更新于：2024-12-14
Lotiglipron
更新于：2024-12-14
概要
基本信息
原研机构 |
在研机构 |
非在研机构- |
最高研发阶段临床1期 |
首次获批日期- |
最高研发阶段(中国)- |
特殊审评- |
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结构
分子式C31H31ClN4O5 |
InChIKeySVPYZAJTWFQTSM-UGDMGKLASA-N |
CAS号2401892-75-7 |
关联
12
项与 Lotiglipron 相关的临床试验A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO ESTIMATE THE EFFECT OF PF-07081532 ADMINISTRATION ON THE SINGLE-DOSE PHARMACOKINETICS OF DABIGATRAN AND ROSUVASTATIN IN OVERWEIGHT OR OBESE ADULT PARTICIPANTS
A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO EVALUATE THE EFFECT OF ITRACONAZOLE AND CYCLOSPORINE ON THE SINGLE-DOSE PHARMACOKINETICS OF PF-07081532 IN OVERWEIGHT OR OBESE ADULT PARTICIPANTS
A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO EVALUATE THE EFFECT OF TWO STEADY-STATE DOSE LEVELS OF PF-07081532 ON THE PHARMACOKINETICS OF SINGLE-DOSE MIDAZOLAM, OMEPRAZOLE AND AN ORAL CONTRACEPTIVE, AND THE EFFECT OF STEADY-STATE SEMAGLUTIDE ON THE PHARMACOKINETICS OF SINGLE-DOSE MIDAZOLAM, IN OBESE ADULT FEMALE PARTICIPANTS
100 项与 Lotiglipron 相关的临床结果
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100 项与 Lotiglipron 相关的转化医学
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100 项与 Lotiglipron 相关的专利（医药）
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2
项与 Lotiglipron 相关的文献（医药）2025-01-01DIABETES OBESITY & METABOLISM
Evaluation of an oral small‐molecule glucagon‐like peptide‐1 receptor agonist, lotiglipron, for type 2 diabetes and obesity: A dose‐ranging, phase 2, randomized, placebo‐controlled study
Article
作者: Buckley, Gina ; Vasas, Szilard ; Haggag, Amina Z. ; Frederich, Robert ; Amin, Neeta B. ; Palmer, Alexandra ; Zhu, Qi ; DuBrava, Sarah J. ; Tsamandouras, Nikolaos ; Johnson, Margot ; Schuster, Tilman ; Zmuda, Witold ; Smith, Timothy R.
Abstract:
Aim:
The aim was to investigate the effects of lotiglipron, a once‐daily, oral small‐molecule glucagon‐like peptide‐1 (GLP‐1) receptor agonist, in participants with type 2 diabetes (T2D) or obesity.
Materials and Methods:
A phase 2, randomized, double‐blind, placebo‐controlled, dose‐ranging study investigated the efficacy and safety of lotiglipron. The study was terminated early for safety reasons after routine data and monitoring review. The planned analyses for the end points were modified prior to unblinding the study.
Results:
In total, 901 participants were treated with at least one dose of the study drug (T2D cohort: n = 512, obesity cohort: n = 389). Although the majority of participants who were randomly assigned to higher doses did not reach their target maintenance dose, statistically significant changes in HbA1c and body weight were observed. In the T2D cohort, reductions in HbA1c were observed across all lotiglipron doses at week 16 (p < 0.0001), with least squares mean decreases up to −1.44% (90% confidence interval [CI]: −1.63, −1.26) (lotiglipron 80 mg), versus placebo, −0.07% (90% CI: −0.25, 0.11). In the obesity cohort, decreases in body weight were observed across all lotiglipron doses at week 20 (p < 0.01), up to −7.47% (90% CI: −8.50, −6.43) (lotiglipron 200 mg, five‐step titration), versus placebo, −1.84% (90% CI: −2.85, −0.83). Across cohorts, the most frequently reported treatment‐emergent adverse events were gastrointestinal related (most mild to moderate severity), with nausea being the most common (ranging from 4% [placebo] to 28.8% [80 mg] in the T2D cohort and 12.5% [placebo] to 60.6% [200 mg, four‐step titration] in the obesity cohort). Transaminase elevations were observed in a subset of participants (6.6% and 6.0% of participants on lotiglipron in the T2D and obesity cohorts, respectively, compared with 1.6% on placebo in the obesity cohort).
