* ADOPTION

• Research type

  Research Study

• Full title

  A randomized, parallel group, multicentre, multinational, prospective, open-label exploratory study to evaluate the add-on effect of opicapone 50 mg or levodopa 100 mg as first strategy for the treatment of wearing-off in patients with Parkinson’s Disease.

• IRAS ID

  292370

• Contact name

  Camille Carroll

• Contact email

  camille.carroll@plymouth.ac.uk

• Sponsor organisation

  Bial - Portela & Ca, S.A.

• Eudract number

  2020-002754-24

• Clinicaltrials.gov Identifier

  NCT03959540

• Duration of Study in the UK

  1 years, 3 months, 0 days

• Research summary

  Summary of Research

  Parkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder characterized by motor and non-motor symptoms with progressive loss of autonomy that negatively impacts quality of life (QoL). The drug levodopa (L-DOPA) has been the gold standard for treatment of PD patients for more than 4 decades. The clinical benefit of L-DOPA progressively reduces, causing the return or a worsening of PD symptoms, a phenomenon called “wearing-off”. Over time, patients experience more and more hours per day in a disabling OFF-state. Patients may benefit from optimised L-DOPA therapy in conjunction with other drugs such as entacapone and tolcapone. Several randomised controlled trials have been conducted with opicapone administered as an adjunctive L-DOPA therapy. Treatment with opicapone was found to be effective in reducing the time patients are in an OFF-state and was well tolerated. As opposed to entacapone and tolcapone, opicapone does not require close laboratory monitoring or multiple oral administrations. Direct comparisons between increased doses of L-DOPA and the adding in of opicapone to treat wearing off have not been performed in previous studies. The goal of this study is to compare the add-on efficacy between opicapone 50 mg and an extra dose of levodopa 100 mg as first strategy for the treatment of wearing-off in subjects with PD.

  Summary of Results

  Bial Adoption study (BIA-91067-403) aimed to evaluate the efficacy, safety and tolerability of the addition of Opicapone 50 mg or an extra dose of Levodopa 100 mg to the existing Levodopa therapy, as first strategy for treating wearing-off in patients with Parkinson’s Disease (PD) and early motor fluctuations.

  A total of 106 subjects were screened and 75 subjects were randomly assigned to 1 of the 2 treatment groups, either oral Opicapone 50 mg (38 subjects) or Levodopa 100 mg (37 subjects).
  The study consisted of a 1-week screening period, a 4-week treatment period, and a 2-week post-study follow-up period. The total study duration was approximately 16 months.

  All 75 subjects assigned to treatment groups received at least 1 dose of the study treatment and were included in the Safety Analysis Set. A total of 53 patients were analyzed for efficacy in a dedicated statistical analysis named modified full analysis set (mFAS). This is because a total of 22 subjects were excluded due to protocol deviations, study treatment non-compliance or for not meeting the eligibility criteria.
  Overall, 72 (96.0%) of the 75 randomly assigned subjects completed the study, while 3 (4.0%) subjects dropped out permanently.

  Definitions:
  ON = Time when medication is providing benefit with regards to mobility, slowness, and stiffness.
  OFF = Time when medication has worn off and is no longer providing benefit with regards to mobility, slowness, and stiffness Dyskinesia = Involuntary twisting, turning movements. These movements are an effect of medication and occur during ON time:
  • Non-troublesome dyskinesia does not interfere with function or cause meaningful discomfort.
  • Troublesome dyskinesia interferes with function or causes meaningful discomfort.
  MDS-UPDRS = Movement Disorder Society-Unified Parkinson’s Disease Rating Scale MDS-NMS = Non-Motor Rating Scale CGI-I = Clinical Global Impression – Improvement Scale

  Primary Efficacy Endpoints:
  • Change in the OFF-Time
  Efficacy analyses revealed that both Opicapone 50 mg and Levodopa 100 mg treatment offered some extent of efficacy. No statistical differences were noted between Opicapone 50 mg and Levodopa 100 mg treatment groups in terms of OFF-time reduction.

  • Hauser’s Diary:
  At all study visits, the predominant state of the subjects was ‘ON without dyskinesia’ during the day and ‘asleep’ during the night. For very few subjects, the most predominant state was ‘ON with non-troublesome dyskinesia’ during the day and ‘ON without dyskinesia’ during the night. Overall, the results were comparable between both treatment groups.

  Secondary Efficacy Endpoints:
  Overall, the analysis of the secondary efficacy endpoints offered generally a trend favorable to the Opicapone 50 mg group against the Levodopa 100 mg group.

  Conclusions:
  Both Opicapone 50 mg and Levodopa 100 mg showed a clinical improvement in the primary efficacy endpoint (namely change in the OFF-time) with a higher trend favoring Opicapone treatment group in the modified full analysis set.
  The analyses of the mean change from baseline of the ON-time, percentage ON-time, MDS-UPDRS (Part III and IV), MDS-NMS and the improvements reported by the clinicians (CGI-I) in modified full analysis set were favorable to Opicapone over Levodopa group.
  Opicapone 50 mg once-daily oral dose was safe and well tolerated with no new safety signal reported for this population indicating an overall positive benefit-risk for its use Parkinson’s Disease patients.
  These results showed a clinical benefit of Opicapone 50 mg as adjunctive therapy to Levodopa in patients with underlying Parkinson’s Disease. To confirm the results reported in this study, a dedicated study in a larger sample size of Parkinson’s Disease patients is warranted

• REC name

  East Midlands - Leicester Central Research Ethics Committee

• REC reference

  22/EM/0184

• Date of REC Opinion

  27 May 2021

• REC opinion

  Further Information Favourable Opinion