A Phase 4 interventional study of orally disintegrating selegiline (Zelapar) in Parkinson's Disease, sponsored by Parkinson's Disease and Movement Disorder Center of Boca Raton. Completed at 17 sites in United States. Open to participants aged 30 Years to 90 Years. Per ClinicalTrials.gov, last updated 2014-10-31.
Sponsored by Parkinson's Disease and Movement Disorder Center of Boca Raton · Phase 4, Interventional, and Treatment
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.
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.
4,487 studies on the registry are indexed under Parkinson Disease; 1,082 are open to participants now.
This study's enrollment of 77 is above the median of 40 across 3,294 interventional studies indexed under Parkinson Disease.
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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.
Exclusion Criteria:
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
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline and 3 months
Unified Parkinson's Disease Rating Scale (UPDRS) Scores
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.
Time frame: Baseline and 3 months
PDQ-39 Quality of Life Assessment Total Scores
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.
Time frame: Baseline and 3 months
Beck Depression Inventory for All Subjects
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.
Time frame: Baseline and 3 months
Beck Anxiety Inventory Scores for All Subjects
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.
Time frame: Baseline and 3 months
Mini Mental State Examination (MMSE) Scores for All Subjects
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.
Time frame: Baseline and 3 months
Parkinson's disease (PD) patients with levodopa-induced motor fluctuations were enrolled at 12 sites in the United States. The first subject was enrolled in March 2007, and the last subject completed in September 2008.
| Milestone | PD Patients With DA Related AE |
|---|---|
| Started | 77 |
| Completed | 60 |
| Not completed | 17 |
| Withdrew: Protocol violation | 7 |
| Withdrew: Lost to follow-up | 2 |
| Withdrew: Adverse event | 8 |
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.
| percentage of participants | PD Patients With DA Related AE |
|---|---|
| Excessive Daytime Sleepiness (n=50) | 94 |
| Hallucinations (n=15) | 86 |
| Pedal Edema (n=26) | 73 |
| Impulse Control Disorder (n=25) | 84 |
| Any Adverse Event (n=60) | 100 |
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.
| units on a scale | PD Patients With DA Related AE (Daytime Sleepiness) |
|---|---|
| Baseline | 13.5 ± 3.0 |
| 3 months (12 weeks) | 9.0 ± 3.7 |
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.
| units on a scale | PD Patients With DA Related AE (Hallucinations) |
|---|---|
| Baseline | 3.3 ± 2.7 |
| 3 months (12 weeks) | 1.3 ± 1.8 |
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.
| centimeters | PD Patiens With DA Related AE (Pedal Edema) |
|---|---|
| Left foot baseline | 25.8 ± 3.4 |
| Left foot 3 months (12 weeks) | 24.6 ± 3.1 |
| Right foot baseline | 26.4 ± 4.2 |
| Right Foot 3 months (12 weeks) | 25.2 ± 4.0 |
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.
| units on a scale | PD Patients With DA Related AE (Impulse Control Disorder) |
|---|---|
| Baseline | 64.1 ± 11.4 |
| 3 months (12 weeks) | 61.3 ± 12.4 |
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.
| units on a scale | All Subjects With DA Related AEs (UPDRS Data) |
|---|---|
| ADLs baseline | 11.9 ± 5.8 |
| ADLs 3 months (12 weeks) | 10.3 ± 5.1 |
| Motor baseline | 23.6 ± 10.9 |
| Motor 3 months (12 weeks) | 21.4 ± 10.4 |
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.
| units on a scale | All Subjects PDQ-39 |
|---|---|
| Baseline | 28.6 ± 15.3 |
| 3 months (12 weeks) | 24.4 ± 15.1 |
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.
| units on a scale | All PD Patients With DA Related AEs (BDI) |
|---|---|
| Baseline | 10.2 ± 6.4 |
| 3 months (12 weeks) | 9.4 ± 7.4 |
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.
| units on a scale | All PD Patients With DA Related AEs (BAI) |
|---|---|
| Baseline | 11.5 ± 9.7 |
| 3 months (12 weeks) | 10.9 ± 10.2 |
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.
| units on a scale | All PD Patients With DA Related AEs (MMSE) |
|---|---|
| Baseline | 28.8 ± 1.6 |
| 3 months (12 weeks) | 29.2 ± 1.2 |
Collected over 12 weeks. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| PD Patients With DA Related AE | — | 0/77 (0%) | 57/77 (74%) |
| Event | PD Patients With DA Related AE |
|---|---|
| worsening of PDNervous system disorders | 13/77 |
| Nausea/vomitingGastrointestinal disorders | 11/77 |
| DyskinesiaNervous system disorders | 8/77 |
| Increased body aches and painGeneral disorders | 6/77 |
| Increased insomniaGeneral disorders | 5/77 |
| Increased anxietyPsychiatric disorders | 4/77 |
| Restless legsNervous system disorders | 4/77 |
| orthostatic hypotensionCardiac disorders | 4/77 |
| Increased depressionPsychiatric disorders | 4/77 |
| Age, Categorical(Participants) | PD Patients With DA Related AE |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 31 |
| >=65 years | 46 |
| Age, Continuous(years) | PD Patients With DA Related AE |
|---|---|
| Mean | 66.9 ± 8.6 |
| Sex: Female, Male(Participants) | PD Patients With DA Related AE |
|---|---|
| Female | 38 |
| Male | 39 |
| Region of Enrollment(participants) | PD Patients With DA Related AE |
|---|---|
| United States | 77 |
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