Efficacy of Orally Disintegrating Selegiline in Parkinson's Patients Experiencing Adverse Effects With Dopamine Agonists

NCT ID: NCT00443872

Last Updated: 2014-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 77 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2008-12-31

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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

orally disintegrating selegiline

This is a one arm open label study of patients who are experiencing a dopamine agonist (DA) related adverse effects (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder. All subjects received orally disintegrating selegiline.

Group Type: OTHER

orally disintegrating selegiline (Zelapar)

Intervention Type: DRUG

1.25 mg once daily orally disintegrating selegiline for 6 weeks with an increase to 2.5 mg once daily orally disintegrating selegiline for remaining 6 weeks if tolerated

Interventions

orally disintegrating selegiline (Zelapar)

1.25 mg once daily orally disintegrating selegiline for 6 weeks with an increase to 2.5 mg once daily orally disintegrating selegiline for remaining 6 weeks if tolerated

Intervention Type: DRUG

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bausch Health Americas, Inc.

INDUSTRY

Sponsor Role: collaborator

Parkinson's Disease and Movement Disorder Center of Boca Raton

OTHER

Sponsor Role: lead

Responsible Party

Stuart Isaacson

MD, Director of the Parkinson's Disease and Movement Disorder Center of Boca Raton

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rajesh Pahwa, MD

Role: PRINCIPAL_INVESTIGATOR

University of Kansas Medical Center

Locations

University of California - Irvine

Irvine, California, United States

Coastal Neurological Medical Group, Inc

La Jolla, California, United States

University of Southern California

Los Angeles, California, United States

The Parkinson's Institute

Sunnyvale, California, United States

Parkinson's Disease and Movement Disorder Center of Boca Raton

Boca Raton, Florida, United States

University of South Florida

Tampa, Florida, United States

Methodist Plaza Speciality Clinic

Des Moines, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Harvard Vanguard Medical Associates

Boston, Massachusetts, United States

Henry Ford Health Center - Franklin Pointe

Southfield, Michigan, United States

Struthers Parkinson's Center

Golden Valley, Minnesota, United States

University of Toledo

Toledo, Ohio, United States

NeuroHealth Parkinson Disease and Movement Disorder Center

Warwick, Rhode Island, United States

Neurology Specialists Dallas

Dallas, Texas, United States

ETMC Neurological Institute

Tyler, Texas, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 19855267 (View on PubMed)

Other Identifiers

VAL-1.0-IV

Identifier Type: -

Identifier Source: org_study_id