A Phase I, Double Blind, Randomized, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Orally Administered 'Ivaltinostat' Capsule in Healthy Male Volunteers

A Phase I, Double blind, Randomized, Placebo-controlled, Multiple Ascending Dose Study to evaluate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Orally Administered 'CG-745' Capsule in Healthy Male Volunteers

开始日期2023-03-09

申办/合作机构

Machaon Biotherapeutics

NCT05249101 / Recruiting临床1/2期

A Phase 1b/2, Dose-escalation, Randomized, Multicenter Study of Maintenance Ivaltinostat Plus Capecitabine or Capecitabine in Patients With Metastatic Pancreatic Adenocarcinoma Whose Disease Has Not Progressed on FOLFIRINOX

This study is a Phase 1b/2, dose-escalation, randomized, multicenter study to assess the efficacy, safety, tolerability, and PK of ivaltinostat in combination with capecitabine and capecitabine monotherapy in patients with metastatic pancreatic adenocarcinoma whose disease has not progressed on a first line fluoropyrimidine-based chemotherapy (e.g., FOLFIRINOX).
In Phase 1b, 3 dose levels of ivaltinostat will be studied in combination with a fixed dose of capecitabine to determine the RP2D of ivaltinostat.
In Phase 2, patients will be randomized in a 1:1 ratio to the combination of ivaltinostat and capecitabine or to capecitabine monotherapy. A fixed dose for capecitabine 1000 mg/m2 orally twice daily will be taken on Days 1 to 14, and the RP2D of ivaltinostat will be administered intravenously once a week for 2 weeks, followed by 1 week of rest. One cycle consists of 21 days. Tumor response during study treatment will be assessed every 6 weeks up to Cycle 10, then every 9 weeks afterwards using RECIST v1.1 criteria.

开始日期2022-08-15

申办/合作机构

CG Pharmaceuticals, Inc.

NCT05345912 / Completed临床1期

A Randomized, Double Blind, Placebo-controlled, Dose-escalation, Crossover Study to Compare and Evaluate the Pharmacokinetics and Safety of 'CG-745 IV' Intravenous Formulation and 'CG-750' Capsule Formulation in Healthy Male Adults

A randomized, placebo-controlled, dose-escalation, crossover study.

开始日期2019-12-16

申办/合作机构

CG Invites Co., Ltd.

100 项与 Ivaltinostat 相关的临床结果

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100 项与 Ivaltinostat 相关的转化医学

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100 项与 Ivaltinostat 相关的专利（医药）

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项与 Ivaltinostat 相关的文献（医药）

2024-04-01·British Journal of Clinical Pharmacology

Pharmacokinetics, pharmacodynamics and safety of oral formulation (CG‐750) of ivaltinostat, a histone deacetylase inhibitor, compared to IV formulation (CG‐745)

Article

作者: Huh, Ki Young ; Lee, SeungHwan ; Kim, Byungwook ; Yu, Kyung-Sang

AimsCG‐750 is an oral formulation of ivaltinostat, a newly developing histone deacetylase (HDAC) inhibitor. This study aimed to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of an oral formulation (CG‐750) of ivaltinostat compared to an intravenous (IV) formulation (CG‐745).MethodsA randomized, double‐blind, placebo‐controlled study was conducted in three cohorts. Subjects received either CG‐745 (Cohorts 1 and 3: 125 mg; Cohort 2: 250 mg) or placebo followed by CG‐750 (Cohort 1: 125 mg; Cohort 2: 375 mg; Cohort 3: 750 mg) or placebo. Blood samples for PK and PD assessment were collected up to 72 h post‐dose. Histone H3 acetylation at sites K9, K9/K14 and K27 was assessed for area under the % acetylation induction versus time curve (AUEC).ResultsA total of 25 subjects were randomized, and 23 subjects completed the study (Cohort 1, n = 6; Cohort 2, n = 6; Cohort 3, n = 6; placebo, n = 5). The mean bioavailability of CG‐750 was 10.6% (range: 4.18%–21.33%) and displayed linear PK in the dose range of 125–750 mg. The comparison of AUEC between formulations and the evaluation of the dose–AUEC relationship were inconclusive, due to the small sample sizes and significant variability observed in PD markers. All adverse events (AEs) were transient and of mild or moderate intensity.ConclusionsThe oral formulation of ivaltinostat (CG‐750) was generally well tolerated after a single dose. CG‐750 displayed a mean bioavailability of 10.6%.

