Multicentre Study in Four Parallel Groups of Parkinson's Disease (PD) Patients

Parkinson's Disease Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01568047
• Other study ID #: BIA-91067-202
• Secondary ID: 2009-012897-12
• Status: Completed
• Phase: Phase 2
• First received: March 29, 2012
• Last updated: November 23, 2015
• Start date: February 2010
• Est. completion date: June 2010

Study information

• Verified date: November 2015
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: Ukraine: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• Placebo
once-daily
• BIA 9-1067
BIA 9-1067 - 5 mg single-dose
• BIA 9-1067
BIA 9-1067 - 15 mg single-dose
• BIA 9-1067
BIA 9-1067 - 30 mg single-dose
• Levodopa/Carbidopa
Levodopa 100 mg Carbidopa 25 mg
• Levodopa/Benzerazide
Levodopa 100 mg Benzerazide 25 mg

Locations

Country	Name	City	State
Romania	Department of Neurology C.M.D.T.A. NEOMED	Brasov
Romania	Department of Neurology-Quantum Medical Center	Bucharest
Romania	Clinica de Medicina Fizica si Recuperare Medicala-Spitalul Clinic Judetean de Urgenta Craiova	Craiova
Ukraine	Ukrainian State Scientific Research Institute of Medical and Social Problems of Disability, Department of Neurology and Adjustment Conditions	Dnipropetrovsk
Ukraine	Department No. 23 of Communal setting of medical care Kharkiv's regional clinical psychiatric hospital No. 3,	Kharkiv
Ukraine	Department of Neuroinfections and multiple sclerosis, SI "Institute of Neurology, Psychiatry and Narcology of AMS of Ukraine	Kharkiv
Ukraine	Department of Clinical Physiology and Pathology of Extrapyramidal Nervous System SI "Institute of Gerontology, AMS Ukraine"	Kyiv

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Countries where clinical trial is conducted

Romania,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax - Observed Maximum Concentration	Baseline period - to be switched respectively to standard-release levodopa/carbidopa 100/25 mg (Sinemet®) or levodopa/benserazide 100/25 mg (Madopar®/Restex®) and to adjust the number of daily doses.; Test Period - After the baseline period during the 21 to 28 days	28 days	No
Primary	Tmax - Time to Observed Maximum Concentration	Baseline period - to be switched respectively to standard-release levodopa/carbidopa 100/25 mg (Sinemet®) or levodopa/benserazide 100/25 mg (Madopar®/Restex®) and to adjust the number of daily doses.; Test Period - After the baseline period during the 21 to 28 days	28 days	No
Secondary	AUC0-6 - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to to 6 h Postdose (AUC [0-6])	Baseline period - to be switched respectively to standard-release levodopa/carbidopa 100/25 mg (Sinemet®) or levodopa/benserazide 100/25 mg (Madopar®/Restex®) and to adjust the number of daily doses.; Test Period - After the baseline period during the 21 to 28 days	28 days	No