Dose-Finding Safety Study of BIIB014 in Combination With Levodopa in Moderate to Late Stage Parkinson's Disease

Study Overview
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Brief Summary
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The main purpose of this study is to determine the safety of BIIB014 and how well BIIB014 is tolerated when given at different doses to patients with moderate to late-stage Parkinson's Disease who are also taking the Parkinson's medication, levodopa (L-DOPA). This study will also explore: the pharmacokinetics of BIIB014 in Parkinson's patients who are also taking L-DOPA (this will be done by measuring the levels of BIIB014 in the blood at several different times during the study), and the activity of BIIB014 when given to Parkinson's patients who are also taking L-DOPA (this will be done by performing different Parkinson's Disease assessments during the study to examine change in waking OFF time, change in time with troublesome dyskinesia, change in Unified PD Rating Scale (UPDRS) scores, and Clinical Global Improvement). Patients who enter this study will be randomly assigned to receive either BIIB014 or a placebo but because the study is blinded, neither they nor their study doctor will know which study treatment they are taking. The study will be divided into 2 parts: Part A: a, rapid, sequential cohort, dose escalation to establish MTD, followed by Part B: a parallel-group exploration of the two highest tolerated doses versus placebo. Note: As Part A of the study is now concluded, some of the study design information presented below (e.g., number of study arms) pertains only to Part B.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study of Single and Multiple Oral Dose Administration of BIIB014 in Subjects With Moderate to Late Stage Parkinson's Disease Who Are Also Receiving Treatment With Levodopa

Conditions
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Parkinson's Disease

Intervention / Treatment
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* Drug: BIIB014
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must carry a diagnosis of idiopathic PD according to UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria, and be Hoehn & Yahr Stage II to IV (inclusive) when OFF. Must be on a stable dose of L-3,4-dihydroxyphenylalanine (L-DOPA)/carbidopa or L-DOPA/benserazide for at least 4 weeks prior to enrollment. Except for L-DOPA and certain allowed dopamine agonists, must not be receiving any other PD medications. (Current treatment with certain dopamine agonists is allowed but subjects must have been on a stable dose for at least 4 weeks prior to enrollment). Some subjects must demonstrate a definite end of L-DOPA dose wearing off (at least 2 hours OFF time per waking day) and must be able to keep accurate patient diaries of PD activity. Major Exclusion Criteria: A Mini Mental State Examination (MMSE) score <26. History or clinical features consistent with an atypical parkinsonian syndrome. Any significant non-Parkinson's central nervous system disorder. Any significant AXIS I psychiatric disease from the Diagnostic and Statistical Manual of Mental Disorders (DSM). Any previous surgical intervention for Parkinson's Disease. History of certain malignancies. History of severe allergic anaphylactic reactions to any drug. Clinically significant baseline electrocardiogram (ECG). Orthostatic hypotension. HbA1c >7.0%

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>BIIB014 at MTD from Part A | Drug: BIIB014<br>* oral administration of BIIB014 at dose to be specified from Part A, given daily for 8 weeks<br>|
| Other: 2<br>BIIB014 at dose immediately below MTD from Part A | Drug: BIIB014<br>* oral administration of BIIB014 at dose to be specified from Part A, given daily for 8 weeks<br>|
| Placebo Comparator: 3<br> | Drug: Placebo<br>* Matched placebo for MTD or MTD-1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and proportion of subjects with adverse events |  | up to end of study | 
| Assessment of clinical laboratory parameters |  | up to end of study | 
| Assessment of vital signs |  | up to end of study | 
| Assessment of ECG parameters. |  | up to end of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess PK by measuring concentrations of BIIB014 and its N-acetyl metabolite in blood plasma. |  | up to 24h following last dose (Part A only) | 
| Explore activity of BIIB014 by evaluating standard Parkinson's disease assessments |  | up to 8h following last dose (Part A); up to 24h following last dose (Part B only) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Moderate to late stage Parkinson's Disease