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

Parkinson's Disease Clinical Trial

— 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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01227655
• Other study ID #: BIA-91067-302
• Secondary ID: 2010-022366-27BI
• Status: Completed
• Phase: Phase 3
• First received: October 22, 2010
• Last updated: September 21, 2015
• Start date: March 2011
• Est. completion date: July 2012

Study information

• Verified date: September 2015
• Source: Bial - Portela C S.A.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyBelgium: Federal Agency for Medicinal Products and Health ProductsEstonia: The State Agency of MedicineCzech Republic: State Institute for Drug ControlIsrael: Ministry of HealthAustralia: National Health and Medical Research CouncilIndia: Central Drugs Standard Control OrganizationArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaChile: Instituto de Salud Pública de ChileSouth Africa: Medicines Control CouncilSouth Korea: Korea Food and Drug Administration (KFDA)
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 427
• Est. completion date: July 2012
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 83 Years

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Parkinson Disease
• Parkinson's Disease

Intervention

Drug:
• BIA 9-1067
Capsules will be used.
• Placebo
comparator
• Levodopa

• Carbidopa
DOPA decarboxylase inhibitor (DDCI)
• Benserazide
DOPA decarboxylase inhibitor

Locations

Country	Name	City	State
Portugal	Bial - Portela & Cª, S.A.	S. Mamede do Coronado

Sponsors (1)

Lead Sponsor	Collaborator
Bial - Portela C S.A.

Country where clinical trial is conducted

Portugal, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	14-15 weeks	No
Secondary	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).	14-15 weeks	No
Secondary	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.	14-15 weeks	No
Secondary	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.	14-15 weeks	No