The purpose of this study is to evaluate the effects of multiple therapeutic and supratherapeutic doses of KW-6356 on the QT interval corrected for heart rate in Japanese healthy adults.

开始日期2020-03-31

申办/合作机构

Kyowa Kirin Co., Ltd.

NCT04190654

/ Completed临床1期

A Pharmacokinetic Study of KW-6356 in Subjects With Mild and Moderate Hepatic Impairment Compared to Subjects With Normal Hepatic Function

This is an open-label, non-randomized, single-dose study to investigate the plasma PK of KW-6356 and its major metabolite, after a single oral dose of KW-6356, in subjects with mild or moderate hepatic impairment and in healthy adults

开始日期2019-11-26

申办/合作机构

Kyowa Kirin, Inc.

NCT04070495

/ Completed临床1期

A Drug Interaction Study of KW-6356 and Clarithromycin or Rifampicin (A Drug Interaction Study With a CYP3A4/5 Inhibitor or Inducer)

The purpose of this study is to investigate the effects of CYP3A4/5 inhibitor or inducer on the pharmacokinetics of KW-6356 when CYP3A4/5 inhibitor or inducer is orally administered to healthy Japanese men for 7 days.

开始日期2019-08-27

申办/合作机构

Kyowa Kirin Co., Ltd.

100 项与 KW-6356 相关的临床结果

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100 项与 KW-6356 相关的转化医学

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100 项与 KW-6356 相关的专利（医药）

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项与 KW-6356 相关的文献（医药）

2024-05-01·Clinical Pharmacology in Drug Development

Population Pharmacokinetics of the Novel Adenosine A_2A Antagonist/Inverse Agonist KW‐6356 and Its Active Metabolite Following Single and Multiple Oral Administration in Healthy Individuals and Patients with Parkinson's Disease

Article

作者: Ogawa, Kotoko ; Maeda, Hiroshi ; Tayama, Tomonori ; Marsteller, Douglas ; Kagawa, Yoshiyuki ; Hruska, Matthew W. ; Okada, Hiroki

AbstractKW‐6356 is a selective antagonist and inverse agonist of the adenosine A2A receptor. The primary aim of the present analysis was to characterize the pharmacokinetics (PK) of KW‐6356 and its active metabolite M6 in healthy subjects and patients with Parkinson's disease (PD). We pooled concentration‐time data from healthy subjects and patients with PD who were administered KW‐6356. Using these data, we developed a population PK model by sequentially fitting the KW‐6356 parameters followed by the M6 parameters. A first‐order absorption with a 1‐compartment model for KW‐6356 and a 1‐compartment model for M6 best described the profiles. The covariates included in the final models were food status (fed/fasted/unknown) on first‐order absorption rate constant, baseline serum albumin level on apparent clearance of KW‐6356, and baseline body weight on apparent volume of distribution of KW‐6356 and apparent clearance of M6. No covariate had a clinically meaningful impact on KW‐6356 or M6 exposure.

2023-12-01·Parkinsonism & Related Disorders

Randomized controlled trial of KW-6356 monotherapy in patients with early untreated Parkinson's disease

Article

作者: Kaneko, Satoshi ; Toru, Shuta ; Ishida, Yoshinori ; Ito, Kazunori ; Kawashima, Noriko ; Shimo, Yasushi ; Kitamura, Takeshi ; Takahashi, Ryosuke ; Tatsuoka, Yoshihisa ; Hiraiwa, Ren ; Negishi, Teruhiko ; Yoshinaga, Junji ; Yoshida, Kazuto ; Kanzato, Naomi ; Hattori, Tatsuya ; Mochizuki, Hideki ; Suzuki, Keisuke ; Ikebe, Shinichiro ; Kimura, Takashi ; Tsujino, Akira ; Kaneko, Chikako ; Orimo, Satoshi ; Fujimoto, Kenichi ; Saiki, Hidemoto ; Hasegawa, Kazuko ; Sugiyama, Kenichiro ; Abe, Takashi ; Maeda, Tetsuya ; Toda, Kazuo ; Naka, Takashi ; Yamada, Hitoshi ; Yamamoto, Mitsutoshi ; Deguchi, Kentaro ; Sakata, Mayumi ; Nomoto, Masahiro ; Isobe, Chiaki ; Hatsuta, Hiroyuki ; Sato, Akira ; Hattori, Nobutaka ; Tsuboi, Yoshio ; Morimoto, Nobutoshi ; Ishikawa, Mitsunori ; Kitayama, Michio ; Takeda, Atsushi ; Tomiyama, Masahiko ; Kosaka, Satoru ; Uozumi, Takenori ; Nishida, Yoshihiko ; Murata, Miho ; Tetsuya, Maeda ; Nishi, Masato ; Yamada, Kana ; Ito, Mizuki