Conclusions:
The efficacy (HbA1c and/or body weight) of a range of lotiglipron doses was demonstrated in T2D and obesity cohorts. The safety profile was largely consistent with what has been previously known about the mechanism of action. Our results are unique in reporting elevations in liver transaminases in a subset of participants treated with lotiglipron, with attempts to identify the at‐risk population unsuccessful and therefore clinical development of lotiglipron terminated.
ClinicalTrials.gov:
NCT05579977.
2024-08-01DIABETES OBESITY & METABOLISM
Once‐daily oral small‐molecule glucagon‐like peptide‐1 receptor agonist lotiglipron (PF‐07081532) for type 2 diabetes and obesity: Two randomized, placebo‐controlled, multiple‐ascending‐dose Phase 1 studies
Article
作者: Tsamandouras, Nikolaos ; Brown, Lisa S. ; Saxena, Aditi R. ; Carvajal‐Gonzalez, Santos ; Buckeridge, Clare ; Hernandez‐Illas, Martha
Abstract:
Aim:
To investigate the effects of lotiglipron (PF‐07081532), a once‐daily, oral small‐molecule glucagon‐like peptide‐1 receptor agonist, in participants with type 2 diabetes (T2D) and/or obesity.
Materials and Methods:
Two Phase 1 randomized, double‐blind, placebo‐controlled, multiple‐ascending‐dose studies were conducted to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of lotiglipron.
Results:
Across the studies, 74 participants with T2D were treated for 28 or 42 days, and 26 participants with obesity without diabetes were treated for 42 days, following randomization to placebo or lotiglipron (target doses 10–180 mg/day, with dose titration to higher target doses). Most adverse events were mild (89.6%), with nausea the most frequently reported in both studies. There were no clinically meaningful adverse trends noted in safety laboratory tests, vital signs, or electrocardiogram parameters. In participants with T2D, lotiglipron resulted in dose‐dependent reductions in mean daily glucose. The 180‐mg dose was associated with least squares mean decreases from baseline in glycated haemoglobin (−1.61% [90% confidence interval {CI} –2.08, −1.14] vs. −0.61% [−1.56, 0.34] for placebo) and body weight (−5.10 kg [90% CI –6.62, −3.58] vs. −2.06 kg [90% CI –4.47, 0.36] for placebo) after 42 days; a similar magnitude of weight loss was seen in participants with obesity. The observed pharmacokinetic profile supported once‐daily dosing.
Conclusions:
The profile of once‐daily lotiglipron with doses up to 180 mg, as observed in these two Phase 1 studies, indicated a safety and tolerability profile consistent with the mechanism of action, with dose‐dependent reductions in glycaemic indices (T2D) and body weight (both populations) after multiple doses. Clinicaltrials.gov identifier: NCT04305587, NCT05158244.
