Clinical trial NCT01568047: Multicentre Study in Four Parallel Groups of Parkinson's Disease (PD) Patients
Official title: Multicentre, Double-blind, Randomised, Placebo-controlled Study in Four Parallel Groups of PD Patients Treated With Standard-release Levodopa/Carbidopa 100/25 mg (Sinemet®) or Levodopa/Benserazide 100/25 mg (Madopar®/Restex®) and With Motor Fluctuations ("Wearing-off" Phenomenon)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Parkinson Disease
BIA 9-1067
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2012-04-02
Enrollment: 40
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Multicentre, double-blind, randomised, placebo-controlled study in four parallel groups of PD patients treated with standard-release levodopa/carbidopa 100/25 mg (Sinemet®) or levodopa/benserazide 100/25 mg (Madopar®/Restex®) and with motor fluctuations ("wearing-off" phenomenon)

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.

Primary outcomes:
measure: Cmax - Observed Maximum Concentration
timeFrame: 28 days
measure: Tmax - Time to Observed Maximum Concentration
timeFrame: 28 days
Secondary outcomes:
measure: AUC0-6 - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to to 6 h Postdose (AUC [0-6])
timeFrame: 28 days
Other outcomes:
Locations:
city: Brasov
country: Romania
facility: Department of Neurology C.M.D.T.A. NEOMED
city: Bucharest
country: Romania
facility: Department of Neurology-Quantum Medical Center
city: Craiova
country: Romania
facility: Clinica de Medicina Fizica si Recuperare Medicala-Spitalul Clinic Judetean de Urgenta Craiova
city: Dnipropetrovsk
country: Ukraine
facility: Ukrainian State Scientific Research Institute of Medical and Social Problems of Disability, Department of Neurology and Adjustment Conditions
city: Kharkiv
country: Ukraine
facility: Department No. 23 of Communal setting of medical care Kharkiv's regional clinical psychiatric hospital No. 3,
city: Kharkiv
country: Ukraine
facility: Department of Neuroinfections and multiple sclerosis, SI "Institute of Neurology, Psychiatry and Narcology of AMS of Ukraine
city: Kyiv
country: Ukraine
facility: Department of Clinical Physiology and Pathology of Extrapyramidal Nervous System SI "Institute of Gerontology, AMS Ukraine"
Study officials:
References: