A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Crossover Study Evaluating the Safety, Tolerability and Pharmacokinetics of Various Doses of KP001 (Epinephrine Inhalation Aerosol) in Healthy Adult Volunteers While Assessing Carryover Effects

The goal of this clinical trial is to evaluate the safety, tolerability, and pharmacokinetics (PK) of several KP001 dose regimens to identify a treatment regimen with a PK profile that safely meets or exceeds the PK profile of existing injected epinephrine products. The main questions it aims to answer are:
* To evaluate any carryover effect with a 7-day washout of different dose regimens of KP001 in healthy adult volunteers.
* To evaluate the safety, tolerability and PK of different dose regimens of KP001 in healthy adult volunteers.
* To explore the safety, tolerability and PK of one KP001 dose regimen without inhalation (breath holding).
Participants will:
* Be admitted to clinical research unit (Day -1) and receive treatment the following day (Day 1) and then will be discharged
* Visit the clinic on Days 2 & 3 post dose for required assessments
* Visit the clinic 6 days post their last dose for dosing and repeated until 5 dosing visits have been completed
* Visit the clinic for a safety follow-up visit approximately 1 week from last dose administered

开始日期2025-05-09

申办/合作机构

Kokua Pharma Inc

NCT06821698

/ Recruiting临床1期

An Open-label Study to Determine the Effect of Oral Doses of KP-001 on Rosuvastatin and Caffeine PK After a Single Oral Administration and to Determine the Effect of Fluvoxamine on KP-001 PK After a Single Oral Administration in Volunteers

Part 1 will evaluate the effects of KP-001 as an inhibitor of BCRP on the PK of rosuvastatin. In the Treatment Period 1, a single dose of rosuvastatin will be administered. In the Treatment Period 2, KP-001 will be administered once daily for 7 days and a single dose of rosuvastatin will be administered. Blood PK assessments of rosuvastatin will be performed until 48 hours postdose in each Treatment Period. Part 2 will evaluate the effects of KP-001 as an inducer and inhibitor of CYP1A2 on the PK of caffeine. A single dose of caffeine will be administered in the Treatment Period 1. KP-001 will be administered once daily for 10 days and a single dose of caffeine will be administered in the Treatment Period 2. Blood PK assessments of caffeine will be performed until 24 hours postdose in each Treatment Period. Part 3 will evaluate the effects of fluvoxamine as an inhibitor of CYP1A2 on the PK of KP-001. A single dose of KP-001 will be administered in the Treatment Period 1. Fluvoxamine will be administered as a single dose on the first day and then twice daily for 5 days and a single dose of KP-001 will be administered in the Treatment Period 2. Blood PK assessments of KP-001 will be performed until 48 hours postdose in each Treatment Period.

开始日期2025-02-13

申办/合作机构

Kaken Pharmaceutical Co., Ltd.

NCT06619054

/ Not yet recruiting临床1期

An Open-label, Single-dose Study for the Evaluation of the Effect of Hepatic Impairment on the Pharmacokinetics and Safety of KP-001

This is a phase 1, open-label, non-randomized, parallel-group, single-dose study to assess the effect of hepatic impairment (assessed by the criteria of the Child-Pugh scale) on the pharmacokinetics (PK) and safety of KP-001 in adult male and non-childbearing potential female participants aged ≥20 years old.
The purpose of this study is to evaluate the effect of hepatic impairment on the PK and safety of KP-001. The study will also assess the effect of hepatic impairment on other PK parameters after single dose administration of KP-001.
The study will comprise 3 parts, and the study period for each part will consist of the following:
* Screening period: Up to 28 days before the administration of study intervention
* Treatment Period: Participants will be residential at the Clinical Unit from the day before the administration of the single dose of KP-001 (Day -1) until Day 3 (Discharge)
* Follow-up Visit: 7 days after discharge from the Clinical Unit (ie, Day 10) Participants will be enrolled into 4 cohorts according to the hepatic function status as summarized below. The study includes a control group of healthy participants with normal hepatic function.

开始日期2024-10-24

申办/合作机构

Kaken Pharmaceutical Co., Ltd.

