Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson's Disease Patients With "Wearing-off" Phenomenon

Sponsor
Bial - Portela C S.A. (Industry)
Overall Status
Completed
CT.gov ID
NCT01568073
Collaborator
(none)
600
1
3
32.1
18.7

Study Details

Study Description

Brief Summary

This study aims to demonstrate the efficacy and safety of BIA 9-1067, compared with entacapone or placebo, when administered with the existing treatment of L-DOPA plus a Dopa Decarboxylase Inhibitor (DDCI), in patients with Parkinson's Disease (PD) and end-of-dose motor fluctuations.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Efficacy and safety of BIA 9-1067 in idiopathic Parkinson's disease patients with "wearing-off" phenomenon treated with levodopa plus a dopa decarboxylase inhibitor (DDCI): a double-blind, randomised, placebo- and active-controlled, parallel-group, multicentre clinical study.

Study Design

Study Type:
Interventional
Actual Enrollment :
600 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson's Disease Patients With "Wearing-off" Phenomenon Treated With Levodopa Plus a Dopa Decarboxylase Inhibitor (DDCI): a Double-blind, Randomised, Placebo- and Active-controlled, Parallel-group, Multicentre Clinical Study
Study Start Date :
Mar 1, 2011
Actual Primary Completion Date :
Nov 1, 2013
Actual Study Completion Date :
Nov 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: BIA 9-1067

OPC, Opicapone

Drug: BIA 9-1067
5, 25 and 50 mg of BIA 9-1067 (once-daily)
Other Names:
  • OPC, Opicapone
  • Drug: Levodopa
    Other Names:
  • L-Dopa
  • Drug: Carbidopa
    DOPA decarboxylase inhibitor

    Drug: Benserazide
    DOPA decarboxylase inhibitor

    Active Comparator: Entacapone

    Comtan®; Active comparator

    Drug: Entacapone
    200 mg entacapone (concomitantly with each L-dopa/DDCI dose)
    Other Names:
  • Comtan®
  • Drug: Levodopa
    Other Names:
  • L-Dopa
  • Drug: Carbidopa
    DOPA decarboxylase inhibitor

    Drug: Benserazide
    DOPA decarboxylase inhibitor

    Placebo Comparator: Placebo

    PLC, Placebo

    Drug: Placebo
    200 mg
    Other Names:
  • PLC
  • Drug: Levodopa
    Other Names:
  • L-Dopa
  • Drug: Carbidopa
    DOPA decarboxylase inhibitor

    Drug: Benserazide
    DOPA decarboxylase inhibitor

    Outcome Measures

    Primary Outcome Measures

    1. Efficacy of 3 BIA 9-1067 (5 mg, 25 mg, and 50 mg) Compared With 200 mg of Entacapone or Placebo, [14 to 15 weeks]

      The primary efficacy variable will be the change from baseline in absolute OFF-time at the end of the DB period, This results refers when administered with the existing treatment of L-DOPA plus a DDCI, in patients with PD and end-of-dose motor fluctuations

    Secondary Outcome Measures

    1. Total UPDRS SCORE (I, II (ON), and III) [14 to 15 weeks]

      Total UPDRS (Part I, II (ON) and III) UPDRS I evaluation of mentation, behavior, and mood UPDRS II self-evaluation of the activities of daily life (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food UPDRS III clinician-scored monitored motor evaluation The UPDRS I, II and III scores and subscores are calculated as the sum of all individual items. If one or two items in a scale are missing, they will be imputed with the mean of the non-missing items of that scale. Subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe The final cumulative score will range from 0 (no disability) to 199 (total disability).

    2. Parkinson's Disease Sleep Scale (PDSS) [14 to 15 weeks]

      The Parkinson's disease Sleep Scale (PDSS) is a specific scale for the assessment of sleep disturbances in subjects with PD. The PDSS score is calculated as the sum of all single items. If one or two items are missing, they will be imputed with the mean of the non-missing items. If three or more items are missing, no imputation will be done and the score will be set to missing. Subscale has 0-10 ratings, where 0 = severe and 10 = normal The PDSS total score is a sum score of all 15 questions and ranges from 0 to 150, with lower scores meaning more disability.

