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

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: BIIB014; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • Bangalore, India
    • Research Sites
  • Chennai, India
    • Research Site
  • Hyderabaad, India
    • Research Site
  • Ludhiana, India
    • Research Site
  • Mumbai, India
    • Research Site
  • New Delhi, India
    • Research Site
  • Secunderabad, India
    • Research Site
• Israel
  • Ashkelon, Israel
    • Research Site
  • Jerusalem, Israel
    • Research Site
  • Ramat-Gan, Israel
    • Research Site
  • Tel Aviv, Israel
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom
    • Research Site
  • Manchester, United Kingdom
    • Research Site
  • Norwich, United Kingdom
    • Research Site
  • Salford, United Kingdom
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: Biogen
• Investigators: Study Director: Biogen Idec, Cambridge, MA USA

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: February 20, 2007
• First Submitted That Met QC Criteria: February 20, 2007
• First Posted (Estimate): February 22, 2007

Study Record Updates

• Last Update Posted (Estimate): July 13, 2009
• Last Update Submitted That Met QC Criteria: July 10, 2009
• Last Verified: July 1, 2009

More Information

Terms related to this study

• Keywords: Moderate to late stage Parkinson's Disease
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Purinergic Antagonists; Purinergic Agents; Purinergic P1 Receptor Antagonists; Adenosine A2 Receptor Antagonists; 3-(4-amino-3-methylbenzyl)-7-(2-furyl)-3H-(1,2,3)triazolo(4,5-d)pyrimidine-5-amine
• Other Study ID Numbers: 204PD202; EUDRA CT NO: 2006-003490-27; ISCRTN 12870393