Trial Outcomes & Findings for Efficacy of Orally Disintegrating Selegiline in Parkinson's Patients Experiencing Adverse Effects With Dopamine Agonists (NCT NCT00443872)

NCT ID: NCT00443872

Last Updated: 2014-10-31

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 77 participants
• Primary outcome timeframe: 3 Months
• Results posted on: 2014-10-31

Participant Flow

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.

Excessive daytime sleepiness was defined by an Epworth Sleepiness Scale (ESS) score greater than 10; pedal edema was bothersome to the subject; hallucinations were bothersome, but insight was maintained; and impulse control disorders (ICDs) included behaviors not requiring immediate medical attention and not harmful to the patient or to others.

Participant milestones

Measure	PD Patients With DA Related AE This is a one arm open label study of PD patients with a DA related AE
Overall Study STARTED	77
Overall Study COMPLETED	60
Overall Study NOT COMPLETED	17

Reasons for withdrawal

Measure	PD Patients With DA Related AE This is a one arm open label study of PD patients with a DA related AE
Overall Study Protocol Violation	7
Overall Study Lost to Follow-up	2
Overall Study Adverse Event	8

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	PD Patients With DA Related AE n=77 Participants This is a one arm open label study of PD patients with a DA related AE
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=5 Participants
Age, Categorical >=65 years	46 Participants n=5 Participants
Age, Continuous	66.9 years STANDARD_DEVIATION 8.6 • n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants
Region of Enrollment United States	77 participants n=5 Participants

PRIMARY outcome

Timeframe: 3 Months

Population: 77 patients enrolled in the study and 60 completed. Each patient had to have at least one of the following DA related AEs, excessive daytime sleepiness, hallucinations, pedal edema or impulse control disorder (they could have more than one AE). 60 subjects were selected based on results of previous studies (discontinued patients were replaced).

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.

Outcome measures

Measure	PD Patients With DA Related AE n=60 Participants Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder, received 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 Hallucinations (n=15)	86 percentage of participants
Percentage of Participants With Reduction in Adverse Events Pedal Edema (n=26)	73 percentage of participants
Percentage of Participants With Reduction in Adverse Events Excessive Daytime Sleepiness (n=50)	94 percentage of participants
Percentage of Participants With Reduction in Adverse Events Impulse Control Disorder (n=25)	84 percentage of participants
Percentage of Participants With Reduction in Adverse Events Any Adverse Event (n=60)	100 percentage of participants

PRIMARY outcome

Timeframe: Baseline and 3 months

Population: Based only on the number of patients with excessive daytime sleepiness at baseline

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.

Outcome measures

Measure	PD Patients With DA Related AE n=50 Participants Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder, received 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.
Epworth Sleepiness Scale Score for Those With Daytime Sleepiness Baseline	13.5 units on a scale Standard Deviation 3.0
Epworth Sleepiness Scale Score for Those With Daytime Sleepiness 3 months (12 weeks)	9.0 units on a scale Standard Deviation 3.7

PRIMARY outcome

Timeframe: Baseline and 3 months

Population: Patients who reported hallucinations at baseline

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.

Outcome measures

Measure	PD Patients With DA Related AE n=15 Participants Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder, received 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.
Neuropsychiatric Inventory (NPI) Hallucinations Scale Score for Those With Hallucinations Baseline	3.3 units on a scale Standard Deviation 2.7
Neuropsychiatric Inventory (NPI) Hallucinations Scale Score for Those With Hallucinations 3 months (12 weeks)	1.3 units on a scale Standard Deviation 1.8

PRIMARY outcome

Timeframe: Baseline and 3 months

Population: Presence of pedal edema at baseline

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.

Outcome measures

Measure	PD Patients With DA Related AE n=26 Participants Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder, received 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.
Circumference of Lower Leg/Foot at Greatest Point of Swelling for Pedal Edema Left foot baseline	25.8 centimeters Standard Deviation 3.4
Circumference of Lower Leg/Foot at Greatest Point of Swelling for Pedal Edema Left foot 3 months (12 weeks)	24.6 centimeters Standard Deviation 3.1
Circumference of Lower Leg/Foot at Greatest Point of Swelling for Pedal Edema Right foot baseline	26.4 centimeters Standard Deviation 4.2
Circumference of Lower Leg/Foot at Greatest Point of Swelling for Pedal Edema Right Foot 3 months (12 weeks)	25.2 centimeters Standard Deviation 4.0

PRIMARY outcome

Timeframe: Baseline and 3 months

Population: The number with ICDs at baseline

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.

