A first‐in‐human oral dose study of mesdopetam (IRL790) to assess its safety, tolerability, and pharmacokinetics in healthy male volunteers
Abstract The management of Parkinson's disease (PD) is frequently compromised by complications induced by dopaminergic treatment such as involuntary movements (dyskinesias) and psychosis. Mesdopetam (IRL790) is a novel dopamine D3 receptor antagonist developed for the management of complication...
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| Format: | Article |
| Language: | English |
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Wiley
2021-05-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.792 |
| _version_ | 1818741423131852800 |
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| author | Folke Sjöberg Susanna Waters Boel Löfberg Clas Sonesson Nicholas Waters Joakim Tedroff |
| author_facet | Folke Sjöberg Susanna Waters Boel Löfberg Clas Sonesson Nicholas Waters Joakim Tedroff |
| author_sort | Folke Sjöberg |
| collection | DOAJ |
| description | Abstract The management of Parkinson's disease (PD) is frequently compromised by complications induced by dopaminergic treatment such as involuntary movements (dyskinesias) and psychosis. Mesdopetam (IRL790) is a novel dopamine D3 receptor antagonist developed for the management of complications of therapy in PD. This study evaluated the safety, tolerability, and pharmacokinetics of escalating single and multiple doses of mesdopetam. We conducted a prospective, single‐center, randomized, double‐blind, placebo‐controlled phase I, and first‐in‐human (FIH) study with mesdopetam administered to healthy male subjects. Overall, mesdopetam was well‐tolerated up to a 120 mg single dose and up to 80 mg upon multiple dosing. Adverse events (AEs) were mainly related to the nervous system and were dose‐dependent. No serious adverse events occurred and no AEs led to withdrawal. The results of the single‐ascending‐dose and multiple‐ascending‐dose parts indicated dose‐ and time‐independent pharmacokinetics with rapid absorption and maximum plasma levels that were generally reached within 2 h after dosing. No accumulation was observed upon multiple dosing. It is concluded that mesdopetam was safe and well‐tolerated in healthy male volunteers. Pharmacokinetic analysis indicated rapid absorption and dose‐linear pharmacokinetics of mesdopetam, with a plasma half‐life of around 7 h, upon single and repeated dosing. The pharmacokinetics of mesdopetam supports twice‐daily use in patients. |
| first_indexed | 2024-12-18T01:56:23Z |
| format | Article |
| id | doaj.art-287aae86fd3f4466a3d910fdf394b552 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-12-18T01:56:23Z |
| publishDate | 2021-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-287aae86fd3f4466a3d910fdf394b5522022-12-21T21:24:53ZengWileyPharmacology Research & Perspectives2052-17072021-05-0193n/an/a10.1002/prp2.792A first‐in‐human oral dose study of mesdopetam (IRL790) to assess its safety, tolerability, and pharmacokinetics in healthy male volunteersFolke Sjöberg0Susanna Waters1Boel Löfberg2Clas Sonesson3Nicholas Waters4Joakim Tedroff5Clinical Trials Consultants AB Uppsala SwedenIntegrative Research Laboratories AB Gothenburg SwedenIntegrative Research Laboratories AB Gothenburg SwedenIntegrative Research Laboratories AB Gothenburg SwedenIntegrative Research Laboratories AB Gothenburg SwedenIntegrative Research Laboratories AB Gothenburg SwedenAbstract The management of Parkinson's disease (PD) is frequently compromised by complications induced by dopaminergic treatment such as involuntary movements (dyskinesias) and psychosis. Mesdopetam (IRL790) is a novel dopamine D3 receptor antagonist developed for the management of complications of therapy in PD. This study evaluated the safety, tolerability, and pharmacokinetics of escalating single and multiple doses of mesdopetam. We conducted a prospective, single‐center, randomized, double‐blind, placebo‐controlled phase I, and first‐in‐human (FIH) study with mesdopetam administered to healthy male subjects. Overall, mesdopetam was well‐tolerated up to a 120 mg single dose and up to 80 mg upon multiple dosing. Adverse events (AEs) were mainly related to the nervous system and were dose‐dependent. No serious adverse events occurred and no AEs led to withdrawal. The results of the single‐ascending‐dose and multiple‐ascending‐dose parts indicated dose‐ and time‐independent pharmacokinetics with rapid absorption and maximum plasma levels that were generally reached within 2 h after dosing. No accumulation was observed upon multiple dosing. It is concluded that mesdopetam was safe and well‐tolerated in healthy male volunteers. Pharmacokinetic analysis indicated rapid absorption and dose‐linear pharmacokinetics of mesdopetam, with a plasma half‐life of around 7 h, upon single and repeated dosing. The pharmacokinetics of mesdopetam supports twice‐daily use in patients.https://doi.org/10.1002/prp2.792dopamine D receptorlevodopa dyskinesiaParkinson's diseasepsychosis |
| spellingShingle | Folke Sjöberg Susanna Waters Boel Löfberg Clas Sonesson Nicholas Waters Joakim Tedroff A first‐in‐human oral dose study of mesdopetam (IRL790) to assess its safety, tolerability, and pharmacokinetics in healthy male volunteers Pharmacology Research & Perspectives dopamine D receptor levodopa dyskinesia Parkinson's disease psychosis |
| title | A first‐in‐human oral dose study of mesdopetam (IRL790) to assess its safety, tolerability, and pharmacokinetics in healthy male volunteers |
| title_full | A first‐in‐human oral dose study of mesdopetam (IRL790) to assess its safety, tolerability, and pharmacokinetics in healthy male volunteers |
| title_fullStr | A first‐in‐human oral dose study of mesdopetam (IRL790) to assess its safety, tolerability, and pharmacokinetics in healthy male volunteers |
| title_full_unstemmed | A first‐in‐human oral dose study of mesdopetam (IRL790) to assess its safety, tolerability, and pharmacokinetics in healthy male volunteers |
| title_short | A first‐in‐human oral dose study of mesdopetam (IRL790) to assess its safety, tolerability, and pharmacokinetics in healthy male volunteers |
| title_sort | first in human oral dose study of mesdopetam irl790 to assess its safety tolerability and pharmacokinetics in healthy male volunteers |
| topic | dopamine D receptor levodopa dyskinesia Parkinson's disease psychosis |
| url | https://doi.org/10.1002/prp2.792 |
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