    3. Non-motor Symptoms Scale (NMSS) [14 to 15 weeks]

      The Non-motor Symptoms Scale (NMSS) consists of 30 questions, covering 9 dimensions, whereby each item is scored for severity and frequency: Severity None 0 Mild (symptoms present but causes little distress) 1 Moderate (some distress or disturbance to subject) 2 Severe (major source of distress or disturbance to subject) 3 Frequency Rarely (<1/wk) 1 Often (1/wk) 2 Frequent (several times per week) 3 Very Frequent (daily or all the time) 4 The product of frequency and severity is calculated for each item and each dimension score is defined as the sum of the frequency*severity of the respective items. If frequency or severity of a single item is missing, the domain score will not be calculated. The NMSS total score is defined as the sum of all domain scores. The NMSS total score is calculated by adding all domain scores (0-360), and lower scores mean less disability.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    30 Years to 83 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    V1 (Screening, up to 14 days before V2)

    • Able to comprehend and willing to sign an informed consent form.

    • Male and female subjects between 30 and 83 years old, inclusive.

    • Diagnosed with idiopathic PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria for at least 3 years.

    • Disease severity Stages I-III (modified Hoehn &Yahr staging) at ON.

    • Treated with L-DOPA/DDCI for at least 1 year with clear clinical improvement as per investigator's judgment.

    • Treated with 3 to 8 daily doses of L-DOPA/DDCI, which can include a slow-release formulation.

    • On a stable regimen of L-DOPA/DDCI and other anti-PD drugs for at least 4 weeks before screening.

    • Signs of "wearing-off" phenomenon (end-of-dose deterioration) for a minimum of 4 weeks before screening, with average total daily OFF time while awake of at least 1.5 hours, excluding the early morning pre-first dose OFF, despite optimal anti-PD therapy (based on the investigator's judgment).

    • Able to keep reliable diaries of motor fluctuations (alone or with family/caregiver assistance).

    • Amenorrheic for at least 1 year or surgically sterile for at least 6 months before screening. Females of childbearing potential must be using an effective non-hormonal contraceptive method.

    V2 (Randomisation, Day 0)

    • Have filled-in self-rating diary charts in accordance with the diary chart instructions and with ≤ 3 errors per day.

    • At least 1.5 OFF hours per day, excluding the early morning pre-first dose OFF period (i.e. the time between wake-up and response to the first L DOPA/DDCI dosage), as recorded in the self-rating diary for at least 2 of the 3 days preceding V2.

    • Results of the screening laboratory tests are considered acceptable by the investigator (i.e. not clinically relevant for the well-being of the subject or for the purpose of the study).

    Exclusion Criteria:

    V1 (Screening, up to 14 days before V2)

    • Non-idiopathic PD (atypical parkinsonism, secondary [acquired or symptomatic] parkinsonism, Parkinson-plus syndrome).

    • Dyskinesia disability score > 3 in the Unified Parkinson's Disease Rating Scale (UPDRS) Sub-section IV A, item 33.

    • Severe and/or unpredictable OFF periods.

    • Treatment with prohibited medication: tolcapone, neuroleptics, venlafaxine, 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 with antidopaminergic action (except domperidone) within the month before screening.

    • Previous use of entacapone.

    • Treatment with apomorphine, alpha-methyldopa, or reserpine within the month before screening or likely to be needed at any time during the study.

    • Dosage change of concomitant anti-PD medication within 4 weeks of screening.

    • Previous or planned (during the entire study duration, including the OL period) deep brain stimulation.

    • Previous stereotactic surgery (e.g. pallidotomy, thalamotomy) for PD or with planned stereotactic surgery during the study period.

    • Any IMP within the 3 months (or within 5 half-lives, whichever is longer) before screening.

    • Any medical condition that might place the subject at increased risk or interfere with assessments.

    • Past (within the past year) or present history of suicidal ideation or suicide attempts.

    • Current or previous (within the past year) diagnosis of major depressive disorder, mania, bipolar disorder, psychosis, dysthymia, generalised anxiety disorder, alcohol or substance abuse excluding caffeine or nicotine, impulse control disorders (e.g. pathological gambling), dementia or eating disorders according to Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV) American Psychiatric Association, 2000 criteria, as determined by the investigator.

    • A clinically relevant electrocardiogram (ECG) abnormality (relevance should be assessed by a cardiologist if needed).