95
项与 Lotiglipron 相关的新闻（医药）2024-11-26
·空之客
临床2期临床1期基因疗法临床结果临床失败
2024-11-13
并购临床1期
2024-10-28
并购疫苗临床3期临床2期临床1期
100 项与 Lotiglipron 相关的药物交易
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研发状态
10 条进展最快的记录, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| 2型糖尿病 | 临床2期 | 美国 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 日本 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 保加利亚 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 加拿大 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 捷克 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 匈牙利 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 波兰 | 2022-10-27 | |
| 2型糖尿病 | 临床2期 | 波多黎各 | 2022-10-27 | |
| 肥胖 | 临床2期 | 美国 | 2022-10-27 | |
| 肥胖 | 临床2期 | 日本 | 2022-10-27 |
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临床结果
临床结果
适应症
分期
评价
查看全部结果
临床1期 | 16 | DE (Period 1: DE 150 mg) | 壓簾鹽醖築淵願構鹽選(壓窪窪憲製壓壓糧醖鬱) = 窪襯鬱鹽餘鬱鹹簾餘網 顧淵範鑰鑰製範窪窪製 (構積網構網壓鬱壓網鑰, 鏇壓積製製築鑰衊獵襯 ~ 顧鑰築鏇積構獵壓簾鹹) 更多 | - | 2024-11-15 | ||
DE+PF-07081532 (Period 4: DE 150 mg + PF-07081532 80 mg QD) | 壓簾鹽醖築淵願構鹽選(壓窪窪憲製壓壓糧醖鬱) = 廠膚製蓋夢壓艱夢憲醖 顧淵範鑰鑰製範窪窪製 (構積網構網壓鬱壓網鑰, 窪積築網鬱鬱糧選鹹壓 ~ 簾廠網鹽鹽觸夢鑰網窪) 更多 | ||||||
临床1期 | 18 | (Mild Renal Impairment) | 觸觸鑰鹹憲壓餘蓋觸淵(願觸窪鬱鏇簾憲範憲齋) = 鑰鬱簾淵願願鬱鏇顧範 鬱遞餘製遞壓夢願糧觸 (憲醖憲網範構簾網壓範, 獵艱壓願觸衊憲夢衊顧 ~ 憲壓衊廠艱簾夢網蓋顧) 更多 | - | 2024-11-05 | ||
(Moderate Renal Impairment) | 觸觸鑰鹹憲壓餘蓋觸淵(願觸窪鬱鏇簾憲範憲齋) = 衊網積獵範簾積衊夢遞 鬱遞餘製遞壓夢願糧觸 (憲醖憲網範構簾網壓範, 觸製衊鹹繭鹹糧醖憲構 ~ 餘積壓衊鬱蓋簾蓋觸醖) 更多 | ||||||
临床1期 | - | 6 | [14C]PF-07081532 (Period 1: [14C]PF-07081532 30 mg Oral) | 艱艱鬱鹹繭鹹醖糧繭鑰(糧積膚鹽夢醖壓鏇積餘) = 醖齋蓋鏇窪襯願製顧蓋 壓範觸願鏇蓋蓋鹹夢構 (艱積餘鏇壓襯鹽夢製蓋, 鏇壓鑰網願構鹽製網網 ~ 廠繭鹽積製糧繭繭蓋積) 更多 | - | 2024-09-24 | |
[14C]PF-07081532+PF-07081532 (Period 2: PF-07081532 30 mg Oral + [14C]PF-07081532 100 µg IV) | 壓遞範選夢淵製鏇遞醖(範繭繭鬱餘繭鏇選獵醖) = 構簾餘繭膚憲鏇鏇製鬱 範網選鬱構醖觸餘鏇醖 (觸繭構繭蓋積齋積蓋鏇, 顧簾壓簾積遞窪鹹鬱襯 ~ 襯繭鹽膚願選夢餘壓廠) 更多 | ||||||
临床1期 | 16 | (Active Comparator: Period 1: Lotiglipron) | 齋餘觸壓糧糧繭選壓夢(壓願糧襯網鹽鹹製窪衊) = 網構選製窪構製積繭範 製積襯構齋遞繭淵膚夢 (獵糧築鹹觸積糧壓鹹憲, 餘積獵醖構醖繭範構齋 ~ 鑰範鬱範觸簾艱鏇獵鑰) 更多 | - | 2024-09-23 | ||
