Efficacy and Tolerability of Nebicapone in Parkinson's Disease Patients With "Wearingoff" Phenomenon

NCT03103399 | Completed Phase 2

• 1 other identifier: BIA-3202-202
• Study Type: interventional
• Target: 254
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study was to investigate the effect on the "wearing-off" phenomenon of 3 different doses of nebicapone (NEB 50 mg, 100 mg and 150 mg), compared with entacapone and placebo when dministered concomitantly with existing treatment with levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide).

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Change from baseline in absolute "off" time (time with poor mobility or complete immobility) at Visit V7

  Baseline values for all efficacy variables were the values from Visit V3, and change from baseline refers to absolute change from baseline at Visit 7 (end of the 8-week treatment period)

  8 weeks

Secondary Outcomes (2)

• Proportion of "off" time responders

  8 weeks

• Proportion of "on" time responders

  8 weeks

Study Arms (5)

50 mg nebicapone

EXPERIMENTAL

At Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 50 mg of the study treatment in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2)

Drug: Nebicapone; Drug: Levodopa/DDCI; Drug: Placebo

100 mg nebicapone

EXPERIMENTAL

At Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 100 mg of the study treatment in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2)

Drug: Nebicapone; Drug: Levodopa/DDCI; Drug: Placebo

150 mg nebicapone

EXPERIMENTAL

At Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 150 mg of the study treatment in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2)

Drug: Nebicapone; Drug: Levodopa/DDCI; Drug: Placebo

200 mg entacapone

ACTIVE COMPARATOR

At Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive 200 mg of entacapone (Comtan®) in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2)

Drug: Comtan®; Drug: Levodopa/DDCI; Drug: Placebo

Placebo

PLACEBO COMPARATOR

At Visit V2, patients received a supply of a placebo to take concomitantly with each levodopa/DDCI dose for the duration of the run-in period (Period 1). At the end of Period 1, patients were randomised to receive study treatment matching placebo tablets in addition to their levodopa/DDCI therapy for the duration of the double-blind (Period 2)

Drug: Levodopa/DDCI; Drug: Placebo

Interventions

Comtan® DRUG

200 mg entacapone were to be taken concomitantly with each levodopa/DDCI dose.

Also known as: entacapone

200 mg entacapone

Nebicapone DRUG

50 mg, 100 mg and 150 mg doses of nebicapone were to be taken concomitantly with each levodopa/DDCI dose.

Also known as: BIA 3-202

100 mg nebicapone; 150 mg nebicapone; 50 mg nebicapone

Levodopa/DDCI DRUG

Prior to the study, all patients were to have been receiving levodopa/DDCI therapy for at least 1 year with clear clinical improvement. At entry to the study, patients were to be receiving levodopa/DDCI therapy of at least 4 but not more than 8 (inclusive) standard daily doses. All patients were to continue receiving levodopa/DDCI during the study. Levodopa and DDCI were prescribed by the investigators and purchased locally by patients.

Also known as: Levodopa plus a dopa decarboxylase inhibitor (DDCI: carbidopa or benserazide)

100 mg nebicapone; 150 mg nebicapone; 200 mg entacapone; 50 mg nebicapone; Placebo

Placebo DRUG

Administered orally as encapsulated tablets, which were identical in appearance to the study drugs

Also known as: placebo tablets

100 mg nebicapone; 150 mg nebicapone; 200 mg entacapone; 50 mg nebicapone; Placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At Visit V1 (screening), patients had to be/have:
• Ability to comprehend and willingness to sign an informed consent form
• Aged 30 to 80 years, inclusive
• Diagnosis of idiopathic Parkinson's disease according to the Brain Bank Clinical Diagnosis Criteria of the UK Parkinson's Disease Society \[Hughes et al, 1992\]
• Disease severity less than Stage 5 (modified Hoehn \& Yahr staging) while during the "off" time
• Treated with levodopa plus DDCI for at least 1 year with clear clinical improvement
• Treated with 4 to 8 (inclusive) daily doses of standard levodopa plus DDCI (bedtime dose of a slow-release formulation is permitted)
• Stable regimen of levodopa plus DDCI and other anti Parkinson drugs for at least 4 weeks before screening
• Signs of end-of-dose "wearing-off" phenomenon (end-of-dose deterioration) with average total daily "off" time while awake of at least 1.5 hours excluding the early morning pre first dose "off" period despite optimal anti Parkinson therapy, determined subjectively and objectively (observations of the investigator) for a minimum of 2 months before screening
• Ability to keep reliable diaries of motor fluctuations (alone or with family/caregiver assistance)
• Patient must be amenorrhoeic for at least 1 year or surgically sterile for at least 6 months before screening. In case of women of childbearing potential, patient must be using double-barrier contraceptive method.
• At Visit V2 (entry to Period 1), patients had to have the results of laboratory tests acceptable by the investigator (not clinically relevant for the well being of the patient or for the purpose of the study).
• At Visit V3 (randomisation), patients had to have:
• At least 80% treatment medication (levodopa/DDCI plus investigational product) compliance with the recommended dosage regimen during Period 1
• Self-rating diary charts filled in in accordance with the diary chart instructions; less than 3 errors per day are allowed

You may not qualify if:

• At Visit V1 (screening), patients were not to be/have:
• Non-idiopathic Parkinson's disease (atypical parkinsonism, symptomatic parkinsonism, Parkinson-plus syndrome)
• Dyskinesia disability score more than 3 in the Unified Parkinson's Disease Rating Scale (UPDRS) IV.A item 33
• Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criterion for dementia
• Major depressive episode within the 6 months before screening
• Treatment with entacapone, tolcapone, neuroleptics, antidepressants (except serotonin-specific reuptake inhibitors or imipraminics \[desipramine, imipramine, clomipramine and amitriptyline\]), monoamine oxidase inhibitors (except selegiline up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation or rasagiline up to 1 mg/day), or antiemetics (except domperidone) within the 3 months before screening
• Treatment with apomorphine within the previous month before screening
• Dosage change of concomitant anti Parkinson medication within 4 weeks of screening
• Any investigational product within the 3 months (or within 5 half-lives, whichever is longer) before screening
• A psychiatric or any medical condition that might place the patient at increased risk or interfere with assessment
• A clinically relevant electrocardiogram (ECG) abnormality
• A history or current evidence of heart disease, including but not limited to myocardial infarction, angina, congestive heart failure and cardiac arrhythmia
• Phaeochromocytoma
• Known hypersensitivity to the ingredients of products used
• Unstable concomitant disease being treated with changing doses of medication

Sponsors & Collaborators

• Bial - Portela C S.A.: lead

MeSH Terms

Conditions

Parkinson Disease

Interventions

entacapone; nebicapone; Levodopa; Benserazide

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine; Hydrazines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2017
• First Posted: April 6, 2017
• Study Start: September 26, 2006
• Primary Completion: September 21, 2007
• Study Completion: September 21, 2007
• Last Updated: April 6, 2017

Record last verified: 2017-03