BIPARKII: Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson's Disease Patients.

Sponsor
Bial - Portela C S.A. (Industry)
Overall Status
Completed
CT.gov ID
NCT01227655
Collaborator
(none)
427
1
3
16
26.6

Study Details

Study Description

Brief Summary

Parkinson's disease (PD) is a neurodegenerative disorder of unknown aetiology with an estimated incidence of 4.5-16/100,000 persons/year.

BIA 9-1067 is currently being developed by BIAL (Portela & Cª,S.A.) to be used in addition to L-DOPA (Levodopa) /carbidopa or L-DOPA (Levodopa) / preparations in PD patients. Promising results have been obtained for BIA 9-1067 in previous studies.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

This study aims to demonstrate the efficacy and safety of BIA 9-1067 used in addition to L-DOPA/DDCI to control the "wearing-off" phenomenon in patients with PD.

DDCI (DOPA decarboxylase inhibitors): benserazide and carbidopa

Study Design

Study Type:
Interventional
Actual Enrollment :
427 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-controlled, Parallel-group, Multicentre Clinical Study.
Study Start Date :
Mar 1, 2011
Actual Primary Completion Date :
Jul 1, 2012
Actual Study Completion Date :
Jul 1, 2012

Arms and Interventions

Arm Intervention/Treatment
Experimental: BIA 9-1067 25 mg once daily (QD).

BIA 9-1067, OPC, Opicapone 25 mg once daily (QD).

Drug: BIA 9-1067
Capsules will be used.
Other Names:
  • Opicapone
  • Drug: Levodopa
    Other Names:
  • L-Dopa
  • Drug: Carbidopa
    DOPA decarboxylase inhibitor (DDCI)

    Drug: Benserazide
    DOPA decarboxylase inhibitor

    Experimental: BIA 9-1067 50 mg once daily (QD).

    BIA 9-1067, OPC, Opicapone 50 mg once daily (QD).

    Drug: BIA 9-1067
    Capsules will be used.
    Other Names:
  • Opicapone
  • Drug: Levodopa
    Other Names:
  • L-Dopa
  • Drug: Carbidopa
    DOPA decarboxylase inhibitor (DDCI)

    Drug: Benserazide
    DOPA decarboxylase inhibitor

    Placebo Comparator: Placebo

    PLC, Placebo

    Drug: Placebo
    comparator
    Other Names:
  • placebo; PLC
  • Drug: Levodopa
    Other Names:
  • L-Dopa
  • Drug: Carbidopa
    DOPA decarboxylase inhibitor (DDCI)

    Drug: Benserazide
    DOPA decarboxylase inhibitor

    Outcome Measures

    Primary Outcome Measures

    1. Efficacy of 2 BIA 9-1067 (25 mg, and 50 mg) Compared With Placebo, When Administered With the Existing Treatment of L-DOPA Plus a DDCI (DOPA Decarboxylase Inhibitor) [14-15 weeks]

      Efficacy of 2 BIA 9-1067 (25 mg, and 50 mg) compared with placebo, when administered with the existing treatment of L-DOPA plus a DDCI (DOPA decarboxylase inhibitor), in patients with PD and end-of-dose motor fluctuations. The primary efficacy variable will be the change from baseline in absolute OFF-time at the end of the DB period.

    Secondary Outcome Measures

    1. UPDRS (Unified Parkinson's Disease Rating Scale) Sections I (ON), II (ON and OFF), and III (ON) [14-15 weeks]

      Total UPDRS SCORE (I, II (ON), and III) Change from Baseline to Endpoint 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) [14-15 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) [14-15 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:
    1. Able to comprehend and willing to sign an informed consent form.

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

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

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

    5. Treated with L-DOPA/DDCI for at least 1 year with clear clinical improvement.

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

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

    8. 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.

    Exclusion Criteria:
    1. Non-idiopathic PD (atypical parkinsonism, secondary [acquired or symptomatic] parkinsonism, Parkinson-plus syndrome).

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

    3. Severe and/or unpredictable OFF periods.

    4. Treatment with prohibited medication: entacapone, tolcapone, neuroleptics, venlafaxine, MAO inhibitors (except selegiline up to 10 mg/day in oral formulation or 1.25 mg/day in buccal absorption formulation or rasagiline up to 1mg/day), or antiemetics with antidopaminergic action (except domperidone) within the month before screening.

    5. Treatment with apomorphine within the month before screening or likely to be needed at any time during the study.

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

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

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

    9. Any investigational medicinal product within the 3 months (or within 5 half-lives, whichever is longer) before screening.

