Clinical trial NCT04990284: eArly levoDopa With Opicapone in Parkinson's paTients wIth motOr fluctuatioNs.
Official 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson Disease
Keywords: Adoption
Opicapone
Motor fluctuations
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2021-08-04
Enrollment: 106
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Change in Absolute OFF-time from baseline to end of study
timeFrame: up to 7 weeks
measure: Proportion of patients with one hour or more reduction in Absolute OFF-time from baseline to end of study (OFF-time responders)
timeFrame: up to 7 weeks
measure: Change in Absolute ON-time from baseline to end of study
timeFrame: up to 7 weeks
measure: Proportion of patients with one hour or more increase in Absolute ON-time from baseline to end of study (ON-time responders)
timeFrame: up to 7 weeks
measure: Change in Percentage OFF-time between baseline and end of study
timeFrame: up to 7 weeks
measure: Change in Percentage ON-time between baseline and end of study
timeFrame: up to 7 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
state: Baden Wuerttemberg
city: Wolfach
country: Germany
facility: Parkinson-Klinik Ortenau GmbH&Co KG
state: Baden Wuerttemberg
city: Haag in Oberbayern
country: Germany
facility: Klinik Haag i. OB
state: Bayern
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
state: Bayern
city: Gera
country: Germany
facility: Praxis Dr. Oehlwein
state: Thueringen
city: Stadtroda
country: Germany
facility: Asklepios Fachklinikum Stadtroda
state: Thueringen
city: Berlin
country: Germany
facility: Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Praxis Dr. med. Kirsten Hahn
city: Milano
country: Italy
facility: Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Terni
country: Italy
facility: Azienda Ospedaliera Santa Maria di Terni
city: Loures
country: Portugal
facility: Hospital Beatriz Ângelo
state: Lisboa
city: Torres Vedras
country: Portugal
facility: CNS-Campus Neurologico Senior
state: Lisboa
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Sant Joan Despí
country: Spain
facility: Hospital de Sant Joan Despi Moises Broggi
state: Barcelona
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
state: La Coruña
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
city: Ourense
country: Spain
facility: Complejo Hospitalario Universitario de Orense
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital (Wonford)
state: Devon
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth
state: Devon
city: London
country: United Kingdom
facility: King's College Hospital
state: Greater London
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle University- Clinical Ageing Research Unit
state: Tyne & Wear
Study officials:
References: