Clinical trial NCT00438607: Dose-Finding Safety Study of BIIB014 in Combination With Levodopa in Moderate to Late Stage Parkinson's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Keywords: Moderate to late stage Parkinson's Disease
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2007-02-22
Enrollment: 83
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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:

1. 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
2. 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.


Eligibility criteria: 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%

Primary outcomes:
measure: Number and proportion of subjects with adverse events
timeFrame: up to end of study
measure: Assessment of clinical laboratory parameters
timeFrame: up to end of study
measure: Assessment of vital signs
timeFrame: up to end of study
measure: Assessment of ECG parameters.
timeFrame: up to end of study
Secondary outcomes:
measure: Assess PK by measuring concentrations of BIIB014 and its N-acetyl metabolite in blood plasma.
timeFrame: up to 24h following last dose (Part A only)
measure: Explore activity of BIIB014 by evaluating standard Parkinson's disease assessments
timeFrame: up to 8h following last dose (Part A); up to 24h following last dose (Part B only)
Other outcomes:
Locations:
city: Bangalore
country: India
facility: Research Sites
city: Chennai
country: India
facility: Research Site
city: Hyderabaad
country: India
facility: Research Site
city: Ludhiana
country: India
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Secunderabad
country: India
facility: Research Site
city: Ashkelon
country: Israel
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Ramat-Gan
country: Israel
facility: Research Site
city: Tel Aviv
country: Israel
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Norwich
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Cambridge, MA USA
name: Biogen Idec
role: STUDY_DIRECTOR
References: