Clinical trial NCT00443872: Efficacy of Orally Disintegrating Selegiline in Parkinson's Patients Experiencing Adverse Effects With Dopamine Agonists
Official title: Adding Orally Disintegrating Selegiline (Zelapar) to Patients Taking Dopamine Agonists and Experiencing Complications
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Parkinson's Disease
Keywords: Parkinson's disease
Dopamine agonist adverse effects
MAO-B inhibitor
orally disintegrating selegiline
Zelapar
Lead sponsor: Parkinson's Disease and Movement Disorder Center of Boca Raton
Sponsor class: OTHER
Collaborators: name: Bausch Health Americas, Inc.
First posted: 2007-03-06
Enrollment: 77
Sex: ALL
Minimum age (years): 30
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to determine if reducing or eliminating a dopamine agonist (DA) causing one of the side effects of daytime sleepiness, swelling of the lower legs or feet, hallucinations or impulsive behaviors while adding orally disintegrating selegiline can eliminate the adverse effect and maintain control of Parkinson's disease (PD) symptoms.

Detailed description: Parkinson's disease (PD) is a progressive neurodegenerative disease. Symptomatic therapy is primarily aimed at restoring dopamine function in the brain. Levodopa is the most effective symptomatic treatment; however, long term use is associated with motor fluctuations (periods of return of PD symptoms when medication effect wears off) and dyskinesia (drug induced involuntary movements including chorea and dystonia). Once patients develop motor fluctuations treatment options include increasing the frequency of levodopa dosing, switching to sustained-release levodopa, adding other therapies including monoamine oxidase type B (MAO-B) inhibitors, dopamine agonists, catechol-o-methyltransferase (COMT) inhibitors and in patients with severe motor fluctuations deep brain stimulation surgery. There are no good evidence based studies indicating whether the use of one of these class of drugs is superior to the other nor are there treatment algorithms that recommend which class of drug should be initiated when the patients initially develop motor fluctuations. It is believed that the efficacy of the different drug classes is similar. However, the frequency of adverse effects may differ between drug classes, but such studies are lacking. In clinical practice when patients develop adverse effects to a drug from one class, a drug from another class is substituted in an attempt to maintain efficacy with reduced adverse effects.

Dopamine agonists often have a higher risk of adverse effects compared to MAO B inhibitors. Therefore, the rationale for this study is that the addition of orally disintegrating selegiline after the reduction or discontinuation of the offending dopamine agonist will result in comparable efficacy with reduced adverse events. This study will assess the safety and efficacy of the addition of orally disintegrating selegiline in PD patients who are having adverse effects to dopamine agonists for which a dose reduction of the dopamine agonist is being considered. All patients in the study will receive orally disintegrating selegiline 1.25 mg once a day and the dose will be increased to 2.5 mg once a day if tolerated.

Comparisons: The status of the adverse event at the end of the study while on orally disintegrating selegiline will be compared to the adverse event at the start of the study. In addition, efficacy will be compared at the start of the study while on the dopamine agonist to the end of the study with orally disintegrating selegiline.

Eligibility criteria: Inclusion Criteria:

* Idiopathic Parkinson's disease (PD) confirmed by at least two of the following signs: resting tremor, bradykinesia,rigidity
* Male or female outpatients
* Age 30-90 years
* Current use of levodopa (stable for at least 1 month) and a dopamine agonist (pramipexole or ropinirole)
* Treatment response to current anti-parkinsonian medications in the opinion of the investigator
* Dopamine agonist adverse effect that in the opinion of the investigator requires a reduction or discontinuation of the dopamine agonist. The adverse effects must be in one of the following four categories and should not be so severe as to require immediate discontinuation of the dopamine agonist (i.e., hallucinations without insight, serious impulsive behavior resulting in significant loss or danger to the patient).