2022-11-01·International Journal of Cancer

A phase I/II study of ivaltinostat combined with gemcitabine and erlotinib in patients with untreated locally advanced or metastatic pancreatic adenocarcinoma

Article

作者: Cho, Sangsook ; Park, Seung Woo ; Jo, Jung Hyun ; Jung, Dawoon E. ; Lee, Hee Seung ; Park, Soo Been ; Chung, Moon Jae ; Bang, Seungmin ; Song, Si Young ; Park, Jeong Youp

AbstractThis phase I/II study evaluated the safety and efficacy of a new histone deacetylase (HDAC) inhibitor, ivaltinostat, in combination with gemcitabine and erlotinib for advanced pancreatic ductal adenocarcinoma (PDAC). Patients diagnosed with unresectable, histologically confirmed PDAC who had not undergone previous therapy were eligible. Phase I had a 3 + 3 dose escalation design to determine the maximum tolerable dose (MTD) of ivaltinostat (intravenously on days 1, 8 and 15) with gemcitabine (1000 mg/m2 intravenously on days 1, 8 and 15) and erlotinib (100 mg/day, orally) for a 28‐day cycle. In phase II, patients received a six‐cycle treatment with the MTD of ivaltinostat determined in phase I. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), disease control rate (DCR) and progression‐free survival (PFS). The MTD of ivaltinostat for the phase II trial was determined to be 250 mg/m2. In phase II, 24 patients were enrolled. The median OS and PFS were 8.6 (95% confidence interval [CI]: 5.3‐11.2) and 5.3 months (95% CI: 3.7‐5.8). Of the 16 patients evaluated for response, ORR and DCR were 25.0% and 93.8% with a median OS/PFS of 10.8 (95% CI: 8.3‐16.7)/5.8 (95% CI: 4.6‐6.7) months. Correlative studies showed that mutation burden detected by cfDNA and specific blood markers such as TIMP1, pro‐MMP10, PECAM1, proMMP‐2 and IGFBP1 were associated with clinical outcomes. Although the result of a small study, a combination of ivaltinostat, gemcitabine and erlotinib appeared to be a potential treatment option for advanced PDAC.

2021-10-01·Hypertension1区 · 医学

Inhibition of HDACs (Histone Deacetylases) Ameliorates High-Fat Diet–Induced Hypertension Through Restoration of the MsrA (Methionine Sulfoxide Reductase A)/Hydrogen Sulfide Axis

1区 · 医学

Article

作者: Kim, InKyeom ; Jang, GiBong ; Jung, Jin Ki ; Park, Kwon Moo ; Kim, Jee In ; Yoon, Ga-Eun

Hydrogen sulfide (H 2 S) is an endogenous gaseous antioxidant and antihypertensive molecule produced during the homocysteine metabolism. MsrA (methionine sulfoxide reductase A) enables the metabolism of homocysteine by reducing methionine sulfoxide to methionine. Although HDAC (histone deacetylase) inhibition has been reported to show blood pressure lowering effects, their effects on endogenous H 2 S production are largely unknown. Here, we assessed the relevance of MsrA in high-fat diet (HFD)-induced hypertension and the effect of HDAC inhibition on MsrA expression, H 2 S production, and hypertension. Male C57BL/6 mice were fed a normal diet or HFD. HFD increased blood pressure and activities of HDAC3 and 6 but downregulated MsrA in the mesenteric arteries and the serum H 2 S level. HFD upregulated 4 hydroxynonenal, TNF (tumor necrosis factor)-α, and IL (interleukin)-6, and vasocontractile proteins. The histone H3 acetylation of the MsrA promoter was decreased by HFD. In hypertensive HFD-fed mice, administration of the HDAC inhibitor CG200745 lowered blood pressure and increased serum H 2 S level. CG200745 increased acetylation of histone H3 and MsrA levels in the mesenteric arteries while downregulating oxidative stress, inflammation, and vasocontractile proteins. Silencing of MsrA in the vascular smooth muscle cells recapitulated HFD-induced in vivo hypertensive effects. CG200745 increased the histone H3 acetylation of the MsrA promoter, MsrA expression, and H 2 S production in vascular smooth muscle cells, supporting the in vivo results. Collectively, HFD-induced downregulation of MsrA plays a pivotal role in HFD-induced hypertension by reducing H 2 S levels. MsrA expression is epigenetically regulated by HDAC inhibitors, providing HDAC inhibitors as a therapeutic option and MsrA and H 2 S as novel therapeutic targets. Graphic Abstract: An online graphic abstract is available for this article.

