A Study to Investigate the Tolerability and Effect of Three Single-dose Regimens of BIA 9-1067

Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01568034
• Other study ID #: BIA-91067-201
• Secondary ID: 2008-003869-72
• Status: Completed
• Phase: Phase 2
• First received: March 29, 2012
• Last updated: December 19, 2014
• Start date: April 2009
• Est. completion date: February 2010

Study information

• Verified date: December 2014
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Portugal: National Pharmacy and Medicines Institute
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• BIA 9-1067
BIA 9-1067 - 25 mg single-dose
• BIA 9-1067
BIA 9-1067 - 50 mg single-dose
• BIA 9-1067
BIA 9-1067 - 100 mg single-dose
• Placebo
single-dose
• Levodopa/Carbidopa
Levodopa 100 mg Carbidopa 25 mg
• Levodopa/Benzerazide
Levodopa 100 mg Benzerazide 25 mg

Locations

Country	Name	City	State
Portugal	Department of Neurology-Hospital de Santa Maria-Faculty of Medicine, University of Lisbon	Lisbon
Romania	Spitalul Clinic Colentina - Clinica de Neurologie	Bucharest
Ukraine	Department of Neurology- Hospital of the department of medical care of Ministry Internal Affairs of Ukraine	Kyiv

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Countries where clinical trial is conducted

Portugal,  Romania,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax - Maximum Plasma Concentration Day 3	Cmax - Maximum plasma concentration (ng/mL)	Day 3	No
Primary	Tmax = Time to Cmax Day 3	tmax = time to Cmax (values are median)	Day 3	No
Secondary	AUC0-6 - Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours Post-dose (Day 3)	AUC0-6 - area under the plasma concentration-time curve from time 0 to 6 hours post-dose (ng.h/mL)	Day 3	No