{"title":"First-In-Human Safety, Tolerability, and Pharmacokinetics of PPI-1011, a Synthetic Plasmalogen Precursor","authors":"Tara Smith, Kaeli J. Knudsen, Shawn A. Ritchie","doi":"10.1111/cts.70195","DOIUrl":null,"url":null,"abstract":"<p>PPI-1011 is a synthetic plasmalogen precursor designed to augment plasmalogen levels in patients with Rhizomelic chondrodysplasia punctata (RCDP), an ultra-rare genetic disorder caused by a plasmalogen deficiency that results in significant physical and mental delays. We report here a Phase I, randomized, double-blind, placebo-controlled study that evaluated the safety, tolerability, and pharmacokinetics (PK) of single (10–100 mg/kg) and multiple (75 and 100 mg/kg/day) ascending doses of PPI-1011 in healthy adults. All treatment-emergent adverse events (TEAEs) were mild, monitorable, and resolved without intervention, suggesting no significant safety concerns. The most common TEAEs were gastrointestinal in both the placebo and PPI-1011 groups, suggesting they were likely related to the oil-based nature of the formulation. PK analysis confirmed that both single (25, 50, 75 and 100 mg/kg) and multiple-dose (75 and 100 mg/kg, once daily) administration of PPI-1011 significantly increased serum levels of the target plasmalogen (PlsEtn 16:0/22:6). With a once-daily regimen, PPI-1011 administration resulted in a sustained increase of PlsEtn 16:0/22:6 serum concentrations in healthy participants over a duration of 14 days and beyond.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 3","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70195","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cts-Clinical and Translational Science","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cts.70195","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
PPI-1011 is a synthetic plasmalogen precursor designed to augment plasmalogen levels in patients with Rhizomelic chondrodysplasia punctata (RCDP), an ultra-rare genetic disorder caused by a plasmalogen deficiency that results in significant physical and mental delays. We report here a Phase I, randomized, double-blind, placebo-controlled study that evaluated the safety, tolerability, and pharmacokinetics (PK) of single (10–100 mg/kg) and multiple (75 and 100 mg/kg/day) ascending doses of PPI-1011 in healthy adults. All treatment-emergent adverse events (TEAEs) were mild, monitorable, and resolved without intervention, suggesting no significant safety concerns. The most common TEAEs were gastrointestinal in both the placebo and PPI-1011 groups, suggesting they were likely related to the oil-based nature of the formulation. PK analysis confirmed that both single (25, 50, 75 and 100 mg/kg) and multiple-dose (75 and 100 mg/kg, once daily) administration of PPI-1011 significantly increased serum levels of the target plasmalogen (PlsEtn 16:0/22:6). With a once-daily regimen, PPI-1011 administration resulted in a sustained increase of PlsEtn 16:0/22:6 serum concentrations in healthy participants over a duration of 14 days and beyond.
期刊介绍:
Clinical and Translational Science (CTS), an official journal of the American Society for Clinical Pharmacology and Therapeutics, highlights original translational medicine research that helps bridge laboratory discoveries with the diagnosis and treatment of human disease. Translational medicine is a multi-faceted discipline with a focus on translational therapeutics. In a broad sense, translational medicine bridges across the discovery, development, regulation, and utilization spectrum. Research may appear as Full Articles, Brief Reports, Commentaries, Phase Forwards (clinical trials), Reviews, or Tutorials. CTS also includes invited didactic content that covers the connections between clinical pharmacology and translational medicine. Best-in-class methodologies and best practices are also welcomed as Tutorials. These additional features provide context for research articles and facilitate understanding for a wide array of individuals interested in clinical and translational science. CTS welcomes high quality, scientifically sound, original manuscripts focused on clinical pharmacology and translational science, including animal, in vitro, in silico, and clinical studies supporting the breadth of drug discovery, development, regulation and clinical use of both traditional drugs and innovative modalities.