项与 Ivaltinostat 相关的新闻（医药）

2024-05-29

·PRNewswire

CG Pharmaceuticals Prepares to Showcase Its Ongoing Phase 2 Study for Ivaltinostat in Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

ORINDA, Calif., May 29, 2024 /PRNewswire/ -- CG Pharmaceuticals, a company dedicated to advancing innovative therapies to improve the lives of patients with cancer, prepares to showcase its advancements in metastatic PDAC therapy. The study design of a randomized multi-center Phase 2 US clinical trial, which is actively enrolling patients, is scheduled to be presented on June 1st, 1:30 – 4:30 PM CDT at the ASCO Annual Meeting (ClinicalTrials.gov NCT05249101). "Metastatic PDAC continues to be an aggressive cancer with limited treatment options. We are pleased that CG Pharmaceuticals is investing in pancreatic cancer research and look forward to the results of their trial," said Anna Berkenblit, MD, MMSc, Chief Scientific and Medical Officer at the Pancreatic Cancer Action Network (PanCAN). "Clinical trials are an important aspect of accelerating new developments that improve outcomes for pancreatic cancer patients. PanCAN recommends that patients with PDAC consider participating in clinical trials." In the Phase 1b study, 28 patients with locally advanced or metastatic PDAC who had received at least one prior line of therapy were administered ivaltinostat at three dose levels (60, 125, and 250 mg/m²) in combination with capecitabine. The study demonstrated a favorable safety profile, with no treatment-related serious adverse events. At the time of data cutoff (5/6/2024), 16 patients were alive with 3 patients continuing treatment, and 7 patients were treated for longer than 6 months with the longest duration of treatment of 16 months. The Phase 2 study compares the efficacy of ivaltinostat/capecitabine combination therapy versus capecitabine monotherapy in metastatic PDAC patients who have shown no evidence of disease progression after first-line chemotherapy. Efficacy endpoints include progression-free survival, objective response rate, disease control rate, and overall survival. About Ivaltinostat: Ivaltinostat is a potential first-in-class novel therapeutic candidate for PDAC that inhibits enzymatic activity of histone deacetylase and has been evaluated for solid tumors and hematologic malignancies. CG Pharmaceuticals continues to make strides in its mission to provide innovative treatment options for metastatic PDAC patients. Forward-Looking Statement Disclosure: This press release may contain certain forward-looking statements relating to the goals, business strategy, financial and market position, product development, and projections for the Company. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them. No forward-looking statements can be guaranteed, and actual results may differ. CG Pharmaceuticals undertakes no obligation to update any forward-looking statements contained in this release, except as required by law. CG Pharmaceuticals Contact: Douglas An Head of Finance and IR Representative [email protected] SOURCE CG Pharmaceuticals, Inc.

临床2期临床1期临床结果

2024-05-06

·PRNewswire

CG Pharmaceuticals, Inc. to Present at the 2024 ASCO Annual Meeting in Chicago on June 1st

ORINDA, Calif., May 6, 2024 /PRNewswire/ -- CG Pharmaceuticals, a late-stage clinical biopharmaceutical company specializing in metastatic pancreatic ductal adenocarcinoma (PDAC) maintenance therapy (NCT05249101), will feature one of our investigators, Dr. Christos Fountzilas from Roswell Park Comprehensive Cancer Center, at the ASCO Annual Meeting in Chicago on June 1st, 1:30 – 4:30 PM CDT, during the Gastrointestinal Cancer session (TPS4206). He will be presenting some of the findings from our completed Phase 1b and study design of the on-going Phase 2 clinical trial. Commencement of treatment for the first patient of Phase 2 began on January 9th, 2024, and the study will continue to recruit patients in approximately 25 institutions throughout the US. Continue Reading In the Phase 2 study, metastatic PDAC patients who show no evidence of disease progression after treatment with FOLFIRINOX, mFOLFIRINOX or NALIRIFOX will receive either the ivaltinostat/capecitabine combination therapy or capecitabine monotherapy after randomization. The primary endpoint is to evaluate ivaltinostat's effect on improving progression free survival (PFS), while key secondary endpoints include objective response rate (ORR), disease control rate (DCR), and overall survival (OS). CG Pharmaceuticals, Inc. to Present at the 2024 ASCO Annual Meeting in Chicago on June 1st Post this About Ivaltinostat: Ivaltinostat is a potential first-in-class novel therapeutic candidate for pancreatic ductal adenocarcinoma that inhibits enzymatic activity of histone deacetylase and has been evaluated for solid tumors and hematologic malignancies. About CG Pharmaceuticals: CG Pharmaceuticals is a late-stage clinical biopharmaceutical company that is dedicated to advancing innovative therapies to improve the lives of patients with cancer. CG Pharmaceuticals is located in the San Francisco Bay Area. Forward-Looking Statement Disclosure: This press release may contain certain forward-looking statements relating to the goals, business strategy, financial and market position, product development, and projections for the Company. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statements can be guaranteed, and actual results may differ. The information in this release is provided only as of the written date, and CG Pharmaceuticals undertakes no obligation to update any forward-looking statements contained in this release, except as required by law. CG Pharmaceuticals Contact: Douglas An Head of Finance and IR Representative [email protected] SOURCE CG Pharmaceuticals, Inc.

