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

• ClinicalTrials.gov Identifier: NCT01227655
• Recruitment Status: Completed
• First Posted: October 25, 2010
• Results First Posted: January 13, 2015
• Last Update Posted: October 19, 2015
• Sponsor: Bial - Portela C S.A.
• Information provided by (Responsible Party): Bial - Portela C S.A.

Tracking Information

• First Submitted Date: October 22, 2010
• First Posted Date: October 25, 2010
• Results First Submitted Date: November 26, 2014
• Results First Posted Date: January 13, 2015
• Last Update Posted Date: October 19, 2015
• Study Start Date: March 2011
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 12, 2015)

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) [ Time Frame: 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.

Original Primary Outcome Measures (submitted: October 22, 2010)

To investigate the efficacy of 2 different doses of BIA 9-1067 (25 mg and 50 mg),administered once a day, compared with placebo, when administered with the existing treatment of L-DOPA plus a DDCI, in patients with PD and end-of-dose motor fluctuations. [ Time Frame: 14-15 weeks ]

The primary efficacy variable will be the change from baseline in absolute OFF-time at the end of the DB period.

• Change History: Complete list of historical versions of study NCT01227655 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: January 12, 2015)

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

Original Secondary Outcome Measures (submitted: October 22, 2010)

• UPDRS Sections I (ON), II (ON and OFF), and III (ON) [ Time Frame: 14-15 weeks ]
• Parkinson's Disease Sleep Scale (PDSS) [ Time Frame: 14-15 weeks ]
• Non-motor Symptoms Scale (NMSS) [ Time Frame: 14-15 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Parkinson's Disease

Intervention

• Drug: BIA 9-1067
  Capsules will be used.
  Other Name: Opicapone
• Drug: Placebo
  comparator
  Other Name: placebo; PLC
• Drug: Levodopa
  Other Name: L-Dopa
• Drug: Carbidopa
  DOPA decarboxylase inhibitor (DDCI)
• Drug: Benserazide
  DOPA decarboxylase inhibitor

Study Arms

• Experimental: BIA 9-1067 25 mg once daily (QD).
  BIA 9-1067, OPC, Opicapone 25 mg once daily (QD).
  Interventions:

  • Drug: BIA 9-1067
  • Drug: Levodopa
  • Drug: Carbidopa
  • Drug: Benserazide
• Experimental: BIA 9-1067 50 mg once daily (QD).
  BIA 9-1067, OPC, Opicapone 50 mg once daily (QD).
  Interventions:

  • Drug: BIA 9-1067
  • Drug: Levodopa
  • Drug: Carbidopa
  • Drug: Benserazide
• Placebo Comparator: Placebo
  PLC, Placebo
  Interventions:

  • Drug: Placebo
  • Drug: Levodopa
  • Drug: Carbidopa
  • Drug: Benserazide

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 20, 2014): 427
• Original Estimated Enrollment (submitted: October 22, 2010): 405
• Actual Study Completion Date: July 2012
• Actual Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years to 83 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Portugal

Administrative Information

• NCT Number: NCT01227655
• Other Study ID Numbers: BIA-91067-302; 2010-022366-27 ( EudraCT Number ); BIA-91067-302 ( Other Identifier: Bial - Portela & Cª., S.A. )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Bial - Portela C S.A.
• Study Sponsor: Bial - Portela C S.A.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Bial - Portela C S.A.
• Verification Date: September 2015