INTRODUCTIONKW-6356 is a novel selective adenosine A_2A receptor antagonist/inverse agonist. We evaluated the efficacy and safety of KW-6356 as monotherapy in patients with early, untreated Parkinson's disease (PD).METHODSThis was a randomized, placebo-controlled, double-blind study conducted in Japan to investigate the efficacy and safety of once-daily KW-6356 (3 or 6 mg/day) orally administered as monotherapy for 12 weeks in patients with early PD (NCT02939391). The primary endpoint was the least squares means of change from baseline in the MDS-UPDRS Part III total score.RESULTSOverall, 168 patients were randomized and treated (KW-6356 3 mg/day n = 55; 6 mg/day n = 58, placebo n = 55); Week 12 completion rates were >90% per group. LS mean [95% CI] changes from baseline to Week 12 in MDS-UPDRS Part III total scores were -5.37 [-7.25, -3.48] for 3 mg/day, -4.76 [-6.55, -2.96] for 6 mg/day and -3.14 [-4.97, -1.30] for placebo. Changes from baseline were larger for both KW-6356 groups than for the placebo group at all time points. Secondary endpoints supported the primary findings with larger changes in MDS-UPDRS Part II, Parts II + III, and Total scores in the KW-6356 groups than in the placebo group. Treatment was well-tolerated; the most common treatment-emergent adverse events with KW-6356 were constipation (n = 4 [7.3%] and n = 6 [10.3%] in the 3 and 6 mg/day groups, respectively) followed by nasopharyngitis (n = 4 [7.3%] and n = 5 [8.6%] in the 3 and 6 mg/day groups, respectively).CONCLUSIONKW-6356 monotherapy is well tolerated and more effective than placebo in patients with early, untreated PD.

2023-08-01·Clinical Pharmacology in Drug Development

Safety, Tolerability, and Pharmacokinetics of the Novel Adenosine A_2A Antagonist/Inverse Agonist KW‐6356 Following Single and Multiple Oral Administration in Healthy Volunteers

Article

作者: Kagawa, Yoshiyuki ; Maeda, Hiroshi ; Ishiuchi, Masatake ; Oka, Yuichi ; Tayama, Tomonori ; Hruska, Matthew ; Sugiyama, Kenichiro ; Nagata, Yoshinori

AbstractKW‐6356 is an adenosine A2A receptor–selective antagonist and inverse agonist. We conducted 2 studies: study 6356‐001 (no NCT number), a randomized, double‐blind, placebo‐controlled phase 1 trial of single ascending (1, 3, 10 mg) and multiple (6 mg once daily) oral doses of KW‐6356 in healthy Japanese subjects; and study 6356‐004 (NCT03830528), including a randomized, double‐blind, placebo‐controlled phase 1 trial of single ascending (21, 42, 60 mg) and multiple (24 mg once daily) oral doses of KW‐6356, and a phase 1 open‐label trial of multiple oral doses (6 mg once daily) of KW‐6356 in healthy Japanese and White subjects, to evaluate the safety, tolerability, and pharmacokinetics of KW‐6356. KW‐6356 was well tolerated after administration of single doses of up to 60 mg and multiple doses of up to 24 mg once daily for 14 days. The pharmacokinetics of KW‐6356 were linear after a single dose of up to 60 mg KW‐6356. The mean terminal elimination half‐life of KW‐6356 ranged from 18.4 to 43.1 hours following administration of single doses of 1–60 mg. There was no clear difference in the safety or pharmacokinetics of KW‐6356 between healthy Japanese and White subjects.

项与 KW-6356 相关的新闻（医药）

2023-10-05

·FierceBiotech

Orchard lands $387M Kyowa buyout, reaping harvest of US gene therapy progress

Kyowa Kirin has agreed to pay an initial $16 a share for Orchard Therapeutics. Kyowa Kirin has addressed calls to strengthen its late-phase pipeline by inking a deal to buy Orchard Therapeutics for $387.4 million upfront. The takeover will give Kyowa control of a gene therapy that is on track to win approval in the U.S. in March. Orchard, like many gene therapy stocks, has had a torrid time on public markets, seeing its share price plummet more than 95% since its IPO in 2018. The biotech has reclaimed a small slice of the lost ground in recent weeks with the news that the FDA has accepted an approval application for review, sending its stock up, and has now been rewarded with an acquisition at a valuation it last commanded in 2021. The takeover will give Kyowa ownership of OTL-200, an early-onset metachromatic leukodystrophy gene therapy that is under review at the FDA. The therapy is already sold in Europe as Libmeldy and generated $6.6 million in the second quarter. Kyowa thinks it can maximize the value of Libmeldy while accelerating development of a pipeline that features gene therapies against rare diseases, namely mucopolysaccharidosis type I and type IIIA, as well as more common conditions including frontotemporal dementia and a form of Crohn’s disease. The assets will bolster a pipeline that has taken big hits over the past 18 months. When Kyowa sketched out its strategy in 2021, it built (PDF) its vision for the second half of the decade around three next-generation candidates. Kyowa stopped work on one of the candidates, the Parkinson’s prospect KW-6356, in July 2022 (PDF). Months later, the drugmaker and its partner MEI Pharma pulled the plug on development of another of the assets, cancer therapy zandelisib, outside of Japan. The discontinuations left a hole in Kyowa’s strategy, but it kept its midterm targets, leading an analyst on an August conference call to question (PDF) whether the biotech planned to plug the gap by acquiring late-stage assets. In response, Kyowa CEO Masashi Miyamoto, Ph.D., said the company had “a considerable amount of cash” and was working “proactively to acquire external assets.” Kyowa has agreed to pay an initial $16 per share for Orchard. Investors in the gene therapy specialist stand to pocket an additional $1 a share if the FDA approves the candidate that is now under review. The FDA is set to make a decision by March 18, with approval expected to add $90.2 million to the value of the deal. Even at $16 a share, the acquisition represents a big premium. Orchard has traded around $5 for most of the year, although the recent surge raised the share price to $8. Investors sent the stock up to $16 after news of the Kyowa buyout broke.

并购IPO基因疗法

100 项与 KW-6356 相关的药物交易

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