    • Current evidence of unstable cardiovascular disease, including but not limited to uncontrolled hypertension, myocardial infarction with important systolic or diastolic dysfunction, unstable angina, congestive heart failure (New York Heart Association class ≥ III), and significant cardiac arrhythmia (Mobitz II 2nd or 3rd degree AV block or any other arrhythmia causing haemodynamic repercussions as symptomatic bradycardia or syncope).

    • Prior renal transplant or current renal dialysis.

    • Pheochromocytoma, paraganglioma, or other catecholamine secretive neoplasm.

    • Known hypersensitivity to the ingredients of IMPs used.

    • History of neuroleptic malignant syndrome (NMS) or NMS-like syndromes, or non-traumatic rhabdomyolysis.

    • History of or current cancer disease, which in the investigator's opinion would exclude the subject from the study (e.g. melanoma, prostate cancer).

    • Unstable active narrow-angle or unstable wide-angle glaucoma.

    • History of or current evidence of any relevant disease in the context of this study, i.e. with respect to the safety of the subject or related to the study conditions, e.g. which may influence the absorption or metabolism (such as a relevant liver disease) of the IMP.

    • Pregnant or breastfeeding. V2 (Randomisation, Day 0)

    • Any abnormality in the liver enzymes (alanine aminotransferase and/or aspartate aminotransferase) > 2 times the upper limit of the normal range, in the screening laboratory tests results.

    • Plasma sodium < 130 mmol/L, white blood cell count < 3000 cells/mm3, or any other relevant clinical laboratory abnormality in the screening laboratory tests results that, in the investigator's opinion, may compromise the subject's safety.

    • Inadequate compliance to concomitant L-DOPA/DDCI and other anti-PD drugs during the Screening period.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Bial - Portela & Cª, S.A. S. Mamede do Coronado Portugal 4745-457

    Sponsors and Collaborators

    • Bial - Portela C S.A.

    Investigators

    • Principal Investigator: Joaquim Ferreira, MD, PhD, Centro Hospitalar de Lisboa Norte, EPE - Hospital de Staª Maria-Centro de Estudos Egas Moniz

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bial - Portela C S.A.
    ClinicalTrials.gov Identifier:
    NCT01568073
    Other Study ID Numbers:
    • BIA-91067-301
    • 2010-021860-13
    First Posted:
    Apr 2, 2012
    Last Update Posted:
    Sep 18, 2015
    Last Verified:
    Sep 1, 2015
    Keywords provided by Bial - Portela C S.A.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo Entacapone OPC 5mg OPC 25mg OPC 50mg
    Arm/Group Description Placebo 200 mg Entacapone - 200 mg OPC, Opicapone 5mg OPC, Opicapone 25mg OPC, Opicapone 50mg
    Period Title: Overall Study
    STARTED 121 122 122 119 116
    COMPLETED 110 107 110 108 107
    NOT COMPLETED 11 15 12 11 9

    Baseline Characteristics

    Arm/Group Title Placebo Entacapone OPC 5mg OPC 25mg OPC 50mg Total
    Arm/Group Description Placebo 200 mg Entacapone - 200 mg OPC, Opicapone 5mg OPC, Opicapone 25mg OPC, Opicapone 50mg Total of all reporting groups
    Overall Participants 121 122 122 119 116 600
    Age, Customized (participants) [Number]
    <70 years
    80
    66.1%
    84
    68.9%
    87
    71.3%
    81
    68.1%
    81
    69.8%
    413
    68.8%
    ≥70 years
    41
    33.9%
    38
    31.1%
    35
    28.7%
    38
    31.9%
    35
    30.2%
    187
    31.2%
    Sex: Female, Male (Count of Participants)
    Female
    50
    41.3%
    46
    37.7%
    51
    41.8%
    52
    43.7%
    47
    40.5%
    246
    41%
    Male
    71
    58.7%
    76
    62.3%
    71
    58.2%
    67
    56.3%
    69
    59.5%
    354
    59%

