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

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

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 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.

Detaljer

Författare
  • Per Svenningsson
  • Per Odin
  • Nil Dizdar
  • Anders Johansson
  • Sotirios Grigoriou
  • Panagiota Tsitsi
  • Klas Wictorin
  • Filip Bergquist
  • Dag Nyholm
  • Juha Rinne
  • Fredrik Hansson
  • Clas Sonesson
  • Joakim Tedroff
  • IRL752 Collaborators
Enheter & grupper
Externa organisationer
  • Karolinska Institute
  • Linköping University
  • Helsingborg Hospital
  • Göteborgs universitet
  • Uppsala universitet
  • Turku University Hospital
  • Clinical Trial Consultants AB (CTC AB)
  • Integrative Research Laboratories
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Neurologi
  • Farmakologi och toxikologi

Nyckelord

Originalspråkengelska
Sidor (från-till)1046-1054
Antal sidor9
TidskriftMovement Disorders
Volym35
Utgåva nummer6
Tidigt onlinedatum2020 mar 21
StatusPublished - 2020 jun
PublikationskategoriForskning
Peer review utfördJa