Clinical study in early PD patients to investigate the effect of Opicapone 50mg or Levodopa 100 mg in the treatment of motor fluctuations.

• Register: EUCTR
• Last refreshed on: 28 October 2024
• Main ID: EUCTR2020-002754-24-IT
• Date of registration: 30/08/2021
• Prospective Registration: Yes
• Primary sponsor: BIAL-Portela & Ca, S.A.
• Public title: Clinical study in early PD patients to investigate the effect of Opicapone 50mg or Levodopa 100 mg in the treatment of motor fluctuations.
• Scientific 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. - ADOPTION: eArly levoDopa with Opicapone in Parkinson's paTients wIth motOr fluctuatioNs
• Date of first enrolment: 09/09/2021
• Target sample size: 100
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-002754-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Germany, Italy, Portugal, Spain, United Kingdom

Contacts

• Name: Raquel Costa, PharmD
• Affiliation: Bial - Portela & Ca, S.A.

• Name: Raquel Costa, PharmD
• Affiliation: Bial - Portela & Ca, S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion criteria at screening (V1)
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 nonhormonal methods of contraception in addition during the course of this study.

Inclusion criteria at baseline (V2)
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).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 60

Exclusion criteria:
Exclusion criteria at screening (V1)
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 glucosegalactose 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.
Exclusion criteria at baseline (V2)
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Parkinson's Disease (PD)
MedDRA version: 20.0 Level: HLT Classification code 10034005 Term: Parkinson's disease and parkinsonism System Organ Class: 100000004852

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: SINEMET 100 mg + 25 mg tablets
Product Name: SINEMET 100 mg + 25 mg compresse
Product Code: [023145028]
Pharmaceutical Form: Tablet
INN or Proposed INN: Levodopa
Current Sponsor code: Not available
Other descriptive name: Levodopa
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: Carbidopa
Current Sponsor code: Not available
Other descriptive name: Carbidopa
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Madopar 125 mg T, tablets
Product Name: Madopar® 125 mg T Tablets Levodopa 100 mg Benserazide 25 mg (as benserazide hydrochloride)
Product Code: [6036937.00.01]
Pharmaceutical Form: Tablet
INN or Proposed INN: BENSERAZIDE HYDROCHLORIDE
CAS Number: 14919-77-8
Current Sponsor code: Not available
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
INN or Proposed INN: Levodopa
Current Sponsor code: Not available
Other descriptive name: Levodopa
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Ongentys 50 mg hard capsules
Product Name: Ongentys 50 mg capsule rigide
Product Code: [BIA 9-1067]
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Opicapone
CAS Number: 923287-50-7
Current Sponsor code: Not Available
Other descriptive name: Opicapone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: From baseline to end of study

Main Objective: To evaluate the add-on efficacy of opicapone 50 mg or an extra dose of L-DOPA 100 mg as first strategy for the treatment of wearing-off in patients with PD.

Primary end point(s): Change in Absolute OFF-time from baseline to end of study

Secondary Objective: To investigate the safety and tolerability of combined treatment (current L-DOPA/DDCI treatment plus opicapone 50 mg or an extra dose of 100 mg of L-DOPA) for treatment of wearing-off in PD patients.

Secondary Outcome(s)

Secondary end point(s): Efficacy assessments
• Change in Absolute OFF-time from baseline to end of study
• Proportion of patients with one hour or more reduction in Absolute OFF-time from baseline to end of study (OFF-time responders)
• Change in Absolute ON-time from baseline to end of study
• Proportion of patients with one hour or more increase in Absolute ON-time from baseline to end of study (ON-time responders)
• Change in Percentage OFF-time between baseline and end of study (calculated as the sum in minutes from 30-minute periods classified as OFF divided by the total time awake)
• Change in Percentage ON-time between baseline and end of study (calculated as the sum in minutes from 30-minute periods classified as ON divided by the total time awake)
• Additional efficacy outcomes include the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), the Movement Disorder Society- Non-Motor Rating Scale (MDS-NMS), the Parkinson’s Disease Questionnaire-8 (PDQ-
8), the Clinical Global Impression of Improvement (CGI-I) and the Patient Global Impression of Change (PGI-C)
Safety assessments
• Adverse Events (AEs) and Serious Adverse Events (SAEs) collected from screening to the post-study follow-up visit

Timepoint(s) of evaluation of this end point: From baseline to end of study

Secondary ID(s)

2020-002754-24-ES

NCT03959540

BIA-91067-403

Source(s) of Monetary Support

Bial - Portela & Ca, S.A.

Ethics review

Status: Approved
Approval date: 09/09/2021
Contact: