eArly levoDopa With Opicapone in Parkinson's paTients wIth motOr fluctuatioNs. (ADOPTION)

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.

This is a randomized, parallel group, multicentre, multinational, prospective, open-label exploratory study in Parkinson's disease (PD) patients to evaluate the add-on efficacy of opicapone 50 mg or an extra dose of levodopa (L-DOPA) 100 mg as first strategy for the treatment of wearing-off.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: Opicapone; Drug: L-DOPA/DDCI

Detailed Description

The study consists of a one-week screening period, four weeks of open-label treatment and two weeks of post-study follow-up. The total study duration for each patient will be approximately 7 weeks

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13187
    • Praxis Dr. med. Kirsten Hahn
  • Berlin, Germany, 12203
    • Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
  • Baden Wuerttemberg
    • Freiburg, Baden Wuerttemberg, Germany, 79106
      • Universitaetsklinikum Freiburg
    • Wolfach, Baden Wuerttemberg, Germany, 77723
      • Parkinson-Klinik Ortenau GmbH&Co KG
  • Bayern
    • Haag in Oberbayern, Bayern, Germany, 83527
      • Klinik Haag i. OB
    • Wuerzburg, Bayern, Germany, 97080
      • Universitaetsklinikum Wuerzburg
  • Thueringen
    • Gera, Thueringen, Germany, 07551
      • Praxis Dr. Oehlwein
    • Stadtroda, Thueringen, Germany, 07646
      • Asklepios Fachklinikum Stadtroda
• Italy
  • Milano, Italy, 20122
    • Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
  • Napoli, Italy, 80138
    • Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"
  • Pisa, Italy, 56126
    • Azienda Ospedaliero Universitaria Pisana
  • Terni, Italy, 05100
    • Azienda Ospedaliera Santa Maria di Terni
• Portugal
  • Lisboa
    • Loures, Lisboa, Portugal, 2674-514
      • Hospital Beatriz Angelo
    • Torres Vedras, Lisboa, Portugal, 2560-280
      • CNS-Campus Neurologico Senior
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28034
    • Hospital Ruber Internacional
  • Ourense, Spain, 32005
    • Complejo Hospitalario Universitario de Orense
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche
  • Barcelona
    • Sant Joan Despí, Barcelona, Spain, 08041
      • Hospital de Sant Joan Despí Moisès Broggi
  • La Coruña
    • A Coruña, La Coruña, Spain, 15006
      • Complejo Hospitalario Universitario A Coruña
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
• United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom, EX2 5DW
      • Royal Devon and Exeter Hospital (Wonford)
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • University Hospitals Plymouth
  • Greater London
    • London, Greater London, United Kingdom, SE5 9RS
      • King's College Hospital
  • Tyne & Wear
    • Newcastle Upon Tyne, Tyne & Wear, United Kingdom, NE4 5PL
      • Newcastle University- Clinical Ageing Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to comprehend and willing to sign an informed consent form and to comply with all aspects of the study.
2. Male or female patients aged 30 years or older.
3. Diagnosed with idiopathic PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria (2006) or according to the Movement Disorder Society (MDS) Clinical Diagnostic Criteria (2015).
4. Disease severity Stages I-III (Hoehn & Yahr staging) at ON.
5. Treated on a stable regimen for at least four weeks before screening with immediate-release L-DOPA/DDCI, three to four intakes per day, and up to maximum daily dose of 600 mg L-DOPA.
6. In case of any other anti-PD-treatments, they should be on a stable regimen for at least four weeks before screening, and not likely to need any adjustment during the study.
7. Signs of wearing-off phenomenon with average total daily OFF-time while awake of at least 1 hour, including the early morning pre-first dose OFF (i.e. the time between wake-up and response to the first L DOPA/DDCI dosage), despite optimal anti-PD therapy (based on Investigator's assessment).
8. Experiencing wearing-off phenomenon for at least 4 weeks but less than 2 years prior to screening.
9. For females: Postmenopausal for at least 2 years before screening, surgically sterile for at least 6 months before screening, or practicing effective contraception until the post-study visit. Female patients who request to continue with oral contraceptives must be willing to use non-hormonal methods of contraception in addition during the course of this study.
10. Have filled-in self-rating diary charts in accordance with the diary chart instructions and with ≤3 errors per day while awake, in the three consecutive days preceding randomization.
11. With at least 1 hour at OFF state per day, including the early morning pre-first dose OFF period (i.e. the time between wake-up and response to the first L DOPA/DDCI dosage), as recorded in at least two of the three-day self-rating diary charts for the three days preceding randomization.
12. Adequate compliance to relevant concomitant medication during the period between V1 and V2 (based on the Investigator's judgment).