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

    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

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bial - Portela C S.A.
    ClinicalTrials.gov Identifier:
    NCT01227655
    Other Study ID Numbers:
    • BIA-91067-302
    • 2010-022366-27
    • BIA-91067-302
    First Posted:
    Oct 25, 2010
    Last Update Posted:
    Oct 19, 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 BIA 9-1067 25 mg BIA 9-1067 50 mg Placebo
    Arm/Group Description BIA 9-1067 once daily (QD). BIA 9-1067 once daily (QD). Placebo: comparator
    Period Title: Overall Study
    STARTED 129 154 144
    Safety Set 125 150 136
    Full Analysis Set 125 147 135
    COMPLETED 118 128 130
    NOT COMPLETED 11 26 14

    Baseline Characteristics

    Arm/Group Title BIA 9-1067 25 mg BIA 9-1067 50 mg Placebo Total
    Arm/Group Description BIA 9-1067 once daily (QD). BIA 9-1067 once daily (QD). Placebo: comparator Total of all reporting groups
    Overall Participants 125 147 135 407
    Age, Customized (participants) [Number]
    <70 years
    96
    76.8%
    96
    65.3%
    107
    79.3%
    299
    73.5%
    ≥70 years
    29
    23.2%
    51
    34.7%
    28
    20.7%
    108
    26.5%
    Sex: Female, Male (Count of Participants)
    Female
    82
    65.6%
    89
    60.5%
    71
    52.6%
    242
    59.5%
    Male
    43
    34.4%
    58
    39.5%
    64
    47.4%
    165
    40.5%

    Outcome Measures

    1. Primary Outcome
    Title Efficacy of 2 BIA 9-1067 (25 mg, and 50 mg) Compared With Placebo, When Administered With the Existing Treatment of L-DOPA Plus a DDCI (DOPA Decarboxylase Inhibitor)
    Description Efficacy of 2 BIA 9-1067 (25 mg, and 50 mg) compared with placebo, when administered with the existing treatment of L-DOPA plus a DDCI (DOPA decarboxylase inhibitor), in patients with PD and end-of-dose motor fluctuations. The primary efficacy variable will be the change from baseline in absolute OFF-time at the end of the DB period.
    Time Frame 14-15 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title BIA 9-1067 25 mg BIA 9-1067 50 mg Placebo
    Arm/Group Description BIA 9-1067 once daily (QD). BIA 9-1067 once daily (QD). Placebo: comparator
    Measure Participants 125 147 135
    Mean (Standard Deviation) [minutes]
    -102.8
    (159.42)
    -124.0
    (178.23)
    -64.5
    (155.35)
    2. Secondary Outcome
    Title UPDRS (Unified Parkinson's Disease Rating Scale) Sections I (ON), II (ON and OFF), and III (ON)
    Description Total UPDRS SCORE (I, II (ON), and III) Change from Baseline to Endpoint 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 14-15 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title BIA 9-1067 25 mg BIA 9-1067 50 mg Placebo
    Arm/Group Description BIA 9-1067 once daily (QD). BIA 9-1067 once daily (QD). Placebo: comparator
    Measure Participants 125 147 135
    Baseline
    30.8
    (16.88)
    31.7
    (17.55)
    31.5
    (17.00)
    Endpoint
    26.6
    (16.40)
    28.7
    (18.11)
    28.1
    (16.78)
    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 14-15 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title BIA 9-1067 25 mg BIA 9-1067 50 mg Placebo
    Arm/Group Description BIA 9-1067 once daily (QD). BIA 9-1067 once daily (QD). Placebo: comparator
    Measure Participants 123 147 135
    Baseline
    95.75
    (28.026)
    102.62
    (25.116)
    101.76
    (26.729)
    Visit 5
    97.99
    (26.196)
    103.05
    (26.437)
    107.11
    (26.987)
    Visit 7
    98.79
    (25.280)
    103.25
    (26.752)
    105.39
    (28.643)
    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 14-15 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title BIA 9-1067 25 mg BIA 9-1067 50 mg Placebo
    Arm/Group Description BIA 9-1067 once daily (QD). BIA 9-1067 once daily (QD). Placebo: comparator
    Measure Participants 125 147 135
    Baseline
    38.2
    (29.40)
    36.7
    (30.88)
    38.2
    (33.37)
    Visit 5
    33.7
    (26.30)
    33.2
    (27.95)
    33.5
    (31.18)
    Visit 7
    35.0
    (29.88)
    31.5
    (28.47)
    31.6
    (29.88)