    Outcome Measures

    1. Primary Outcome
    Title Efficacy of 3 BIA 9-1067 (5 mg, 25 mg, and 50 mg) Compared With 200 mg of Entacapone or Placebo,
    Description The primary efficacy variable will be the change from baseline in absolute OFF-time at the end of the DB period, This results refers when administered with the existing treatment of L-DOPA plus a DDCI, in patients with PD and end-of-dose motor fluctuations
    Time Frame 14 to 15 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo Entacapone OPC 5mg OPC 25mg OPC 50mg
    Arm/Group Description Placebo 200 mg Entacapone - 200 mg OPC, Opicapone 5mg OPC, Opicapone 25mg OPC, Opicapone 50mg
    Measure Participants 112 104 110 105 106
    Mean (Standard Error) [minutes]
    -56.0
    (13.38)
    -96.3
    (13.40)
    -91.3
    (13.46)
    -85.9
    (13.69)
    -116.8
    (13.97)
    2. Secondary Outcome
    Title Total UPDRS SCORE (I, II (ON), and III)
    Description Total UPDRS (Part I, II (ON) and III) UPDRS I evaluation of mentation, behavior, and mood UPDRS II self-evaluation of the activities of daily life (ADLs) including speech, swallowing, handwriting, dressing, hygiene, falling, salivating, turning in bed, walking, and cutting food UPDRS III clinician-scored monitored motor evaluation The UPDRS I, II and III scores and subscores are calculated as the sum of all individual items. If one or two items in a scale are missing, they will be imputed with the mean of the non-missing items of that scale. Subscale has 0-4 ratings, where 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe The final cumulative score will range from 0 (no disability) to 199 (total disability).
    Time Frame 14 to 15 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo Entacapone OPC 5mg OPC 25mg OPC 50mg
    Arm/Group Description Placebo 200 mg Entacapone - 200 mg OPC, Opicapone 5mg OPC, Opicapone 25mg OPC, Opicapone 50mg
    Measure Participants 114 111 113 111 109
    Baseline (Day 0)
    37.6
    (16.56)
    35.4
    (19.98)
    38.2
    (16.16)
    40.1
    (18.56)
    38.8
    (18.99)
    Endpoint (14 to 15 weeks)
    32.1
    (14.87)
    29.8
    (18.69)
    31.0
    (15.98)
    32.0
    (15.61)
    31.5
    (18.72)
    Change from Baseline to Endpoint
    -5.6
    (10.03)
    -6.0
    (11.69)
    -7.6
    (9.96)
    -7.6
    (9.76)
    -6.5
    (10.14)
    3. Secondary Outcome
    Title Parkinson's Disease Sleep Scale (PDSS)
    Description The Parkinson's disease Sleep Scale (PDSS) is a specific scale for the assessment of sleep disturbances in subjects with PD. The PDSS score is calculated as the sum of all single items. If one or two items are missing, they will be imputed with the mean of the non-missing items. If three or more items are missing, no imputation will be done and the score will be set to missing. Subscale has 0-10 ratings, where 0 = severe and 10 = normal The PDSS total score is a sum score of all 15 questions and ranges from 0 to 150, with lower scores meaning more disability.
    Time Frame 14 to 15 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo Entacapone OPC 5mg OPC 25mg OPC 50mg
    Arm/Group Description Placebo 200 mg Entacapone - 200 mg OPC, Opicapone 5mg OPC, Opicapone 25mg OPC, Opicapone 50mg
    Measure Participants 112 111 111 110 108
    Baseline
    97.5
    (24.97)
    100.7
    (25.46)
    97.8
    (22.55)
    92.7
    (26.85)
    98.0
    (22.19)
    Visit 5
    97.6
    (24.20)
    102.5
    (26.20)
    103.8
    (22.08)
    101.7
    (23.92)
    100.2
    (24.37)
    Visit 7
    97.7
    (25.30)
    103.2
    (24.86)
    102.8
    (22.78)
    100.6
    (23.75)
    100.7
    (24.20)
    Endpoint (14 to 15 weeks)
    98.5
    (25.81)
    102.8
    (24.98)
    102.9
    (22.61)
    100.4
    (23.75)
    100.9
    (24.05)
