Evidence map›Paper›PMID 38054726›Full record

ArticleAntimicrobial agents and chemotherapy2024

First-in-human study to evaluate the safety, tolerability, and population pharmacokinetic/pharmacodynamic target attainment analysis of FL058 alone and in combination with meropenem in healthy subjects.

Zhiwei Huang, Xinyi Yang, Yi Jin, Jicheng Yu, Guoying Cao, Jingjing Wang, Yingying Hu, Jingyi Dai, Jufang Wu, Qiong Wei and 11 more

3 registry-linked trialsOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
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.

NCT05055687 phase1completednot on this map

A Randomized, Double-Blind, Single- Multiple Dose, Placebo-Controlled Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of FL058 for Injection in Healthy Chinese Subjects.

TypeinterventionalSponsorQilu Pharmaceutical Co., Ltd.Ran2020 to 2020Enrolled20ConditionsHealthyArmsFL058, Placebo
NCT05058105 phase1completednot on this map

A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single- and Multiple Ascending-dose Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous FL058 and Meropenem Alone and in Combination in Healthy Chinese Subjects

TypeinterventionalSponsorQilu Pharmaceutical Co., Ltd.Ran2020 to 2021Enrolled40ConditionsHealthyArmsFL058 500mg and Meropenem 1000mg（ IV 120min）, FL058 Placebo and Meropenem 1000mg（ IV 120min）, FL058 1000mg（ IV 120min）, FL058 Placebo （ IV 120min）, Meropenem 1000 mg （ IV 120min）
NCT05058118 phase1completednot on this map

A Randomized, Double-Blind, Single-Dose, Placebo-Controlled Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of FL058 for Injection in Healthy Chinese Subjects.

TypeinterventionalSponsorQilu Pharmaceutical Co., Ltd.Ran2019 to 2020Enrolled54ConditionsHealthyArmsFL058, Placebo
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 8 citations in OpenAlex.

  1. Disarming carbapenemase-producingAntimicrobial agents and chemotherapy · 2026
    Article
  2. In vitro activity of the novel β-lactamase inhibitor FL058 combined with meropenem against KPC- or NDM-producing enterobacterales and Pseudomonas aeruginosa.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025
    Article
  3. Article
  4. Review
  5. Frontiers in pharmacology · 2024
    Article
  6. Article
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

21 authors at 2 institutions in 1 country.

Zhiwei Huang *Phase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.ORCID 0000-0002-7767-5167
Xinyi Yang *Phase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Yi JinPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Jicheng YuPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Guoying CaoPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Jingjing WangPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Yingying HuPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Jingyi DaiPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Jufang WuPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Qiong WeiPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Yan TianPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Shuyan YuPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Xu ZhuPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Xiaomeng MaoPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Wei LiuPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Hong LiangPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.
Shansong ZhengQilu Pharmaceutical Co. Ltd. , Jinan, China.
Yunfei JuQilu Pharmaceutical Co. Ltd. , Jinan, China.
Zenghua WangQilu Pharmaceutical Co. Ltd. , Jinan, China.
Jing ZhangPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.ORCID 0000-0003-2966-9149
Xiaojie WuPhase I Clinical Research Center, Huashan Hospital, Fudan University , Shanghai, China.ORCID 0000-0002-0081-6507
Fudan University · CNLuye Pharma (China) · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

FL058 is a novel diazabicyclooctane β-lactamase inhibitor. This first-in-human study evaluated the safety, tolerability, and population pharmacokinetic (PK)/pharmacodynamic target attainment analysis of FL058 alone and in combination with meropenem in healthy subjects. The results showed that the maximum tolerated dose of FL058 was 3,000 mg after single-dose infusion. FL058 in combination with meropenem did not cause any grade 3 or higher adverse event when the dose was escalated up to 1,000 mg/2,000 mg. FL058 exposure PK parameters showed dose proportionality. FL058 was excreted primarily in urine. No significant PK interaction was found between FL058 and meropenem. Population PK model analysis indicated that the PK profiles of FL058 and meropenem were consistent with the two-compartment model. The impact of covariates, creatinine clearance, concomitant use of meropenem, body weight, sex, and FL058 dose, on FL058 exposure was less than 10%. FL058/meropenem combination was safe and well tolerated up to a 1,000-mg/2,000-mg dose in healthy adults. The recommended minimum dose of FL058/meropenem combination was 500 mg/1,000 mg by intravenous infusion over 2 h every 8 h based on target attainment analysis. The good safety, tolerability, and satisfactory PK profiles of FL058 alone and in combination with meropenem in this first-in-human study will support further clinical development of FL058 in combination with meropenem in patients with target infections (ClinicalTrials.gov identifiers: NCT05055687, NCT05058118, and NCT05058105).

Indexed as

Anti-Bacterial Agentsbeta-Lactamase InhibitorsAdultHealthy VolunteersHumansInfusions, IntravenousMeropenemAnti-Bacterial Agentsbeta-Lactamase InhibitorsMeropenemfirst-in-human studyFL058population pharmacokineticssafetytarget attainment analysisβ-lactamase inhibitor

Identifiers

PMID38054726
PMCPMC10777830
OpenAlexW4389381205

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.