Daytime sleepiness - must score \>10 on Epworth Sleepiness Scale (ESS) at Baseline; Pedal edema - bothersome/concerning to patient; Hallucinations - insight should be maintained; Impulsive behavior - not including behaviors that are harmful to the patient requiring immediate discontinuation of the agonist.

* Daily off time
* Acceptable contraception for females of child bearing potential
* Willing and able to comply with study procedures.
* Willing and able to give written informed consent prior to beginning any study procedures.

Exclusion Criteria:

* Atypical parkinsonism due to drugs, metabolic disorders, encephalitis, trauma, or other neurodegenerative diseases.
* Significant cognitive or psychiatric impairment which, in the opinion of the investigator, would interfere with the ability to complete all the tests required in the protocol.
* Participation in another clinical drug trial within the previous four weeks.
* Patients currently on monoamine oxidase type A or B (MAO-A or B) inhibitors, meperidine, tramadol, methadone, propoxyphene, dextromethorphan, and mirtazapine.
* History of hypersensitivity or adverse reaction to selegiline or previous exposure to orally disintegrating selegiline
* History of melanoma
* Unstable/uncontrolled medical problems
* History of drug/alcohol abuse

Primary outcomes:
measure: Percentage of Participants With Reduction in Adverse Events
timeFrame: 3 Months
measure: Epworth Sleepiness Scale Score for Those With Daytime Sleepiness
timeFrame: Baseline and 3 months
measure: Neuropsychiatric Inventory (NPI) Hallucinations Scale Score for Those With Hallucinations
timeFrame: Baseline and 3 months
measure: Circumference of Lower Leg/Foot at Greatest Point of Swelling for Pedal Edema
timeFrame: Baseline and 3 months
measure: Barratt Impulsiveness Scale Score for Those With Impulsive Behavior
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Unified Parkinson's Disease Rating Scale (UPDRS) Scores
timeFrame: Baseline and 3 months
measure: PDQ-39 Quality of Life Assessment Total Scores
timeFrame: Baseline and 3 months
measure: Beck Depression Inventory for All Subjects
timeFrame: Baseline and 3 months
measure: Beck Anxiety Inventory Scores for All Subjects
timeFrame: Baseline and 3 months
measure: Mini Mental State Examination (MMSE) Scores for All Subjects
timeFrame: Baseline and 3 months
Other outcomes:
Locations:
city: Irvine
country: United States
facility: University of California - Irvine
state: California
city: La Jolla
country: United States
facility: Coastal Neurological Medical Group, Inc
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Sunnyvale
country: United States
facility: The Parkinson's Institute
state: California
city: Boca Raton
country: United States
facility: Parkinson's Disease and Movement Disorder Center of Boca Raton
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Des Moines
country: United States
facility: Methodist Plaza Speciality Clinic
state: Iowa
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Harvard Vanguard Medical Associates
state: Massachusetts
city: Southfield
country: United States
facility: Henry Ford Health Center - Franklin Pointe
state: Michigan
city: Golden Valley
country: United States
facility: Struthers Parkinson's Center
state: Minnesota
city: Toledo
country: United States
facility: University of Toledo
state: Ohio
city: Warwick
country: United States
facility: NeuroHealth Parkinson Disease and Movement Disorder Center
state: Rhode Island
city: Dallas
country: United States
facility: Neurology Specialists Dallas
state: Texas
city: Tyler
country: United States
facility: ETMC Neurological Institute
state: Texas
Study officials:
affiliation: University of Kansas Medical Center
name: Rajesh Pahwa, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lyons KE, Friedman JH, Hermanowicz N, Isaacson SH, Hauser RA, Hersh BP, Silver DE, Tetrud JW, Elmer LW, Parashos SA, Struck LK, Lew MF, Pahwa R. Orally disintegrating selegiline in Parkinson patients with dopamine agonist-related adverse effects. Clin Neuropharmacol. 2010 Jan-Feb;33(1):5-10. doi: 10.1097/WNF.0b013e3181b7926f.