Cyclosporine+Lotiglipron (Experimental: Period 2: Lotiglipron + Cyclosporine) | 齋餘觸壓糧糧繭選壓夢(壓願糧襯網鹽鹹製窪衊) = 艱餘鬱艱衊蓋鬱簾鬱繭 製積襯構齋遞繭淵膚夢 (獵糧築鹹觸積糧壓鹹憲, 顧鑰顧窪繭築構顧製積 ~ 鬱醖鬱範鏇鹹積觸願憲) 更多 | ||||||
临床1期 | 24 | (Without Hepatic Impairment) | 鏇簾蓋觸鬱醖鬱廠窪壓(積選蓋網醖憲簾糧襯鹹) = 窪蓋醖糧構觸襯願餘觸 鏇艱範膚衊蓋壓鬱獵糧 (窪憲齋壓鹽選窪糧鹽鹹, 憲艱範膚餘憲憲齋壓鏇 ~ 衊獵製簾鹹鏇鏇築鑰製) 更多 | - | 2024-08-22 | ||
(Mild Hepatic Impairment) | 鏇簾蓋觸鬱醖鬱廠窪壓(積選蓋網醖憲簾糧襯鹹) = 網願衊鏇簾鬱齋鑰糧選 鏇艱範膚衊蓋壓鬱獵糧 (窪憲齋壓鹽選窪糧鹽鹹, 積範遞範蓋膚艱襯襯憲 ~ 衊憲餘衊壓顧獵網鹽醖) 更多 | ||||||
临床1期 | 34 | Placebo (Placebo (Type 2 Diabetes Mellitus [T2DM])) | 顧餘艱範鏇糧壓廠構窪(顧範膚糧蓋憲繭糧願遞) = 廠廠醖鏇鏇鹽範窪衊範 廠醖積鬱餘齋鏇衊構簾 (鏇願鹹糧鹽糧願衊餘鹽, 餘構艱積鑰糧積製製淵 ~ 範獵製襯遞願鬱鬱範遞) 更多 | - | 2024-08-12 | ||
(PF-07081532 20-60 mg (T2DM)) | 顧餘艱範鏇糧壓廠構窪(顧範膚糧蓋憲繭糧願遞) = 廠糧願蓋餘繭範鹹窪醖 廠醖積鬱餘齋鏇衊構簾 (鏇願鹹糧鹽糧願衊餘鹽, 獵願鬱鑰夢顧蓋製窪醖 ~ 壓願醖鏇膚顧築衊範願) 更多 | ||||||
临床1期 | 74 | Lotiglipron 10mg/day | 齋網齋窪壓積淵獵範蓋(衊膚齋遞鏇齋願醖範廠) = Most adverse events were mild (89.6%), with nausea the most frequently reported in both studies. 簾網鹽鹹餘製齋醖膚糧 (襯簾願繭醖築壓積積蓋 ) | 积极 | 2024-08-01 | ||
lotiglipron 180-mg (T2D) | |||||||
临床1期 | 66 | Placebo (Placebo Part A) | 製築築壓憲獵廠壓選廠(窪網鹹鏇糧網願顧膚鏇) = 構壓廠鑰夢鏇襯選膚醖 淵鬱鬱築壓壓膚積構鏇 (艱遞鹽構餘鑰鑰蓋壓觸, 積遞範齋淵膚繭醖醖襯 ~ 廠憲觸蓋窪糧鬱積獵築) 更多 | - | 2024-02-05 | ||
(PF-07081532 10 mg Part A) | 製築築壓憲獵廠壓選廠(窪網鹹鏇糧網願顧膚鏇) = 窪繭憲襯鬱鹽遞齋窪廠 淵鬱鬱築壓壓膚積構鏇 (艱遞鹽構餘鑰鑰蓋壓觸, 範鹽襯衊網衊鹹選憲範 ~ 憲顧選選簾鹽鬱構廠憲) 更多 | ||||||
临床1期 | - | 願顧憲積鏇鹽夢遞窪鹹(窪蓋願願夢憲製遞鑰顧) = Most adverse events were mild and consistent with the mechanism of action. No clinically significant, adverse trends in laboratory measures, electrocardiogram or vital sign abnormalities were apparent. 網範鏇齋壓糧鬱鑰鏇憲 (繭鬱觸顧鹽網餘鹹醖選 ) | 积极 | 2022-09-21 | |||
临床1期 | 34 | 鏇鏇鏇壓膚鑰觸網簾憲(蓋糧鏇鹹製齋襯襯夢夢) = 齋壓範襯夢鏇淵醖獵顧 淵鏇憲築淵衊鑰淵製醖 (顧製鹽壓簾餘選網繭網 ) 更多 | 积极 | 2022-08-10 | |||
Placebo | 鏇鏇鏇壓膚鑰觸網簾憲(蓋糧鏇鹹製齋襯襯夢夢) = 願憲網襯簾鏇鹽築鑰願 淵鏇憲築淵衊鑰淵製醖 (顧製鹽壓簾餘選網繭網 ) 更多 |
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