Evidence map›Paper›PMID 34807458›Full record

ArticleThe Prostate2022

Phase I clinical trial of HC-1119 soft capsule in Chinese healthy adult male subjects: Pharmacokinetics and safety of single-dose proportionality and effects of food.

Haiping Ma, Weidong Xu, Jin Ni, Naping Zhao, Shouyan Tang, Song Li, Tingting Cai, Jianping Xiu, Xin Kang, Shen Gao and 2 more

Abstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in The Prostate, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Haiping MaDepartment of Phase I Clinical Trial, Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, China.
Weidong XuDepartment of Urology, Changzheng Hospital, Naval Medical University, Shanghai, China.
Jin NiDepartment of Phase I Clinical Trial, Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, China.
Naping ZhaoDepartment of Phase I Clinical Trial, Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, China.
Shouyan TangDepartment of Urology, Changhai Hospital, Naval Medical University, Shanghai, China.
Song LiDepartment of Urology, Changhai Hospital, Naval Medical University, Shanghai, China.
Tingting CaiDepartment of Phase I Clinical Trial, Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, China.
Jianping XiuDepartment of Phase I Clinical Trial, Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, China.
Xin KangDepartment of Phase I Clinical Trial, Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, China.
Shen GaoDepartment of Phase I Clinical Trial, Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, China.
Li ZhangDepartment of Phase I Clinical Trial, Clinical Research Unit, Changhai Hospital, Naval Medical University, Shanghai, China.ORCID 0000-0003-1094-2192
Tie ZhouDepartment of Urology, Changhai Hospital, Naval Medical University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPreclinical studies showed that HC-1119, a deuterated version of enzalutamide, could competitively inhibit androgen binding to androgen receptor by blocking the transmission of androgen receptor signaling pathway as enzalutamide, inducing apoptosis of prostate cancer cells and reducing the proliferation of prostate cancer cells. Animal pharmacokinetic studies also show that deuterization of enzalutamide as HC-1119 could retain the basic properties of mother drug, increases the stability of compounds to metabolic enzymes and the drug exposure in vivo, prolong the half-life and reduce the production of metabolites, which may lead to a better efficacy and safety of HC-1119 compared with enzalutamide.

methodsTo evaluate the pharmacokinetics and safety of HC-1119 and the effects of food on pharmacokinetics in healthy adult Chinese men after single-dose administration of HC-1119. A total of 47 Chinese healthy adult male subjects received HC-1119 soft capsule at a single oral dose of 40, 80, or 160 mg followed on fasting or 160 mg after high-fat meal respectively. HC-1119 prototype and its metabolites M1 and M2 in plasma were collected individually in a total 23 time points. Pharmacokinetics were determined by sensitive LC/MS/MS for dose-proportionality study.

resultsIn subjects taking HC-1119 soft capsules on fasting, C

conclusionsHC-1119 is expected to have lower clinical dose than the similar drug enzalutamide. The absorption of HC-1119 and the main pharmacokinetic parameters of HC-1119 and its metabolites M1 and M2 were not affected by high-fat diet. The clinical application of HC-1119 soft capsule in the later stage can be recommended for both fasting and postprandial. The safety and tolerance were good in this population.

Indexed as

BenzamidesDrug StabilityFood-Drug InteractionsNitrilesPhenylthiohydantoinProstatic NeoplasmsAdministration, OralAdultAntineoplastic AgentsBiomarkers, PharmacologicalCapsulesCell ProliferationChinaDose-Response Relationship, DrugHalf-LifeHealthy VolunteersAntineoplastic AgentsBenzamidesBiomarkers, PharmacologicalCapsulesenzalutamideNitrilesPhenylthiohydantoinReceptors, AndrogenChinese healthy adult maledeuterated enzalutamidedose-proportionalityfood effectpharmacokinetics

Identifiers

PMID34807458
PMCPMC9298787

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.