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

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ClinicalTrials.gov Identifier: NCT00443872
Recruitment Status : Completed
First Posted : March 6, 2007
Results First Posted : October 31, 2014
Last Update Posted : October 31, 2014
Sponsor:
Collaborator:
Bausch Health Americas, Inc.
Information provided by (Responsible Party):
Stuart Isaacson, Parkinson's Disease and Movement Disorder Center of Boca Raton

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.

Condition or disease Intervention/treatment Phase
Parkinson's Disease Drug: orally disintegrating selegiline (Zelapar) Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Adding Orally Disintegrating Selegiline (Zelapar) to Patients Taking Dopamine Agonists and Experiencing Complications
Study Start Date : March 2007
Actual Primary Completion Date : September 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: 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




Primary Outcome Measures :
  1. Percentage of Participants With Reduction in Adverse Events [ Time Frame: 3 Months ]
    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.

  2. Epworth Sleepiness Scale Score for Those With Daytime Sleepiness [ Time Frame: Baseline and 3 months ]
    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.

  3. Neuropsychiatric Inventory (NPI) Hallucinations Scale Score for Those With Hallucinations [ Time Frame: Baseline and 3 months ]
    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.

  4. Circumference of Lower Leg/Foot at Greatest Point of Swelling for Pedal Edema [ Time Frame: Baseline and 3 months ]
    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.

  5. Barratt Impulsiveness Scale Score for Those With Impulsive Behavior [ Time Frame: Baseline and 3 months ]
    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.


Secondary Outcome Measures :
  1. Unified Parkinson's Disease Rating Scale (UPDRS) Scores [ Time Frame: Baseline and 3 months ]

    The UPDRS activities of daily living sub scale has 14 questions regarding the ability to perform daily activities like dressing, eating, etc. These questions are completed by the patient and each question has 5 responses ranging from 0 (no problems) to 4 (severe disability/cannot do). The total score for this sub scale is the sum of the scores for the 14 questions (higher scores represent greater disability), maximum score is 56.

    The motor assessment is completed by the investigator. There are 14 questions evaluating motor function in various body parts, representing 27 individual items (i.e., some questions, such as rigidity, are rated for 5 different body parts, other questions, such as finger tapping, are rated on both the right and left sides, and other questions are rated individually). Each item has 5 responses, 0 being none/no disability and 4 being the most severe disability. The 27 items are summed (higher scores represent greater disability); maximum score is 108.


  2. PDQ-39 Quality of Life Assessment Total Scores [ Time Frame: Baseline and 3 months ]
    The PDQ-39 is a measure of quality of life, it has 8 sub scales and a total score. For this study only the total score was examined. There are a total of 39 questions related to the following 8 sub scales: ability/difficulty to perform motor activities, ability to perform daily activities, cognition, emotional well being, stigma, social support, communication, bodily discomfort; each question with 5 responses (0, no/never, 4 always). The total score is calculated by adding the scores for each of the 39 items, dividing by 39 x 4 (maximum score for all 39 items) and then multiplying by 100 to get a percentage score ranging from 0-100 with 100 representing the most disability and greatest impact on quality of life.

  3. Beck Depression Inventory for All Subjects [ Time Frame: Baseline and 3 months ]
    The Beck Depression Inventory is a general measure of depression. There are 21 questions each with responses ranging from 0 (no issue or problem) to 3 (maximum issue/distress), all questions are related to emotions, mood, feelings, etc. The total possible score is 63 (higher scores represent more depression). The total score is calculated by adding the scores of the 21 items.

  4. Beck Anxiety Inventory Scores for All Subjects [ Time Frame: Baseline and 3 months ]
    The Beck Anxiety Inventory is a general measure of anxiety. There are 21 questions each with responses ranging from 0 (no issue or problem) to 3 (severe - I could barely stand it), all questions are related to the presence of signs or symptoms of anxiety. The total possible score is 63 and a higher score represents greater anxiety. The total score is calculated by adding the responses for each of the 21 items.

  5. Mini Mental State Examination (MMSE) Scores for All Subjects [ Time Frame: Baseline and 3 months ]
    The MMSE is a general measure of cognition (i.e., measures attention, memory, visuospatial construction, etc). It has 30 items, each item representing 1 point. The total score ranges from 0-30 with 30 being a perfect score (no cognitive impairment) and 0 being the lowest score (greatest possible level of impairment). The total score is calculated by adding the scores of each item.



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00443872


Locations
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United States, California
University of California - Irvine
Irvine, California, United States, 92697
Coastal Neurological Medical Group, Inc
La Jolla, California, United States, 92037
University of Southern California
Los Angeles, California, United States, 90093
The Parkinson's Institute
Sunnyvale, California, United States, 94085
United States, Florida
Parkinson's Disease and Movement Disorder Center of Boca Raton
Boca Raton, Florida, United States, 33486
University of South Florida
Tampa, Florida, United States, 33606
United States, Iowa
Methodist Plaza Speciality Clinic
Des Moines, Iowa, United States, 50309
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Louisiana
Ochsner Clinic Foundation
New Orleans, Louisiana, United States, 70121
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Harvard Vanguard Medical Associates
Boston, Massachusetts, United States, 02215
United States, Michigan
Henry Ford Health Center - Franklin Pointe
Southfield, Michigan, United States, 48034
United States, Minnesota
Struthers Parkinson's Center
Golden Valley, Minnesota, United States, 55427
United States, Ohio
University of Toledo
Toledo, Ohio, United States, 43614
United States, Rhode Island
NeuroHealth Parkinson Disease and Movement Disorder Center
Warwick, Rhode Island, United States, 02886
United States, Texas
Neurology Specialists Dallas
Dallas, Texas, United States, 75231
ETMC Neurological Institute
Tyler, Texas, United States, 75701
Sponsors and Collaborators
Parkinson's Disease and Movement Disorder Center of Boca Raton
Bausch Health Americas, Inc.
Investigators
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Principal Investigator: Rajesh Pahwa, MD University of Kansas Medical Center

Publications of Results:
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Responsible Party: Stuart Isaacson, MD, Director of the Parkinson's Disease and Movement Disorder Center of Boca Raton, Parkinson's Disease and Movement Disorder Center of Boca Raton
ClinicalTrials.gov Identifier: NCT00443872     History of Changes
Other Study ID Numbers: VAL-1.0-IV
First Posted: March 6, 2007    Key Record Dates
Results First Posted: October 31, 2014
Last Update Posted: October 31, 2014
Last Verified: October 2014
Keywords provided by Stuart Isaacson, Parkinson's Disease and Movement Disorder Center of Boca Raton:
Parkinson's disease
Dopamine agonist adverse effects
MAO-B inhibitor
orally disintegrating selegiline
Zelapar
Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Dopamine
Selegiline
Dopamine Agonists
Cardiotonic Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Protective Agents
Antidepressive Agents
Psychotropic Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Monoamine Oxidase Inhibitors
Enzyme Inhibitors
Neuroprotective Agents