Safety and tolerability of IRL790 in Parkinson’s disease with levodopa-induced dyskinesia—a phase 1b trial

Abstract

IRL790 is a novel compound with psychomotor stabilizing properties primarily targeting the dopamine D3 receptor. IRL790 is developed as an experimental treatment for levodopa-induced dyskinesia (LID), impulse control disorder, and psychosis in Parkinson’s disease (PD). The primary objective was to investigate the safety and tolerability of IRL790 in PD patients with LID in a randomized controlled trial. PD patients with peak-dose dyskinesia were randomized to placebo or IRL790 treatment (1:3 ratio) for 4 weeks. Study drug was given as an adjunct treatment to the patients’ regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days, whereafter dosing was kept stable for an additional 14 days. Fifteen patients were randomized to treatment and 13 patients completed the 4-week treatment. Adverse events were mostly reported during the titration phase of the trial. They were mainly central nervous system related and could be mitigated by dose adjustments. There were no serious adverse events. There were no clinically significant changes in vital signs, electrocardiogram, and laboratory parameters due to the treatment. The average dose in the stable dose phase was 18 mg daily, yielding a 2-h post-dose plasma concentration of average 229 nM on day 28. Assessments for motor function showed a numeric reduction in dyskinesia. It is concluded that IRL790 can be safely administered to patients with advanced PD. The results will be of guidance for the design of phase 2 studies.

Helicobacter pylori Eradication in Parkinson's Disease: A Randomized Placebo‐Controlled Trial

“…They have also been suggested to have greater sensitivity to detect subtle clinical changes 29,30 and were included as a novel feature in our trial protocol because of this possibility. To our knowledge, this study is among the first few RCTs in PD using wearable sensor data as outcome measures 31 . This is also the only study of HP eradication in PD to investigate, a priori, the possible role of concomitant SIBO.…”

Pathophysiological Mechanisms and Experimental Pharmacotherapy for L-Dopa-Induced Dyskinesia

“… 125 A phase Ib study with mesdopetam as an adjunct treatment to regular antiparkinsonian medication in 15 PD patients experiencing peak-dose dyskinesia showed a median UDysRS score reduction of 11.5 points vs placebo. 126 In 2019, a randomized, double-blind, placebo-controlled, multicenter phase IIa study on the efficacy and tolerability of mesdopetam was carried out in 74 PD patients with LID on stable antiparkinsonian medication (ClinicalTrials.gov identifier: NCT03368170). The study showed a meaningful reduction in LID severity as assessed by UDysRS, UPDRS part IV, and patient-reported diaries (Hauser diaries), and no side effects were reported.…”

Effects of a Novel Psychomotor Stabilizer, IRL790, on Biochemical Measures of Synaptic Markers and Neurotransmission

“…IRL790 is developed for treatment of complications associated with therapy in PD, primarily LIDs. In fact, there is preliminary data that IRL790 counteracts LIDs in PD patients (Svenningsson et al, 2018), and IRL790 shows clear antidyskinetic effects in rats (Waters et al, 2020). Studies have reported a higher mortality rate toward dopaminergic lesioning by 6-hydroxydopamine in mice than rats (Lundblad et al, 2004).…”

“…IRL790 is developed for treatment of complications associated with therapy in Parkinson disease (PD). It is safe and tolerable in PD patients and appears to counteract levodopa-induced dyskinesias (LIDs) (Svenningsson et al, 2018). IRL790 is currently in a clinical phase 2 efficacy study for LID in PD.…”