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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

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Parkinson's Disease
Intervention Drug: orally disintegrating selegiline (Zelapar)
Enrollment 77
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title PD Patients With DA Related AE
Hide Arm/Group Description This is a one arm open label study of PD patients with a DA related AE
Period Title: Overall Study
Started 77
Completed 60
Not Completed 17
Reason Not Completed
Protocol Violation             7
Lost to Follow-up             2
Adverse Event             8
Arm/Group Title PD Patients With DA Related AE
Hide Arm/Group Description This is a one arm open label study of PD patients with a DA related AE
Overall Number of Baseline Participants 77
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants
<=18 years
0
   0.0%
Between 18 and 65 years
31
  40.3%
>=65 years
46
  59.7%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 77 participants
66.9  (8.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 77 participants
Female
38
  49.4%
Male
39
  50.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 77 participants
77
1.Primary Outcome
Title Percentage of Participants With Reduction in Adverse Events
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title PD Patients With DA Related AE
Hide Arm/Group Description:
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.
Overall Number of Participants Analyzed 60
Measure Type: Number
Unit of Measure: percentage of participants
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
2.Primary Outcome
Title Epworth Sleepiness Scale Score for Those With Daytime Sleepiness
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Based only on the number of patients with excessive daytime sleepiness at baseline
Arm/Group Title PD Patients With DA Related AE (Daytime Sleepiness)
Hide Arm/Group Description:
Patients who are experiencing a dopamine agonist (DA) related adverse effect (AE) of daytime sleepiness received 1.25 mg once daily of orally disintegrating selegiline for 6 weeks with an increase to 2.5 mg once daily orally disintegrating selegiline for the remaining 6 weeks if tolerated.
Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 13.5  (3.0)
3 months (12 weeks) 9.0  (3.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PD Patients With DA Related AE (Daytime Sleepiness)
Comments Comparison of mean group scores at baseline and 12 weeks
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.5
Parameter Dispersion
Type: Standard Deviation
Value: 1
Estimation Comments [Not Specified]
3.Primary Outcome
Title Neuropsychiatric Inventory (NPI) Hallucinations Scale Score for Those With Hallucinations
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who reported hallucinations at baseline
Arm/Group Title PD Patients With DA Related AE (Hallucinations)
Hide Arm/Group Description:
Patients who are experiencing the dopamine agonist (DA) related adverse effect of hallucinations. The participants received 1.25 mg once daily of orally disintegrating selegiline for 6 weeks after which it was increased to 2.5 mg once daily if tolerated.
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 3.3  (2.7)
3 months (12 weeks) 1.3  (1.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PD Patients With DA Related AE (Hallucinations)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.0
Estimation Comments [Not Specified]
4.Primary Outcome
Title Circumference of Lower Leg/Foot at Greatest Point of Swelling for Pedal Edema
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
Presence of pedal edema at baseline
Arm/Group Title PD Patiens With DA Related AE (Pedal Edema)
Hide Arm/Group Description:
Patients who are experiencing a dopamine agonist (DA) related AE of pedal edema received 1.25mg once daily of orally disintegrating selegiline for 6 weeks after which there was an increase to 2.5 mg once daily if tolerated.
Overall Number of Participants Analyzed 26
Mean (Standard Deviation)
Unit of Measure: centimeters
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)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PD Patiens With DA Related AE (Pedal Edema)
Comments Change in pedal edema as measured by change in lower leg/ankle circumference in the left and right legs
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.2
Estimation Comments Comparison of baseline vs. 3 month circumference of the Left and Right lower leg/ankle (change identical for both legs).
5.Primary Outcome
Title Barratt Impulsiveness Scale Score for Those With Impulsive Behavior
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
The number with ICDs at baseline
Arm/Group Title PD Patients With DA Related AE (Impulse Control Disorder)
Hide Arm/Group Description:
Patients who are experiencing dopamine agonist (DA) related adverse effect (AE) of impulse control disorder (ICD) received 1.25 mg once daily of orally disintegrating selegiline for 6 weeks after which it was increased to 2.5mg once daily if tolerated.
Overall Number of Participants Analyzed 25
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 64.1  (11.4)
3 months (12 weeks) 61.3  (12.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection PD Patients With DA Related AE (Impulse Control Disorder)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.8
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Unified Parkinson's Disease Rating Scale (UPDRS) Scores
Hide Description

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
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects completing the study were included
Arm/Group Title All Subjects With DA Related AEs (UPDRS Data)
Hide Arm/Group Description:
For all completed subjects (60) UPDRS activities of daily living scores and motor scores were collected. All patients received 1.25 mg once daily orally disintegrating selegiline for 6 weeks which was increased to 2.5mg once daily at 12 weeks if tolerated.
