Clinical trial NCT01568034: A Study to Investigate the Tolerability and Effect of Three Single-dose Regimens of BIA 9-1067
Official title: A Double-blind, Randomised, Placebo-controlled, Cross-over Study to Investigate the Tolerability and Effect of Three Single-dose Regimens of BIA 9-1067 on the Levodopa Pharmacokinetics, Motor Response, and Erythrocyte Soluble Catechol-O-methyltransferase Activity in Parkinson's Disease Patients Concomitantly Treated With Levodopa/Dopa-decarboxylase Inhibitor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Parkinson's Disease
BIA 9-1067
Lead sponsor: Bial - Portela C S.A.
Sponsor class: INDUSTRY
First posted: 2012-04-02
Enrollment: 10
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax - Maximum Plasma Concentration Day 3
timeFrame: Day 3
measure: Tmax = Time to Cmax Day 3
timeFrame: Day 3
Secondary outcomes:
measure: AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3)
timeFrame: Day 3
Other outcomes:
Locations:
city: Lisbon
country: Portugal
facility: Department of Neurology-Hospital de Santa Maria-Faculty of Medicine, University of Lisbon
city: Bucharest
country: Romania
facility: Spitalul Clinic Colentina - Clinica de Neurologie
city: Kyiv
country: Ukraine
facility: Department of Neurology- Hospital of the department of medical care of Ministry Internal Affairs of Ukraine
Study officials:
affiliation: Hospital de Santa Maria, Lisbon
name: Joaquim Ferreira, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: