A Study to Investigate the Tolerability and Effect of Three Single-dose Regimens of BIA 9-1067
A Study to Investigate the Tolerability and Effect of Three Single-dose Regimens of BIA 9-1067
The purpose of this study is to investigate the effect of BIA 9-1067 on the levodopa
 pharmacokinetics when administered in combination with immediate release levodopa/carbidopa
 or levodopa/benserazide in Parkinson's Disease (PD) patients.
This was a three-centre, double-blind, randomised, placebo-controlled, crossover study with
 four consecutive single-dose treatment periods in PD patients treated with immediate release
 100 mg/25 mg levodopa/carbidopa or 100 mg/25 mg levodopa/benserazide
Inclusion Criteria:

 -  Male or female of non-childbearing potential (by reason of surgery or postmenopausal);

 -  Aged between 30 and 75 years, inclusive;

 -  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;

 -  Been treated with a stable regimen of 3 to 8 doses of standard release 100 mg/25 mg
 levodopa/carbidopa or 100 mg/25 mg levodopa/benserazide per day within at least 1 week
 prior to randomisation;

 -  Modified Hoehn and Yahr stage of less than 5 in the off-state;

 -  Mean duration of OFF stage ≥ 1.5 h during waking hours (based on historical
 information);

 -  Concomitant anti-Parkinsonian medication (other than apomorphine, entacapone or
 tolcapone) in stable doses for at least 4 weeks prior to randomisation;

 -  Results of clinical laboratory tests acceptable by the investigator (not clinically
 significant for the well-being of the subject or for the purpose of the study);

 -  Able and willing to give written informed consent.

 Exclusion Criteria:

 -  Non-idiopathic parkinsonism (atypical parkinsonism, symptomatic parkinsonism,
 Parkinson-plus syndrome);

 -  Treated with levodopa/carbidopa or levodopa/benserazide in a 10:1 ratio, or with
 levodopa/carbidopa in a controlled-release formulation;

 -  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 4 weeks prior to
 randomisation;

 -  Treated with apomorphine within 7 days prior to randomisation;

 -  Treated with any investigational product within 2 months prior to randomisation (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 subject (e.g., hepatic or renal impairment) or
 related to the study conditions;

 -  A test positive for the human immunodeficiency viruses (HIV) 1 or 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
 randomisation;

 -  Pregnant, breast-feeding or of childbearing potential;

 -  Other condition or circumstance that, in the opinion of the investigator, may
 compromise the subject's ability to comply with the study protocol.