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

Primary Purpose

Parkinson's Disease

Status
Completed
Phase
Phase 3
Locations
Portugal
Study Type
Interventional
Intervention
BIA 9-1067
Placebo
Levodopa
Carbidopa
Benserazide
Sponsored by
Bial - Portela C S.A.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson, PD, Wearing-off, Levodopa/DDCI

Eligibility Criteria

30 Years - 83 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Bial - Portela & Cª, S.A.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

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

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

Placebo

Arm Description

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

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

PLC, Placebo

Outcomes

Primary Outcome Measures

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)
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

UPDRS (Unified Parkinson's Disease Rating Scale) Sections I (ON), II (ON and OFF), and III (ON)
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).
Parkinson's Disease Sleep Scale (PDSS)
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.
Non-motor Symptoms Scale (NMSS)
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.

Full Information

First Posted
October 22, 2010
Last Updated
September 21, 2015
Sponsor
Bial - Portela C S.A.
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1. Study Identification

Unique Protocol Identification Number
NCT01227655
Brief Title
Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson's Disease Patients.
Acronym
BIPARKII
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 Type
Interventional

2. Study Status

Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
March 2011 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
July 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bial - Portela C S.A.

4. Oversight

Data Monitoring Committee
Yes

5. 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson, PD, Wearing-off, Levodopa/DDCI

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
427 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BIA 9-1067 25 mg once daily (QD).
Arm Type
Experimental
Arm Description
BIA 9-1067, OPC, Opicapone 25 mg once daily (QD).
Arm Title
BIA 9-1067 50 mg once daily (QD).
Arm Type
Experimental
Arm Description
BIA 9-1067, OPC, Opicapone 50 mg once daily (QD).
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
PLC, Placebo
Intervention Type
Drug
Intervention Name(s)
BIA 9-1067
Other Intervention Name(s)
Opicapone
Intervention Description
Capsules will be used.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo; PLC
Intervention Description
comparator
Intervention Type
Drug
Intervention Name(s)
Levodopa
Other Intervention Name(s)
L-Dopa
Intervention Type
Drug
Intervention Name(s)
Carbidopa
Intervention Description
DOPA decarboxylase inhibitor (DDCI)
Intervention Type
Drug
Intervention Name(s)
Benserazide
Intervention Description
DOPA decarboxylase inhibitor
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
83 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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. Exclusion Criteria: 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: 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. Treatment with apomorphine 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 investigational medicinal product 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.
Facility Information:
Facility Name
Bial - Portela & Cª, S.A.
City
S. Mamede do Coronado
ZIP/Postal Code
4745-457
Country
Portugal

12. IPD Sharing Statement

Citations:
PubMed Identifier
28027332
Citation
Lees AJ, Ferreira J, Rascol O, Poewe W, Rocha JF, McCrory M, Soares-da-Silva P; BIPARK-2 Study Investigators. Opicapone as Adjunct to Levodopa Therapy in Patients With Parkinson Disease and Motor Fluctuations: A Randomized Clinical Trial. JAMA Neurol. 2017 Feb 1;74(2):197-206. doi: 10.1001/jamaneurol.2016.4703.
Results Reference
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Efficacy and Safety of BIA 9-1067 in Idiopathic Parkinson's Disease Patients.

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