Exclusion Criteria:

1. Non-idiopathic PD (atypical parkinsonism, secondary [acquired or symptomatic] parkinsonism, Parkinson-plus syndrome).
2. Severe and/or unpredictable OFF periods, according to Investigator's judgment.
3. Average total daily OFF-time while awake of >5 hours, including the early morning pre-first dose OFF, despite optimal anti-PD therapy (based on Investigator's assessment).
4. Treatment with prohibited medication: entacapone, tolcapone, monoamine oxidase (MAO) inhibitors (except selegiline up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation, rasagiline up to 1 mg/day or safinamide up to 100 mg/day), apomorphine or antiemetics with antidopaminergic action (except domperidone) within the last 4 weeks before screening.
5. Previous or planned (during the entire study duration) deep brain stimulation or stereotactic surgery (e.g. pallidotomy, thalamotomy).
6. Previous or current use of opicapone or L-DOPA/carbidopa intestinal gel infusion.
7. Use of any other investigational product (IP), currently or within the 3 months (or within 5 half-lives of the IP, whichever is longer) before screening.
8. Past (within the past year) or present history of suicidal ideation or suicide attempts.
9. Current or previous (within the past year) alcohol or substance abuse excluding caffeine or nicotine.
10. Phaeochromocytoma, paraganglioma, or other catecholamine secreting neoplasms.
11. Known hypersensitivity to the excipients of IP (including lactose intolerance, galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption).
12. History of neuroleptic malignant syndrome or non-traumatic rhabdomyolysis.
13. History of severe hepatic impairment (Child-Pugh Class C).
14. Current or previous (within the past year) diagnosis of psychosis, severe major depression or other psychiatric disorders that, based on the Investigator's judgment, might place the patient at increased risk or interfere with assessments.
15. Any medical condition that might place the patient at increased risk or interfere with assessments.
16. For females: Pregnant or breastfeeding.
17. Employees of the Investigator, study centre, Sponsor, clinical research organisation and study consultants, when employees are directly involved in this study or other studies under the direction of this Investigator or study centre, and their family members.
18. Persons committed to an institution by virtue of an order issued either by the judicial or other authorities.
19. With an average total daily OFF-time while awake of >5 hours, including the early morning pre-first dose OFF period (i.e. the time between wake-up and response to the first L DOPA/DDCI dosage), as recorded in at least two of the three-day self-rating diary charts for the three days preceding randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 50 mg opicapone once-daily	Drug: Opicapone; 50 mg hard capsules. Oral administration, once-daily at bedtime, at least 1 hour before or after L-DOPA/carbidopa or benserazide (L-DOPA/DDCI).; Other Names: BIA 9-1067
Experimental: 100 mg of L-DOPA	Drug: L-DOPA/DDCI; L-DOPA/carbidopa or benserazide (L-DOPA/DDCI), 100/25 mg, oral administration; Other Names: Levodopa

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Absolute OFF-time from baseline to end of study	OFF = Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.	up to 7 weeks
Proportion of patients with one hour or more reduction in Absolute OFF-time from baseline to end of study (OFF-time responders)	OFF = Time when medication has worn off and is no longer providing benefit with regard to mobility, slowness, and stiffness.	up to 7 weeks
Change in Absolute ON-time from baseline to end of study	ON = Time when medication is providing benefit with regard to mobility, slowness, and stiffness.	up to 7 weeks
Proportion of patients with one hour or more increase in Absolute ON-time from baseline to end of study (ON-time responders)	ON = Time when medication is providing benefit with regard to mobility, slowness, and stiffness.	up to 7 weeks
Change in Percentage OFF-time between baseline and end of study	OFF = Time when medication has worn off and is no longer providing benefit with regard	up to 7 weeks
Change in Percentage ON-time between baseline and end of study	ON = Time when medication is providing benefit with regard to mobility, slowness, and stiffness.	up to 7 weeks

Collaborators and Investigators

• Sponsor: Bial - Portela C S.A.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Anticipated): June 30, 2023
• Study Completion (Anticipated): June 30, 2023

Study Registration Dates

• First Submitted: July 27, 2021
• First Submitted That Met QC Criteria: July 27, 2021
• First Posted (Actual): August 4, 2021

Study Record Updates

• Last Update Posted (Actual): April 13, 2023
• Last Update Submitted That Met QC Criteria: April 12, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Opicapone; Motor fluctuations; Adoption
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Catechol O-Methyltransferase Inhibitors; Levodopa; Opicapone
• Other Study ID Numbers: BIA-91067-403; 2020-002754-24 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No