KW-6356 / Kyowa Kirin - LARVOL DELTA

Population Pharmacokinetics of the Novel Adenosine A Antagonist/Inverse Agonist KW-6356 and Its Active Metabolite Following Single and Multiple Oral Administration in Healthy Individuals and Patients with Parkinson's Disease. (PubMed, Clin Pharmacol Drug Dev) - "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."

Journal • PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease

Randomized controlled trial of KW-6356 monotherapy in patients with early untreated Parkinson's disease. (PubMed, Parkinsonism Relat Disord) - P2 | "KW-6356 monotherapy is well tolerated and more effective than placebo in patients with early, untreated PD."

Journal • Monotherapy • CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Movement Disorders • Parkinson's Disease

The adenosine A receptor antagonist/inverse agonist, KW-6356 enhances the anti-parkinsonian activity of L-DOPA with a low risk of dyskinesia in MPTP-treated common marmosets. (PubMed, J Pharmacol Sci) - "Chronic co-administration of KW-6356 (1 mg/kg) with a low dose of L-DOPA (2.5 mg/kg) for 21 days increased the degree of dyskinesia induced by the low dose of L-DOPA, but the amplitude of dyskinesia induced by combined administration of KW-6356 (1 mg/kg) with L-DOPA (2.5 mg/kg) was lower than that induced by an optimal dose of L-DOPA (10 mg/kg). These results suggest that KW-6356 can be used to potentiate the effects of a wide range of L-DOPA doses with a low risk of dyskinesia for the treatment of PD."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Anti-parkinsonian activity of the adenosine A receptor antagonist/inverse agonist KW-6356 as monotherapy in MPTP-treated common marmosets. (PubMed, Eur J Pharmacol) - "However, the first-generation A antagonist istradefylline, which is approved for use as an adjunct treatment to L-DOPA/decarboxylase inhibitor in adult PD patients experiencing OFF episodes, has not shown statistically significant efficacy as monotherapy. Repeated administration of KW-6356 induced little dyskinesia in MPTP-treated common marmosets primed to exhibit dyskinesia by prior exposure to L-DOPA. These results indicate that KW-6356 can be a novel non-dopaminergic therapy as monotherapy without inducing dyskinesia in PD patients."

Journal • Monotherapy • CNS Disorders • Movement Disorders • Parkinson's Disease

In vitro pharmacological profile of KW-6356, a novel adenosine A receptor antagonist/inverse agonist. (PubMed, Mol Pharmacol) - "Significance Statement KW-6356 is a potent and selective adenosine A receptor antagonist/inverse agonist and exhibits insurmountable antagonism, while istradefylline, a first-generation adenosine A receptor antagonist, exhibits surmountable antagonism. Structural studies of adenosine A receptor in complex with KW-6356 and istradefylline explain the characteristic differences in the pharmacological properties of KW-6356 and istradefylline."

Journal • Preclinical • CNS Disorders • Movement Disorders • Parkinson's Disease

Safety, Tolerability, and Pharmacokinetics of the Novel Adenosine A Antagonist/Inverse Agonist KW-6356 Following Single and Multiple Oral Administration in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - P1 | "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."

Clinical • Journal • PK/PD data • CNS Disorders • Movement Disorders • Parkinson's Disease

Effect of KW-6356, a novel adenosine A2A receptor antagonist/inverse agonist, on motor and non-motor symptoms in Parkinson’s disease patients as an adjunct to levodopa therapy: Results of Phase 2b study (MDS Congress 2022) - P2, P2b | "This study demonstrates that KW-6356 has a favorable efficacy and acceptable safety profile as an adjunct to levodopa in PD patients and justifies further development as a new antiparkinsonian treatment. Post-hoc analyses suggest KW-6356 6 mg could provide potential benefits for PD patients with sleep problems."

Clinical • P2b data • CNS Disorders • Parkinson's Disease • Sleep Disorder • ADORA2A

"@VertexPharma Acquires @ViaCyte for USD 320 Million. @KyowaKirin_US Drops Nourianz follow-up KW-6356 for Parkinson’s. @grunenthalgroup Acquires @Bayer Testosterone Drug Rights for €500 Million. (2/3)" (@delve_insight)

CNS Disorders • Movement Disorders • Parkinson's Disease

Kyowa Kirin drops Nourianz follow-up KW-6356 for Parkinson’s (pharmaphorum) - "Despite reporting proof-of-concept results in a mid-stage trial, Kyowa Kirin has decided to discontinue development of its Parkinson’s disease candidate KW-6356, a drug in the adenosine A2A receptor antagonist class. The Japanese drugmaker said...the decision wasn’t taken for clinical reasons, as trials suggested the drug had potential as a monotherapy and in combination with levodopa in relieving both motor and non-motor symptoms of Parkinson’s. Rather, it decided to drop the programme after 'a thorough evaluation of the global regulatory landscape, development hurdles, and timelines for potential market entry.'"

