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

Parkinson Disease Clinical Trial

— ADOPTION  

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04990284
• Other study ID #: BIA-91067-403
• Secondary ID: 2020-002754-24
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: November 29, 2021
• Est. completion date: June 30, 2023

Study information

• Verified date: April 2023
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 106
• Est. completion date: June 30, 2023
• Est. primary completion date: June 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

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).
• L-DOPA/DDCI
L-DOPA/carbidopa or benserazide (L-DOPA/DDCI), 100/25 mg, oral administration

Locations

Country	Name	City	State
Germany	Charite Universitaetsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Praxis Dr. med. Kirsten Hahn	Berlin
Germany	Universitaetsklinikum Freiburg	Freiburg	Baden Wuerttemberg
Germany	Praxis Dr. Oehlwein	Gera	Thueringen
Germany	Klinik Haag i. OB	Haag in Oberbayern	Bayern
Germany	Asklepios Fachklinikum Stadtroda	Stadtroda	Thueringen
Germany	Parkinson-Klinik Ortenau GmbH&Co KG	Wolfach	Baden Wuerttemberg
Germany	Universitaetsklinikum Wuerzburg	Wuerzburg	Bayern
Italy	Fondazione IRCCS CA' Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Universitaria- Università degli Studi della Campania "Luigi Vanvitelli"	Napoli
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Azienda Ospedaliera Santa Maria di Terni	Terni
Portugal	Hospital Beatriz Ângelo	Loures	Lisboa
Portugal	CNS-Campus Neurologico Senior	Torres Vedras	Lisboa
Spain	Complejo Hospitalario Universitario A Coruña	A Coruña	La Coruña
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Hospital Ruber Internacional	Madrid
Spain	Hospital Universitario Puerta de Hierro Majadahonda	Majadahonda	Madrid
Spain	Complejo Hospitalario Universitario de Orense	Ourense
Spain	Hospital de Sant Joan Despi Moises Broggi	Sant Joan Despí	Barcelona
United Kingdom	Royal Devon and Exeter Hospital (Wonford)	Exeter	Devon
United Kingdom	King's College Hospital	London	Greater London
United Kingdom	Newcastle University- Clinical Ageing Research Unit	Newcastle Upon Tyne	Tyne & Wear
United Kingdom	University Hospitals Plymouth	Plymouth	Devon

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Countries where clinical trial is conducted

Germany,  Italy,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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