    4. Secondary Outcome
    Title Non-motor Symptoms Scale (NMSS)
    Description The Non-motor Symptoms Scale (NMSS) consists of 30 questions, covering 9 dimensions, whereby each item is scored for severity and frequency: Severity None 0 Mild (symptoms present but causes little distress) 1 Moderate (some distress or disturbance to subject) 2 Severe (major source of distress or disturbance to subject) 3 Frequency Rarely (<1/wk) 1 Often (1/wk) 2 Frequent (several times per week) 3 Very Frequent (daily or all the time) 4 The product of frequency and severity is calculated for each item and each dimension score is defined as the sum of the frequency*severity of the respective items. If frequency or severity of a single item is missing, the domain score will not be calculated. The NMSS total score is defined as the sum of all domain scores. The NMSS total score is calculated by adding all domain scores (0-360), and lower scores mean less disability.
    Time Frame 14 to 15 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo Entacapone OPC 5mg OPC 25mg OPC 50mg
    Arm/Group Description Placebo 200 mg Entacapone - 200 mg OPC, Opicapone 5mg OPC, Opicapone 25mg OPC, Opicapone 50mg
    Measure Participants 118 119 117 115 114
    Baseline
    38.8
    (29.20)
    32.1
    (25.09)
    36.1
    (26.67)
    39.8
    (30.18)
    36.4
    (28.02)
    Visit 5
    33.4
    (27.91)
    27.9
    (21.53)
    30.2
    (24.36)
    34.0
    (24.83)
    30.2
    (21.56)
    Visit 7
    32.3
    (25.75)
    27.5
    (21.91)
    29.5
    (24.30)
    34.6
    (25.39)
    33.7
    (30.24)
    Endpoint
    32.0
    (25.71)
    27.5
    (21.82)
    29.5
    (24.30)
    34.4
    (25.32)
    33.4
    (30.23)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Placebo Entacapone OPC 5mg OPC 25mg OPC 50mg
    Arm/Group Description Placebo 200 mg Entacapone - 200 mg OPC, Opicapone 5mg OPC, Opicapone 25mg OPC, Opicapone 50mg
    All Cause Mortality
    Placebo Entacapone OPC 5mg OPC 25mg OPC 50mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo Entacapone OPC 5mg OPC 25mg OPC 50mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/121 (5%) 8/122 (6.6%) 4/122 (3.3%) 1/119 (0.8%) 4/115 (3.5%)
    Cardiac disorders
    ANGINA UNSTABLE 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 1/115 (0.9%)
    COR PULMONALE ACUTE 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    CORONARY ARTERY DISEASE 0/121 (0%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 1/115 (0.9%)
    Eye disorders
    VISUAL IMPAIRMENT 1/121 (0.8%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    Gastrointestinal disorders
    CONSTIPATION 0/121 (0%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 1/115 (0.9%)
    DUODENITIS 1/121 (0.8%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    GASTRITIS 1/121 (0.8%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    INGUINAL HERNIA 0/121 (0%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 1/115 (0.9%)
    PANCREATITIS ACUTE 1/121 (0.8%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    Hepatobiliary disorders
    CHOLELITHIASIS 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    HEPATITIS ACUTE 1/121 (0.8%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    Infections and infestations
    CHOLECYSTITIS INFECTIVE 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    ERYSIPELAS 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    Injury, poisoning and procedural complications
    CONTUSION 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    FALL 0/121 (0%) 2/122 (1.6%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    FEMUR FRACTURE 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    NEAR DROWNING 1/121 (0.8%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    WRIST FRACTURE 0/121 (0%) 0/122 (0%) 1/122 (0.8%) 0/119 (0%) 0/115 (0%)
