takahashi, Atsushi ; Terao, Kimio ; Inano, Akihiro ; Ohira, Hiromasa

Abstract Background Tofogliflozin is a highly selective sodium-glucose co-transporter 2 (SGLT2) inhibitor. A mass balance study with combinations of microdoses revealed that tofogliflozin has high oral bioavailability (97.5%) and that tofogliflozin in circulation is eliminated primarily by metabolic pathways, with the liver playing a prominent role in elimination. Objectives This study aimed to evaluate the effect of moderate hepatic impairment on the pharmacokinetics of tofogliflozin and on the pharmacodynamics (urinary glucose excretion [UGE]). Methods In an open-label, parallel-group study, 17 subjects (9 with moderate hepatic impairment [Child-Pugh Class B, score 7–9] and 8 healthy) received a single oral dose of 40 mg tofogliflozin. Plasma and urine concentrations of tofogliflozin were determined. Accumulated UGE, adverse events, and physiological and laboratory test data were monitored. Results Geometric mean ratio (GMR; geometric mean value for subjects with moderate hepatic impairment / geometric mean value for healthy subjects) of Cmax was 1.47 and GMR of AUCinf was 1.70. Moderate hepatic impairment had only a little effect on tmax and CLR but it prolonged MRT. The levels of cumulative UGE were similar between the 2 groups. No clinically significant adverse events, laboratory test values, or physiological test values were observed in any subject. Conclusions Moderate hepatic impairment increased Cmax and AUCinf of tofogliflozin by 47% and 70%, respectively. This increase in tofogliflozin exposure did not increase UGE in hepatically impaired subjects. A single oral dose of 40 mg tofogliflozin was well tolerated, supporting dose adjustment is unnecessary even in moderately hepatically impaired subjects.

01 Mar 2020·Clinical and Experimental NephrologyQ3 · MEDICINE

Effects of mild and moderate renal dysfunction on pharmacokinetics, pharmacodynamics, and safety of dotinurad: a novel selective urate reabsorption inhibitor

Q3 · MEDICINE

Article

Author: Fushimi, Masahiko ; Sasaki, Tomomitsu ; Hosoya, Tatsuo ; Ohashi, Tetsuo ; Fukase, Hiroyuki ; Okui, Daisuke

AbstractBackgroundDotinurad, a novel selective urate reabsorption inhibitor, exerts a serum uric acid-lowering effect by selectively inhibiting urate transporter 1 (URAT1) in patients with hyperuricemia. It is generally known that the progression of renal dysfunction is associated with a reduction in the serum uric acid-lowering effects of uricosuric drugs. We, therefore, investigated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of dotinurad in subjects with renal dysfunction.MethodsThis was a parallel-group, open-label, single-dose clinical pharmacology study. Dotinurad (1 mg) was administered once, orally to subjects with mild (estimated glomerular filtration rate [eGFR], ≥ 60 to < 90 mL/min/1.73 m2) or moderate (eGFR, ≥ 30 to < 60 mL/min/1.73 m2) renal dysfunction or normal (eGFR, ≥ 90 mL/min/1.73 m2) renal function.ResultsThe time-course of mean plasma concentration of dotinurad had similar profiles across the groups. Regarding PK, there was no significant difference between the renal dysfunction groups and normal renal function group. Regarding PD, the maximum reduction rate in serum uric acid levels and the fractional uric acid excretion (FE) ratio (FE0–24/FE−24–0) were significantly lower in the moderate renal dysfunction group than in the normal renal function group. However, other PD parameters were not significantly different among the groups. No notable adverse events or adverse drug reactions were observed in this study.ConclusionThese results suggested that no dose adjustment might be necessary when administering dotinurad to patients with mild-to-moderate renal dysfunction.ClinicalTrials.gov Identifier: NCT02347046.

01 Mar 2020·Clinical Drug InvestigationQ4 · MEDICINE

Food Effect on a Single High Dose of Carotegrast Methyl, an Oral Antagonist of α4-Integrin, in Healthy Male Subjects: A Randomised, Placebo-Controlled, Double-Blind Study

Q4 · MEDICINE

Article

Author: Fukase, Hiroyuki ; Furuie, Hidetoshi ; Oikawa, Ichiro ; Ikeda, Naoki ; Kajioka, Toshifumi

BACKGROUND AND OBJECTIVESCarotegrast methyl, a novel prodrug, oral antagonist of α4-integrin, is in development for the treatment of active ulcerative colitis. This randomised, placebo-controlled, double-blind, crossover study evaluated the effect of food on the pharmacokinetics and pharmacodynamics as well as the safety profile after a single dose of carotegrast methyl in healthy male subjects.METHODSSubjects were randomised to receive a single dose of carotegrast methyl (240, 480 or 960 mg) or placebo in a 6:2 ratio and received the study drug under both fed and fasted conditions separated by an 8-day washout. The pharmacokinetic profiles of carotegrast methyl and its active metabolite, carotegrast, were assessed. The pharmacodynamic profile was evaluated according to a change in the peripheral lymphocyte count. Safety was monitored throughout.RESULTSBased on the area under the time curve from zero to the time of the last quantifiable concentration (AUC_last), food reduced systemic exposure to both carotegrast methyl and carotegrast by 21-57% and 5-29%, respectively. The fed-to-fasted ratio of least square means for the increase in the lymphocyte count was almost at unity in each dose, indicating no food effect on pharmacodynamics. The time ≥ 90% of maximum effect was prolonged dose dependently, suggesting that a 960 mg-dose can provide a long-lasting effect. Reported adverse events were all mild.CONCLUSIONSDespite the reduced systemic exposure to both carotegrast methyl and carotegrast, food had no effect on the increase in lymphocyte count. A single administration of carotegrast methyl up to 960 mg was found to be safe.

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100 Translational Medicine associated with Clinical Research Hospital Tokyo

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