Outcome measures

Measure	PD Patients With DA Related AE n=25 Participants Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder, received 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.
Barratt Impulsiveness Scale Score for Those With Impulsive Behavior Baseline	64.1 units on a scale Standard Deviation 11.4
Barratt Impulsiveness Scale Score for Those With Impulsive Behavior 3 months (12 weeks)	61.3 units on a scale Standard Deviation 12.4

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: All subjects completing the study were included

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.

Outcome measures

Measure	PD Patients With DA Related AE n=60 Participants Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder, received 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.
Unified Parkinson's Disease Rating Scale (UPDRS) Scores ADLs 3 months (12 weeks)	10.3 units on a scale Standard Deviation 5.1
Unified Parkinson's Disease Rating Scale (UPDRS) Scores Motor baseline	23.6 units on a scale Standard Deviation 10.9
Unified Parkinson's Disease Rating Scale (UPDRS) Scores ADLs baseline	11.9 units on a scale Standard Deviation 5.8
Unified Parkinson's Disease Rating Scale (UPDRS) Scores Motor 3 months (12 weeks)	21.4 units on a scale Standard Deviation 10.4

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	PD Patients With DA Related AE n=60 Participants Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder, received 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.
PDQ-39 Quality of Life Assessment Total Scores Baseline	28.6 units on a scale Standard Deviation 15.3
PDQ-39 Quality of Life Assessment Total Scores 3 months (12 weeks)	24.4 units on a scale Standard Deviation 15.1

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: All

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.

Outcome measures

Measure	PD Patients With DA Related AE n=60 Participants Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder, received 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.
Beck Depression Inventory for All Subjects 3 months (12 weeks)	9.4 units on a scale Standard Deviation 7.4
Beck Depression Inventory for All Subjects Baseline	10.2 units on a scale Standard Deviation 6.4

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: All

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.

Outcome measures

Measure	PD Patients With DA Related AE n=60 Participants Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder, received 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.
Beck Anxiety Inventory Scores for All Subjects Baseline	11.5 units on a scale Standard Deviation 9.7
Beck Anxiety Inventory Scores for All Subjects 3 months (12 weeks)	10.9 units on a scale Standard Deviation 10.2

SECONDARY outcome

Timeframe: Baseline and 3 months

Population: All

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.

Outcome measures

Measure	PD Patients With DA Related AE n=60 Participants Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of either one or more of the following: excessive daytime sleepiness, hallucinations, pedal edema, impulse control disorder, received 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.
Mini Mental State Examination (MMSE) Scores for All Subjects Baseline	28.8 units on a scale Standard Deviation 1.6
Mini Mental State Examination (MMSE) Scores for All Subjects 3 months (12 weeks)	29.2 units on a scale Standard Deviation 1.2

Adverse Events

PD Patients With DA Related AE

Serious events: 0 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	PD Patients With DA Related AE n=77 participants at risk This is a one arm open label study of PD patients with a DA related AE
Nervous system disorders worsening of PD	16.9% 13/77 • Number of events 13 • 12 weeks
Gastrointestinal disorders Nausea/vomiting	14.3% 11/77 • Number of events 11 • 12 weeks
Nervous system disorders Dyskinesia	10.4% 8/77 • Number of events 8 • 12 weeks
General disorders Increased body aches and pain	7.8% 6/77 • Number of events 6 • 12 weeks
General disorders Increased insomnia	6.5% 5/77 • Number of events 5 • 12 weeks
Psychiatric disorders Increased anxiety	5.2% 4/77 • Number of events 4 • 12 weeks
Nervous system disorders Restless legs	5.2% 4/77 • Number of events 4 • 12 weeks
Cardiac disorders orthostatic hypotension	5.2% 4/77 • Number of events 4 • 12 weeks
Psychiatric disorders Increased depression	5.2% 4/77 • Number of events 4 • 12 weeks

Additional Information

Dr. Kelly Lyons

University of Kansas Medical Center

Phone: 9135887159

Email: klyons@kumc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place