100 项与 ART-001 相关的临床结果

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100 项与 ART-001 相关的转化医学

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100 项与 ART-001 相关的专利（医药）

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项与 ART-001 相关的文献（医药）

Orphanet Journal of Rare Diseases

A phase 2 randomized, double-blind trial of ART-001, a selective PI3Kα inhibitor, for the treatment of slow-flow vascular malformations

Article

作者: Hayashi, Ayato ; Ando, Haruhi ; Ohyama, Tetsuji ; Ochi, Junko ; Imagawa, Kotaro ; Nozaki, Taiki ; Nagabukuro, Hiroshi ; Nagao, Munetomo ; Tanaka, Akira ; Fujino, Akihiro ; Kiyosue, Hiro ; Kato, Aiko ; Ozeki, Michio ; Uemura, Naoto ; Shimizu, Fumiaki ; Horiuchi, Saya ; Kuniyeda, Kanako ; Suenobu, Souichi ; Nomura, Tadashi ; Aramaki-Hattori, Noriko

Abstract:

Background:

In patients with slow-flow vascular malformations (SFVMs) including venous malformations (VM), lymphatic malformations (LM) or Klippel–Trenaunay Syndrome (KTS), somatic gain-of-function mutations in genes encoding phosphatidyl inositol 3-kinase alpha (PI3Kα, gene name PIK3CA) have been identified. A phase 2 study was conducted with the patients to assess the efficacy and safety of ART-001 (serabelisib), an orally available selective PI3Kα inhibitor.

Methods:

This is a multicenter, randomized, double-blind, proof-of-concept, phase 2 trial. Eligible participants were patients aged 2 years and older, diagnosed either with VM, LM or KTS. Participants were administered either 50 or 100 mg of ART-001 for 24 weeks. The primary endpoint was the response rate defined as the proportion of participants who achieved ≥ 20% reduction in lesion volume at week 24. Secondary endpoints include safety, pharmacokinetics, pain, and quality of life scores.

Results:

Thirty-five patients (median age: 14 years old; VM, n = 17, KTS, n = 13 and LM, n = 5) were randomly assigned and received treatment (50 mg, n = 17 and 100 mg, n = 18). ART-001 showed a response rate: 29.4% (95% confidence interval 10.3–56.0%) at 50 mg and 33.3% (13.3–59.0%) at 100 mg. Mean lesion volume reductions at 50 mg and 100 mg were − 2.3% (95% CI − 14.3 to 9.6%) and − 12.6% (− 25.3 to 0.06%), respectively. No drug-related serious adverse events were observed. Treatment-emergent adverse events were generally mild to moderate and transient. Pharmacokinetic profiles were similar between pediatric and adolescent/adult patients except for lower Ctrough levels in pediatric patients.

Conclusion:

ART-001 was effective and well-tolerated in patients with SFVMs. These results support the further development of ART-001 in SFVMs and other PIK3CA-related overgrowth syndromes to confirm clinical benefits and long-term safety.Trial registration: Japan Registry of Clinical Trial, jRCT2071210027. Registered May 25 2021,https://jrct.niph.go.jp/en-latest-detail/jRCT2071210027

npj Vaccines

Neutralization of SARS-CoV-2 KP.1, KP.1.1, KP.2 and KP.3 by human and murine sera

Article

作者: Duan, Minrun ; Liu, Xueyuan ; Xu, Kun ; Dai, Lianpai ; Gao, George F. ; Gao, George F ; Yang, Ting ; Zhao, Xin ; Wang, Yuanzhuo ; Xie, Haitang ; Li, Dedong ; An, Yaling

We report SARS-CoV-2 KP.1, KP.1.1, KP.2 and KP.3 neutralizing antibody titers. They displayed increased immune evasion compared to JN.1, especially KP.1 and KP.3, for participants who experienced BF.7/BA.5.2 breakthrough infection or received bivalent (delta/BA.5) vaccine boosting. Second XBB sub-variants breakthrough infection enhanced the neutralization responses. HK.3-JN.1 RBD-heterodimer induced balanced and potent neutralizing responses against recently-circulating SARS-CoV-2 sub-variants in mice, supporting to replace the COVID-19 antigen containing JN.1 or its sub-variants.

100 项与 ART-001 相关的药物交易

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