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

NCT00443872 | Completed Phase 4 Results

• 1 other identifier: VAL-1.0-IV
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 17

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.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; Dopamine agonist adverse effects; MAO-B inhibitor; orally disintegrating selegiline; Zelapar

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With Reduction in Adverse Events

  The primary outcome measure was the reduction of daytime sleepiness, hallucinations, pedal edema, and impulse control disorders after a reduction of dopamine agonist dose with the addition of an monoamine oxidase (MAO)-B inhibitor (orally disintegrating selegiline). Percentages of participants with reduction in individual adverse events as well as reduction in any adverse events are reported.

  3 Months

• Epworth Sleepiness Scale Score for Those With Daytime Sleepiness

  This is a measure of daytime sleepiness. The test is a list of eight situations in which one rates their tendency to become sleepy on a scale of 0, no change of dozing to 3, high chance of dozing. The total score ranges fro 0-24, with higher values representing excessive sleepiness. A score of greater than 10 represents clinically significant sleepiness.

  Baseline and 3 months

• Neuropsychiatric Inventory (NPI) Hallucinations Scale Score for Those With Hallucinations

  Report of hallucinations with insight maintained based on the hallucinations questions of the Neuropsychiatric Inventory (NPI). The participant and their caregiver are asked a series of questions to determine if hallucinations are present. If present they rate the frequency of hallucinations on a scale of 1 (rarely, less than once a week) to 4, very often (once or more daily). They also rate the severity of the hallucinations, as mild (1 - present but harmless and cause little distress), moderate (2 - distressing and disruptive) or severe (3 - very disruptive, major source of behavioral disturbance, may need meds). The frequency and severity scores are multiplied (maximum score 12, with higher scores representing more distress/disability) for the total score.

  Baseline and 3 months

• Circumference of Lower Leg/Foot at Greatest Point of Swelling for Pedal Edema

  The circumference of the lower leg/ankle with the greatest swelling was measured using a standard tape measure at baseline and 12 weeks for both the right and left ankles.

  Baseline and 3 months

• Barratt Impulsiveness Scale Score for Those With Impulsive Behavior

  This is a measure of impulsiveness. There are 30 questions regarding the presence of impulsive and non-impulsive behaviors each scored from 1 (rarely/never) to 4 (almost always/always). The total score reflects the sum of the 30 items. A higher score represents more impulsiveness.

  Baseline and 3 months

Secondary Outcomes (5)

• Unified Parkinson's Disease Rating Scale (UPDRS) Scores

  Baseline and 3 months

• PDQ-39 Quality of Life Assessment Total Scores

  Baseline and 3 months

• Beck Depression Inventory for All Subjects

  Baseline and 3 months

• Beck Anxiety Inventory Scores for All Subjects

  Baseline and 3 months

• Mini Mental State Examination (MMSE) Scores for All Subjects

  Baseline and 3 months

Study Arms (1)

orally disintegrating selegiline

OTHER

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.

Drug: orally disintegrating selegiline (Zelapar)

Interventions

orally disintegrating selegiline (Zelapar) 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

orally disintegrating selegiline

Eligibility Criteria

• Age: 30 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Parkinson's Disease and Movement Disorder Center of Boca Raton: lead
• Bausch Health Americas, Inc.: collaborator

Study Sites (17)

University of California - Irvine

Irvine, California, 92697, United States

Location

Coastal Neurological Medical Group, Inc

La Jolla, California, 92037, United States

Location

University of Southern California

Los Angeles, California, 90093, United States

Location

The Parkinson's Institute

Sunnyvale, California, 94085, United States

Location

Parkinson's Disease and Movement Disorder Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Methodist Plaza Speciality Clinic

Des Moines, Iowa, 50309, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Harvard Vanguard Medical Associates

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health Center - Franklin Pointe

Southfield, Michigan, 48034, United States

Location

Struthers Parkinson's Center

Golden Valley, Minnesota, 55427, United States

Location

University of Toledo

Toledo, Ohio, 43614, United States

Location

NeuroHealth Parkinson Disease and Movement Disorder Center

Warwick, Rhode Island, 02886, United States

Location

Neurology Specialists Dallas

Dallas, Texas, 75231, United States

Location

ETMC Neurological Institute

Tyler, Texas, 75701, United States

Location

Related Publications (1)

• 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.

  PMID: 19855267 RESULT

MeSH Terms

Conditions

Parkinson Disease

Interventions

Selegiline

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr. Kelly Lyons
• Organization: University of Kansas Medical Center

klyons@kumc.edu

9135887159

Study Officials

• Rajesh Pahwa, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Director of the Parkinson's Disease and Movement Disorder Center of Boca Raton

Study Record Dates

• First Submitted: March 3, 2007
• First Posted: March 6, 2007
• Study Start: March 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: December 1, 2008
• Last Updated: October 31, 2014
• Results First Posted: October 31, 2014

Record last verified: 2014-10

Locations

US (17)