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A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia

Svenningsson, Per ; Odin, Per LU ; Dizdar, Nil ; Johansson, Anders ; Grigoriou, Sotirios LU ; Tsitsi, Panagiota ; Wictorin, Klas LU ; Bergquist, Filip ; Nyholm, Dag LU and Rinne, Juha , et al. (2020) In Movement Disorders 35(6). p.1046-1054
Abstract

Background: IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. Objective: The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia. Methods: Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients’ regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days. Results: A total of 32 patients were randomized to treatment, and... (More)

Background: IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. Objective: The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia. Methods: Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients’ regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days. Results: A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 μM on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa. Conclusions: IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
apathy, axial symptom, cognition, fall, movement disorder
in
Movement Disorders
volume
35
issue
6
pages
9 pages
publisher
John Wiley and Sons
external identifiers
  • scopus:85082037620
  • pmid:32198802
ISSN
0885-3185
DOI
10.1002/mds.28020
language
English
LU publication?
yes
id
2b8df4c0-3b04-413a-841c-d7f4cd4c2e96
date added to LUP
2020-04-09 08:52:47
date last changed
2021-03-03 05:19:00
@article{2b8df4c0-3b04-413a-841c-d7f4cd4c2e96,
  abstract     = {<p>Background: IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex. Objective: The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia. Methods: Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients’ regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days. Results: A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 μM on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa. Conclusions: IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia.</p>},
  author       = {Svenningsson, Per and Odin, Per and Dizdar, Nil and Johansson, Anders and Grigoriou, Sotirios and Tsitsi, Panagiota and Wictorin, Klas and Bergquist, Filip and Nyholm, Dag and Rinne, Juha and Hansson, Fredrik and Sonesson, Clas and Tedroff, Joakim},
  issn         = {0885-3185},
  language     = {eng},
  number       = {6},
  pages        = {1046--1054},
  publisher    = {John Wiley and Sons},
  series       = {Movement Disorders},
  title        = {A Phase 2a Trial Investigating the Safety and Tolerability of the Novel Cortical Enhancer IRL752 in Parkinson's Disease Dementia},
  url          = {http://dx.doi.org/10.1002/mds.28020},
  doi          = {10.1002/mds.28020},
  volume       = {35},
  year         = {2020},
}