First‐In‐Human Safety, Tolerability, and Pharmacokinetics of PPI‐1011, a Synthetic Plasmalogen Precursor
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...
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Wiley
2025-03-01
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| Series: | Clinical and Translational Science |
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| Online Access: | https://doi.org/10.1111/cts.70195 |
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| author | Tara Smith Kaeli J. Knudsen Shawn A. Ritchie |
| author_facet | Tara Smith Kaeli J. Knudsen Shawn A. Ritchie |
| author_sort | Tara Smith |
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| description | 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. |
| format | Article |
| id | doaj-art-8be416b2b80541e8b081752c723d006e |
| institution | DOAJ |
| issn | 1752-8054 1752-8062 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | Clinical and Translational Science |
| spelling | doaj-art-8be416b2b80541e8b081752c723d006e2025-08-20T02:49:40ZengWileyClinical and Translational Science1752-80541752-80622025-03-01183n/an/a10.1111/cts.70195First‐In‐Human Safety, Tolerability, and Pharmacokinetics of PPI‐1011, a Synthetic Plasmalogen PrecursorTara Smith0Kaeli J. Knudsen1Shawn A. Ritchie2Med‐Life Discoveries LP Saskatoon Saskatchewan CanadaMed‐Life Discoveries LP Saskatoon Saskatchewan CanadaMed‐Life Discoveries LP Saskatoon Saskatchewan CanadaABSTRACT 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.https://doi.org/10.1111/cts.70195Phase IPlasmalogen precursorPPI‐1011Rhizomelic chondrodysplasia punctata |
| spellingShingle | Tara Smith Kaeli J. Knudsen Shawn A. Ritchie First‐In‐Human Safety, Tolerability, and Pharmacokinetics of PPI‐1011, a Synthetic Plasmalogen Precursor Clinical and Translational Science Phase I Plasmalogen precursor PPI‐1011 Rhizomelic chondrodysplasia punctata |
| title | First‐In‐Human Safety, Tolerability, and Pharmacokinetics of PPI‐1011, a Synthetic Plasmalogen Precursor |
| title_full | First‐In‐Human Safety, Tolerability, and Pharmacokinetics of PPI‐1011, a Synthetic Plasmalogen Precursor |
| title_fullStr | First‐In‐Human Safety, Tolerability, and Pharmacokinetics of PPI‐1011, a Synthetic Plasmalogen Precursor |
| title_full_unstemmed | First‐In‐Human Safety, Tolerability, and Pharmacokinetics of PPI‐1011, a Synthetic Plasmalogen Precursor |
| title_short | First‐In‐Human Safety, Tolerability, and Pharmacokinetics of PPI‐1011, a Synthetic Plasmalogen Precursor |
| title_sort | first in human safety tolerability and pharmacokinetics of ppi 1011 a synthetic plasmalogen precursor |
| topic | Phase I Plasmalogen precursor PPI‐1011 Rhizomelic chondrodysplasia punctata |
| url | https://doi.org/10.1111/cts.70195 |
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