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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bial - Portela C S.A.
ClinicalTrials.gov Identifier:
NCT01568047
First received: March 29, 2012
Last updated: November 23, 2015
Last verified: November 2015
  Purpose
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.

Condition Intervention Phase
Parkinson's Disease
Drug: Placebo
Drug: BIA 9-1067
Drug: Levodopa/Carbidopa
Drug: Levodopa/Benzerazide
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Bial - Portela C S.A.:

Primary Outcome Measures:
  • Cmax - Observed Maximum Concentration [ Time Frame: 28 days ] [ Designated as safety issue: No ]

    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


  • Tmax - Time to Observed Maximum Concentration [ Time Frame: 28 days ] [ Designated as safety issue: No ]

    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



Secondary Outcome Measures:
  • AUC0-6 - Area Under the Plasma Concentration-time Curve (AUC) From Time Zero to to 6 h Postdose (AUC [0-6]) [ Time Frame: 28 days ] [ Designated as safety issue: No ]

    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



Enrollment: 40
Study Start Date: February 2010
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo

PLC, Placebo

Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half

Drug: Placebo
once-daily
Other Name: PLC
Drug: Levodopa/Carbidopa
Levodopa 100 mg Carbidopa 25 mg
Other Name: Sinemet
Drug: Levodopa/Benzerazide
Levodopa 100 mg Benzerazide 25 mg
Other Name: Madopar®/Restex®
Experimental: BIA 9-1067 - 5 mg

5 mg BIA 9-1067 (OPC, Opicapone)

Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half

Drug: BIA 9-1067
BIA 9-1067 - 5 mg single-dose
Other Name: OPC, Opicapone
Drug: Levodopa/Carbidopa
Levodopa 100 mg Carbidopa 25 mg
Other Name: Sinemet
Drug: Levodopa/Benzerazide
Levodopa 100 mg Benzerazide 25 mg
Other Name: Madopar®/Restex®
Experimental: BIA 9-1067 - 15 mg

15 mg BIA 9-1067 (OPC, Opicapone)

Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half

Drug: BIA 9-1067
BIA 9-1067 - 15 mg single-dose
Other Name: OPC, Opicapone
Drug: Levodopa/Carbidopa
Levodopa 100 mg Carbidopa 25 mg
Other Name: Sinemet
Drug: Levodopa/Benzerazide
Levodopa 100 mg Benzerazide 25 mg
Other Name: Madopar®/Restex®
Experimental: BIA 9-1067 - 30 mg

30 mg BIA 9-1067 (OPC, Opicapone)

Levodopa/Carbidopa combination were given to half of the volunteers and Levodopa/Benzerazide to the other half

Drug: BIA 9-1067
BIA 9-1067 - 30 mg single-dose
Other Name: OPC, Opicapone
Drug: Levodopa/Carbidopa
Levodopa 100 mg Carbidopa 25 mg
Other Name: Sinemet
Drug: Levodopa/Benzerazide
Levodopa 100 mg Benzerazide 25 mg
Other Name: Madopar®/Restex®

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

Ages Eligible for Study:   30 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01568047

Locations
Romania
Department of Neurology C.M.D.T.A. NEOMED
Brasov, Romania, 500 283
Department of Neurology-Quantum Medical Center
Bucharest, Romania, 024 092
Clinica de Medicina Fizica si Recuperare Medicala-Spitalul Clinic Judetean de Urgenta Craiova
Craiova, Romania, 200 642
Ukraine
Ukrainian State Scientific Research Institute of Medical and Social Problems of Disability, Department of Neurology and Adjustment Conditions
Dnipropetrovsk, Ukraine, 49027
Department No. 23 of Communal setting of medical care Kharkiv's regional clinical psychiatric hospital No. 3,
Kharkiv, Ukraine, 61068
Department of Neuroinfections and multiple sclerosis, SI "Institute of Neurology, Psychiatry and Narcology of AMS of Ukraine
Kharkiv, Ukraine, 61068
Department of Clinical Physiology and Pathology of Extrapyramidal Nervous System SI "Institute of Gerontology, AMS Ukraine"
Kyiv, Ukraine, 04114
Sponsors and Collaborators
Bial - Portela C S.A.
  More Information

Responsible Party: Bial - Portela C S.A.
ClinicalTrials.gov Identifier: NCT01568047     History of Changes
Other Study ID Numbers: BIA-91067-202  2009-012897-12 
Study First Received: March 29, 2012
Results First Received: February 5, 2014
Last Updated: November 23, 2015
Health Authority: Ukraine: Ministry of Health

Keywords provided by Bial - Portela C S.A.:
Parkinson Disease
BIA 9-1067

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Levodopa
Carbidopa
Opicapone
Carbidopa, levodopa drug combination
Benserazide, levodopa drug combination
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Aromatic Amino Acid Decarboxylase Inhibitors
Enzyme Inhibitors
Catechol O-Methyltransferase Inhibitors
Adjuvants, Immunologic
Immunologic Factors
Dopamine Agonists

ClinicalTrials.gov processed this record on August 28, 2016