Multicentre Study in Four Parallel Groups of Parkinson's Disease (PD) Patients
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: Placebo; BIA 9-1067; BIA 9-1067; BIA 9-1067; Levodopa/Carbidopa; Levodopa/Benzerazide
Intervention description: once-daily; BIA 9-1067 - 5 mg single-dose; BIA 9-1067 - 15 mg single-dose; BIA 9-1067 - 30 mg single-dose; Levodopa 100 mg Carbidopa 25 mg; Levodopa 100 mg Benzerazide 25 mg
Intervention MeSH terms: Levodopa; Carbidopa; Opicapone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 40.0
Sex: All
Minimum age: 30 Years
Healthy volunteers: No
Keywords: Parkinson Disease; BIA 9-1067

Summary:

      The purpose of this study is to investigate the tolerability and the effect of BIA 9-1067 at
      steady-state on the levodopa pharmacokinetics in Parkinson's Disease (PD) patients treated
      with levodopa/dopa-decarboxylase inhibitor.
    

Eligibility criteria:

        Inclusion Criteria:

        At screening (admission to the baseline period):

          -  Male or female of non-childbearing potential (by reason of surgery or postmenopausal);

          -  Age ≥ 30 years;

          -  A diagnosis of PD according to the UK PDS Brain Bank diagnostic criteria (bradykinesia
             and at least one of the following: muscular rigidity, rest tremor and postural
             instability);

          -  Predictable signs of end-of-dose deterioration despite "optimal" levodopa/carbidopa or
             levodopa/benserazide therapy;

          -  Modified Hoehn and Yahr stage of less than 5 in the "off" state; mean duration of
             "off" state ≥ 1.5 h during waking hours (based on historical information);

          -  Results of clinical laboratory tests acceptable by the investigator (not clinically
             significant for the well-being of the patient or for the purpose of the study);

          -  Able and willing to give written informed consent.

        At randomisation (completion of the baseline period):

          -  Been treated with a stable regimen of 3 to 8 doses per day of standard-release
             levodopa/carbidopa 100/25 mg (Sinemet®) or levodopa/benserazide 100/25 mg
             (Madopar®/Restex®) for at least 1 week prior to randomisation;

          -  Mean duration of "off" state ≥ 1.5 h during waking hours (average of recordings of
             last 3 evaluable days on patient's diary);

          -  Concomitant anti-Parkinsonian medication (other than apomorphine, entacapone or
             tolcapone) in stable doses for at least 4 weeks prior to admission.

        Exclusion Criteria:

        At screening (admission to the baseline period):

          -  Non-idiopathic parkinsonism (atypical parkinsonism, symptomatic parkinsonism,
             Parkinson-plus syndrome);

          -  Treated with entacapone, tolcapone, neuroleptics, antidepressants (except
             serotonin-specific reuptake inhibitors or imipramines [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 2 weeks prior to
             admission;

          -  Treated with any investigational product within 1 month prior to admission (or within
             5 half-lives, whichever is longer);

          -  A psychiatric or any medical condition that might place him/her at increased risk or
             interfere with assessments;

          -  Known hypersensitivity to any of the ingredients of the investigational products;

          -  A history of abuse of alcohol, drugs or medications within the last 2 years;

          -  A clinically relevant ECG abnormality;

          -  A history or current evidence of heart disease, including but not limited to
             myocardial infarction, angina, congestive heart failure and cardiac arrhythmia;

          -  Unstable concomitant disease being treated with changing doses of medication;

          -  A history or current evidence of any relevant disease in the context of this study,
             i.e., with respect to the safety of the patient (e.g., hepatic impairment) or related
             to the study conditions;

          -  A test positive for the HIV-1 or HIV-2 antibodies, or hepatitis B surface antigen
             (HbsAg), or hepatitis C antibody (HCVAb);

          -  Donated blood or received blood or blood products within the 6 months prior to
             admission;

          -  Pregnant, breast-feeding or of childbearing potential;

          -  Other condition or circumstance that, in the opinion of the investigator, may
             compromise the patient's ability to comply with the study protocol.

        At randomisation (completion of the baseline period):

          -  Treated with levodopa/DDCI in a 10:1 ratio or in a controlled-release formulation
             during the baseline period;

          -  Treated with apomorphine during the baseline period;

          -  A clinically relevant ECG abnormality.