Clinical trial NCT03103399 (phase 2, status: completed)
Conditions: parkinson disease
ICD codes: G20
Drugs: comtan®, nebicapone, levodopa/ddci, placebo
SMILES: CCN(CC)C(=O)C(=C\C1=CC(=C(O)C(O)=C1)[N+]([O-])=O)\C#N, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Eligibility criteria:

        Inclusion Criteria:

        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

          -  Average of at least 1.5 "off" hours per day (excluding the early morning pre first
             dose "off" period) on the 3 day diaries, filled in on the 3 days preceding Visit V3,
             according to the self-rating diary charts completed during Period 1

        Exclusion Criteria:

        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

          -  History or current evidence of any relevant disease in the context of this study, i.e.
             with respect to the safety of the patient or related to the study conditions, e.g.
             that may influence the absorption or metabolism (e.g. hepatic impairment) of the
             investigational drug

          -  Any abnormality in the liver enzymes above 2 times the upper limit of the normal range