Discontinued • CNS Disorders • Parkinson's Disease

Kyowa Kirin Announces Positive Phase 2b Results for KW-6356 in Patients with Parkinson's Disease (Kyowa Hakko Kirin Pharma Press Release) - P2b, N=502; NCT03703570; Sponsor: Kyowa Kirin Co., Ltd.; "Kyowa Kirin Co., Ltd....announces today that the phase 2b study of KW-6356 in patients with Parkinson's disease on treatment with levodopa-containing preparations has met the primary endpoint....The study result met its primary endpoint as the change in the KW-6356 group was greater than in the placebo group with a statistically significant difference. No major safety issues were observed in any of the groups."

P2b data • CNS Disorders • Parkinson's Disease

A Through QT/QTc Study of KW-6356 (clinicaltrials.gov) - P1; N=128; Completed; Sponsor: Kyowa Kirin Co., Ltd.; Recruiting ➔ Completed

Clinical • Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

A Study of KW-6356 in Patients With Parkinson's Disease on Treatment With Levodopa-containing Preparations (clinicaltrials.gov) - P2b; N=502; Completed; Sponsor: Kyowa Kirin Co., Ltd.; Active, not recruiting ➔ Completed

Clinical • Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

Single-dose Study to Investigate the Plasma PK of KW-6356 and Its Major Metabolite (clinicaltrials.gov) - P1; N=26; Completed; Sponsor: Kyowa Kirin Pharmaceutical Development, Inc.; Recruiting ➔ Completed

Clinical • Trial completion

A Through QT/QTc Study of KW-6356 (clinicaltrials.gov) - P1; N=128; Recruiting; Sponsor: Kyowa Kirin Co., Ltd.

Clinical • New P1 trial

Single-dose Study to Investigate the Plasma PK of KW-6356 and Its Major Metabolite (clinicaltrials.gov) - P1; N=32; Recruiting; Sponsor: Kyowa Kirin Pharmaceutical Development, Inc.

Clinical • New P1 trial

A Drug Interaction Study of KW-6356 and Clarithromycin or Rifampicin (clinicaltrials.gov) - P1; N=20; Completed; Sponsor: Kyowa Kirin Co., Ltd.; Recruiting ➔ Completed

Trial completion

A Drug Interaction Study of KW-6356 With Midazolam, Caffeine, or Rosuvastatin (clinicaltrials.gov) - P1; N=50; Completed; Sponsor: Kyowa Kirin Co., Ltd.; Active, not recruiting ➔ Completed

Trial completion

A Study of Single and Multiple Doses of KW-6356 in Healthy Subjects (clinicaltrials.gov) - P1; N=48; Completed; Sponsor: Kyowa Kirin Co., Ltd.; Recruiting ➔ Completed

Clinical • Trial completion

A Study of KW-6356 in Patients With Parkinson's Disease on Treatment With Levodopa-containing Preparations (clinicaltrials.gov) - P2b; N=502; Active, not recruiting; Sponsor: Kyowa Kirin Co., Ltd.; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed

Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of [14C]-KW-6356 (clinicaltrials.gov) - P1; N=8; Completed; Sponsor: Kyowa Kirin Pharmaceutical Development, Inc.

Clinical • New P1 trial

A Drug Interaction Study of KW-6356 and Clarithromycin or Rifampicin (clinicaltrials.gov) - P1; N=20; Recruiting; Sponsor: Kyowa Kirin Co., Ltd.; Not yet recruiting ➔ Recruiting

Enrollment open

A Drug Interaction Study of KW-6356 and Clarithromycin or Rifampicin (clinicaltrials.gov) - P1; N=20; Not yet recruiting; Sponsor: Kyowa Kirin Co., Ltd.

New P1 trial

A Drug Interaction Study of KW-6356 With Midazolam, Caffeine, or Rosuvastatin (clinicaltrials.gov) - P1; N=50; Active, not recruiting; Sponsor: Kyowa Kirin Co., Ltd.; Recruiting ➔ Active, not recruiting

Enrollment closed

A Drug Interaction Study of KW-6356 With Midazolam, Caffeine, or Rosuvastatin (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Kyowa Hakko Kirin Co., Ltd; Not yet recruiting ➔ Recruiting

Enrollment open

A Drug Interaction Study of KW-6356 With Midazolam, Caffeine, or Rosuvastatin (clinicaltrials.gov) - P1; N=50; Not yet recruiting; Sponsor: Kyowa Hakko Kirin Co., Ltd

New P1 trial