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title BIA 9-1067 25 mg BIA 9-1067 50 mg Placebo
    Arm/Group Description BIA 9-1067 once daily (QD). BIA 9-1067 once daily (QD). Placebo: comparator
    All Cause Mortality
    BIA 9-1067 25 mg BIA 9-1067 50 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    BIA 9-1067 25 mg BIA 9-1067 50 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/125 (3.2%) 9/150 (6%) 5/136 (3.7%)
    Gastrointestinal disorders
    NAUSEA 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    Hepatobiliary disorders
    CHOLECYSTITIS ACUTE 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    Infections and infestations
    PNEUMONIA 0/125 (0%) 0/150 (0%) 1/136 (0.7%)
    PYELONEPHRITIS ACUTE 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    Injury, poisoning and procedural complications
    FALL 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    FEMORAL NECK FRACTURE 0/125 (0%) 0/150 (0%) 1/136 (0.7%)
    HEAD INJURY 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    RADIUS FRACTURE 0/125 (0%) 0/150 (0%) 1/136 (0.7%)
    Investigations
    BIOPSY PROSTATE 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    Musculoskeletal and connective tissue disorders
    OSTEOARTHRITIS 1/125 (0.8%) 0/150 (0%) 0/136 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    BASAL CELL CARCINOMA 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    OVARIAN CANCER 0/125 (0%) 0/150 (0%) 1/136 (0.7%)
    Nervous system disorders
    COGNITIVE DISORDER 0/125 (0%) 0/150 (0%) 1/136 (0.7%)
    DYSKINESIA 1/125 (0.8%) 0/150 (0%) 0/136 (0%)
    Psychiatric disorders
    DELIRIUM FEBRILE 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    Renal and urinary disorders
    RENAL FAILURE 0/125 (0%) 0/150 (0%) 1/136 (0.7%)
    RENAL FAILURE ACUTE 1/125 (0.8%) 0/150 (0%) 0/136 (0%)
    URINARY RETENTION 1/125 (0.8%) 0/150 (0%) 0/136 (0%)
    Reproductive system and breast disorders
    CYSTOCELE 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    Respiratory, thoracic and mediastinal disorders
    PLEURAL EFFUSION 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    PULMONARY EMBOLISM 0/125 (0%) 1/150 (0.7%) 0/136 (0%)
    Other (Not Including Serious) Adverse Events
    BIA 9-1067 25 mg BIA 9-1067 50 mg Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 87/125 (69.6%) 108/150 (72%) 68/136 (50%)
    Gastrointestinal disorders
    Constipation 12/125 (9.6%) 10/150 (6.7%) 2/136 (1.5%)
    Dry mouth 13/125 (10.4%) 6/150 (4%) 1/136 (0.7%)
    Nausea 8/125 (6.4%) 5/150 (3.3%) 8/136 (5.9%)
    Infections and infestations
    Urinary tract infection 3/125 (2.4%) 9/150 (6%) 2/136 (1.5%)
    Injury, poisoning and procedural complications
    Fall 7/125 (5.6%) 7/150 (4.7%) 9/136 (6.6%)
    Investigations
    Blood CPK increased 5/125 (4%) 12/150 (8%) 5/136 (3.7%)
    Musculoskeletal and connective tissue disorders
    Pain in extremity 6/125 (4.8%) 4/150 (2.7%) 2/136 (1.5%)
    Arthralgia 5/125 (4%) 4/150 (2.7%) 1/136 (0.7%)
    Nervous system disorders
    Dyskinesia 30/125 (24%) 36/150 (24%) 11/136 (8.1%)
    Parkinson's disease 9/125 (7.2%) 6/150 (4%) 7/136 (5.1%)
    Headache 6/125 (4.8%) 6/150 (4%) 9/136 (6.6%)
    Dizziness 4/125 (3.2%) 6/150 (4%) 2/136 (1.5%)
    Somnolence 6/125 (4.8%) 3/150 (2%) 3/136 (2.2%)
    Psychiatric disorders
    Insomnia 10/125 (8%) 2/150 (1.3%) 3/136 (2.2%)
    Vascular disorders
    Hypertension 8/125 (6.4%) 6/150 (4%) 3/136 (2.2%)

    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:
    NCT01227655
    Other Study ID Numbers:
    • BIA-91067-302
    • 2010-022366-27
    • BIA-91067-302
    First Posted:
    Oct 25, 2010
    Last Update Posted:
    Oct 19, 2015
    Last Verified:
    Sep 1, 2015