Long-term safety, tolerability and efficacy of apomorphine sublingual film in patients with Parkinson's disease complicated by OFF episodes: a phase 3, open-label study

J Neurol. 2024 Jun;271(6):3554-3570. doi: 10.1007/s00415-024-12323-2. Epub 2024 Mar 28.

Abstract

Background: Apomorphine sublingual film (SL-APO) is an on-demand treatment for OFF episodes in patients with Parkinson's disease (PD).

Objective: To assess the long-term (≥ 3 years) safety/tolerability and efficacy of SL-APO.

Methods: Study CTH-301 ( http://www.

Clinicaltrials: gov NCT02542696; registered 2015-09-03) was a phase 3, multicentre, open-label study of SL-APO in PD patients with motor fluctuations, comprised of a dose-titration and long-term safety phase. All participants received SL-APO. The primary endpoint was safety/tolerability (treatment-emergent adverse events [TEAEs]) during the long-term safety phase. Efficacy assessments included the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III (motor examination), assessed at weeks 24, 36 and 48 during the first year of the long-term safety phase.

Results: 496 patients were included and 120 (24.2%) completed the long-term safety phase. Mean duration of SL-APO exposure was 294.3 days. TEAEs related to study drug were experienced by 65.3% of patients (most common: nausea [6.0%], stomatitis [1.8%], lip swelling [1.8%], dizziness [1.6%], oral mucosal erythema [1.6%], mouth ulceration [1.6%]). TEAEs leading to study drug withdrawal were experienced by 34.0% of patients (most common: nausea [5.4%], lip swelling [4.5%], mouth ulceration [2.6%], stomatitis [2.3%]). A clinically meaningful reduction in MDS-UPDRS part III score was observed as soon as 15 min following administration of SL-APO, with peak effects observed approximately 30 min post-dose and sustained up to 90 min post-dose; results were consistent over 48 weeks.

Conclusions: SL-APO was generally well tolerated and efficacious over the long term as an on-demand treatment for OFF episodes in patients with PD.

Keywords: Apomorphine sublingual film; Motor fluctuations; OFF episodes; Parkinson’s disease.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Administration, Sublingual
  • Aged
  • Antiparkinson Agents* / administration & dosage
  • Antiparkinson Agents* / adverse effects
  • Apomorphine* / administration & dosage
  • Apomorphine* / adverse effects
  • Apomorphine* / pharmacology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease* / complications
  • Parkinson Disease* / drug therapy
  • Treatment Outcome

Substances

  • Apomorphine
  • Antiparkinson Agents