Overall Number of Participants Analyzed 60
Mean (Standard Deviation)
Unit of Measure: units on a scale
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)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Subjects With DA Related AEs (UPDRS Data)
Comments This analysis is for the Activities of Daily Living (ADL) section of the scale
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.6
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection All Subjects With DA Related AEs (UPDRS Data)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments This analysis is for the motor section of the UPDRS
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 2.2
Estimation Comments [Not Specified]
7.Secondary Outcome
Title PDQ-39 Quality of Life Assessment Total Scores
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title All Subjects PDQ-39
Hide Arm/Group Description:
This includes all patients in the study. They all received 1.25 mg once daily of orally disintegrating selegiline for 6 weeks which was increased to 2.5 mg once daily if tolerated.
Overall Number of Participants Analyzed 60
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 28.6  (15.3)
3 months (12 weeks) 24.4  (15.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All Subjects PDQ-39
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 4.2
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Beck Depression Inventory for All Subjects
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All
Arm/Group Title All PD Patients With DA Related AEs (BDI)
Hide Arm/Group Description:
All patients had a DA related AE and received 1.25 mg once daily orally disintegrating selegiline which was increased after 6 weeks to 2.5mg once daily if tolerated.
Overall Number of Participants Analyzed 60
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 10.2  (6.4)
3 months (12 weeks) 9.4  (7.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All PD Patients With DA Related AEs (BDI)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.8
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Beck Anxiety Inventory Scores for All Subjects
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All
Arm/Group Title All PD Patients With DA Related AEs (BAI)
Hide Arm/Group Description:
All patients had a DA related AE and received 1.25 mg once daily orally disintegrating selegiline which was increased after 6 weeks to 2.5mg once daily if tolerated.
Overall Number of Participants Analyzed 60
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 11.5  (9.7)
3 months (12 weeks) 10.9  (10.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All PD Patients With DA Related AEs (BAI)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.6
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Mini Mental State Examination (MMSE) Scores for All Subjects
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
All
Arm/Group Title All PD Patients With DA Related AEs (MMSE)
Hide Arm/Group Description:
All patients had a DA related AE and received 1.25 mg once daily orally disintegrating selegiline which was increased after 6 weeks to 2.5mg once daily if tolerated.
Overall Number of Participants Analyzed 60
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 28.8  (1.6)
3 months (12 weeks) 29.2  (1.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection All PD Patients With DA Related AEs (MMSE)
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Estimation Comments [Not Specified]
Time Frame 12 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PD Patients With DA Related AE
Hide Arm/Group Description This is a one arm open label study of PD patients with a DA related AE
All-Cause Mortality
PD Patients With DA Related AE
Affected / at Risk (%)
Total   --/--    
Hide Serious Adverse Events
PD Patients With DA Related AE
Affected / at Risk (%) # Events
Total   0/77 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PD Patients With DA Related AE
Affected / at Risk (%) # Events
Total   57/77 (74.03%)    
Cardiac disorders   
orthostatic hypotension *  4/77 (5.19%)  4
Gastrointestinal disorders   
Nausea/vomiting *  11/77 (14.29%)  11
General disorders   
Increased body aches and pain *  6/77 (7.79%)  6
Increased insomnia *  5/77 (6.49%)  5
Nervous system disorders   
worsening of PD *  13/77 (16.88%)  13
Dyskinesia *  8/77 (10.39%)  8
Restless legs *  4/77 (5.19%)  4
Psychiatric disorders   
Increased anxiety *  4/77 (5.19%)  4
Increased depression *  4/77 (5.19%)  4
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Kelly Lyons
Organization: University of Kansas Medical Center
Phone: 9135887159
EMail: klyons@kumc.edu
Layout table for additonal information
Responsible Party: Stuart Isaacson, Parkinson's Disease and Movement Disorder Center of Boca Raton
ClinicalTrials.gov Identifier: NCT00443872    
Other Study ID Numbers: VAL-1.0-IV
First Submitted: March 3, 2007
First Posted: March 6, 2007
Results First Submitted: May 23, 2012
Results First Posted: October 31, 2014
Last Update Posted: October 31, 2014