    Investigations
    HEPATIC ENZYME INCREASED 1/121 (0.8%) 0/122 (0%) 1/122 (0.8%) 0/119 (0%) 0/115 (0%)
    Musculoskeletal and connective tissue disorders
    BACK PAIN 1/121 (0.8%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    PAIN IN EXTREMITY 0/121 (0%) 0/122 (0%) 1/122 (0.8%) 0/119 (0%) 0/115 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA 0/121 (0%) 0/122 (0%) 1/122 (0.8%) 0/119 (0%) 0/115 (0%)
    BENIGN EAR NEOPLASM 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    BOWEN'S DISEASE 0/121 (0%) 0/122 (0%) 0/122 (0%) 1/119 (0.8%) 0/115 (0%)
    SUPERFICIAL SPREADING MELANOMA STAGE 1/121 (0.8%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    Nervous system disorders
    DYSKINESIA 0/121 (0%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 1/115 (0.9%)
    SYNCOPE 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    Renal and urinary disorders
    URINARY TRACT INFLAMMATION 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    Respiratory, thoracic and mediastinal disorders
    PNEUMONIA ASPIRATION 1/121 (0.8%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    PULMONARY EMBOLISM 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    Vascular disorders
    HYPERTENSION 1/121 (0.8%) 0/122 (0%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    ORTHOSTATIC HYPOTENSION 0/121 (0%) 1/122 (0.8%) 0/122 (0%) 0/119 (0%) 0/115 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo Entacapone OPC 5mg OPC 25mg OPC 50mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 43/121 (35.5%) 55/122 (45.1%) 48/122 (39.3%) 50/119 (42%) 55/115 (47.8%)
    Gastrointestinal disorders
    CONSTIPATION 3/121 (2.5%) 5/122 (4.1%) 4/122 (3.3%) 0/119 (0%) 7/115 (6.1%)
    NAUSEA 2/121 (1.7%) 8/122 (6.6%) 2/122 (1.6%) 3/119 (2.5%) 3/115 (2.6%)
    Injury, poisoning and procedural complications
    FALL 3/121 (2.5%) 5/122 (4.1%) 2/122 (1.6%) 4/119 (3.4%) 1/115 (0.9%)
    Investigations
    WEIGHT DECREASED 0/121 (0%) 2/122 (1.6%) 1/122 (0.8%) 0/119 (0%) 4/115 (3.5%)
    Musculoskeletal and connective tissue disorders
    BACK PAIN 6/121 (5%) 1/122 (0.8%) 4/122 (3.3%) 3/119 (2.5%) 0/115 (0%)
    MUSCLE SPASMS 1/121 (0.8%) 1/122 (0.8%) 1/122 (0.8%) 4/119 (3.4%) 1/115 (0.9%)
    Nervous system disorders
    DYSKINESIA 5/121 (4.1%) 10/122 (8.2%) 17/122 (13.9%) 9/119 (7.6%) 18/115 (15.7%)
    DIZZINESS 1/121 (0.8%) 5/122 (4.1%) 2/122 (1.6%) 6/119 (5%) 3/115 (2.6%)
    HEADACHE 3/121 (2.5%) 3/122 (2.5%) 1/122 (0.8%) 2/119 (1.7%) 4/115 (3.5%)
    SOMNOLENCE 2/121 (1.7%) 0/122 (0%) 1/122 (0.8%) 4/119 (3.4%) 2/115 (1.7%)
    Psychiatric disorders
    INSOMNIA 1/121 (0.8%) 7/122 (5.7%) 2/122 (1.6%) 7/119 (5.9%) 7/115 (6.1%)
    HALLUCINATION 1/121 (0.8%) 1/122 (0.8%) 1/122 (0.8%) 6/119 (5%) 1/115 (0.9%)
    ANXIETY 4/121 (3.3%) 2/122 (1.6%) 1/122 (0.8%) 2/119 (1.7%) 2/115 (1.7%)
    Respiratory, thoracic and mediastinal disorders
    NASOPHARYNGITIS 4/121 (3.3%) 2/122 (1.6%) 4/122 (3.3%) 2/119 (1.7%) 1/115 (0.9%)
    Skin and subcutaneous tissue disorders
    HYPERHIDROSIS 4/121 (3.3%) 1/122 (0.8%) 1/122 (0.8%) 2/119 (1.7%) 0/115 (0%)
    Vascular disorders
    HYPERTENSION 3/121 (2.5%) 2/122 (1.6%) 4/122 (3.3%) 2/119 (1.7%) 2/115 (1.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Results Point of Contact

    Name/Title Head of Clinical Research
    Organization Bial - Portela & Cª, S.A.
    Phone +351 229 866 100
    Email jose.rocha@bial.com
    Responsible Party:
    Bial - Portela C S.A.
    ClinicalTrials.gov Identifier:
    NCT01568073
    Other Study ID Numbers:
    • BIA-91067-301
    • 2010-021860-13
    First Posted:
    Apr 2, 2012
    Last Update Posted:
    Sep 18, 2015
    Last Verified:
    Sep 1, 2015