临床2期

2023-11-18

·PRNewswire

CG Pharmaceuticals Announces the Commencement of Phase 2 Study for Metastatic Pancreatic Cancer

ORINDA, Calif., Nov. 17, 2023 /PRNewswire/ -- CG Pharmaceuticals announces the commencement of Phase 2 study for metastatic pancreatic ductal adenocarcinoma (PDAC) with the recommended Phase 2 dose (RP2D) of ivaltinostat (ClinicalTrials.gov ID NCT05249101). Continue Reading The RP2D of ivaltinostat (250 mg/m2) was determined by the Safety Review Committee (SRC) following a thorough safety data review from 3 cohorts of increasing dose levels of ivaltinostat in combination with a fixed dose of capecitabine. The SRC has unanimously recommended proceeding to Phase 2, marking a significant milestone, effective immediately, the study is open for the enrollment of patients. CG Pharmaceuticals Announces Commencement of the Phase 2 Metastatic Pancreatic Ductal Adenocarcinoma Study Post this In Phase 2, metastatic PDAC patients who show no evidence of disease progression after an initial treatment with FOLFIRINOX will receive either combination therapy or capecitabine monotherapy. The primary endpoint is progression free survival. Dr. Gene Cho, Vice President of Global Strategic Planning at CG Pharmaceuticals, expressed his excitement, "I am thrilled and honored to share this important study milestone and witness the commencement of Phase 2, with an enrollment target of 52 patients. We extend our heartfelt gratitude to our investigators, partners, and, most importantly, our patients for their invaluable participation in this critical study." The study abstract has been accepted by the ASCO GI and will be presented on January 19, 2024, San Francisco, California. About Ivaltinostat: Ivaltinostat, a novel anticancer therapeutic candidate that inhibits enzymatic activity of histone deacetylase, has been evaluated for solid tumors and hematologic malignancies. About CG Pharmaceuticals: CG Pharmaceuticals, a wholly owned U.S. subsidiary of CG Invites, is dedicated to advancing innovative therapies to improve the lives of patients with cancer. Forward-Looking Statement Disclosure: This press release may contain certain forward-looking statements relating to the goals, business strategy, financial and market position, product development, and projections for the Company. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statements can be guaranteed, and actual results may differ. The information in this release is provided only as of the written date, and CG Pharmaceuticals undertakes no obligation to update any forward-looking statements contained in this release, except as required by law. CG Pharmaceuticals Contact: Douglas An Head of Finance and IR representative douglas.an@cgxinc.com SOURCE CG Pharmaceuticals, Inc.

临床2期

100 项与 Ivaltinostat 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12259

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
转移性胰腺腺癌	临床2期	美国	CG Pharmaceuticals, Inc.	2022-08-15
急性髓性白血病	临床2期	韩国	CG Invites Co., Ltd.	2022-01-30
新型冠状病毒感染	临床2期	韩国	CG Invites Co., Ltd.	2022-01-30
肝细胞癌	临床2期	韩国	CG Invites Co., Ltd.	2022-01-30
骨髓增生异常综合征	临床2期	韩国	CG Invites Co., Ltd.	2022-01-30
胰腺导管腺癌	临床2期	韩国	CG Invites Co., Ltd.	2022-01-30
特发性肺纤维化	临床前	美国	CG Invites Co., Ltd.	2023-01-03
晚期恶性实体瘤	临床前	韩国	CG Invites Co., Ltd.	2010-09-01
晚期胰腺腺癌	药物发现	韩国	CG Invites Co., Ltd.	2016-03-01
胰腺继发性恶性肿瘤	药物发现	韩国	CG Invites Co., Ltd.	2016-03-01

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


SP071 (ERA2018)	N/A	高血压	-	CG200745	(簾襯廠觸觸積醖襯遞艱) = 醖遞襯膚襯膚繭鹹鹽膚餘窪醖艱鏇觸糧簾糧壓 (襯餘衊膚遞構選築繭蓋 )	积极	2018-05-18
SP071 (ERA2018)	N/A	高血压	-	CG200745	(簾襯廠觸觸積醖襯遞艱) = 齋製積膚鬱淵簾淵獵憲餘窪醖艱鏇觸糧簾糧壓 (襯餘衊膚遞構選築繭蓋 )	积极	2018-05-18
ASCO2012	临床1期	HR阳性/HER2低表达实体瘤	-	CG200745	(蓋憲壓積築鏇範淵獵鹹) = 鏇衊鑰繭繭鑰積壓鏇願齋選築廠艱觸網繭壓簾 (構夢廠艱製鑰鹹淵築築 ) 更多	-	2012-05-20