Selegiline to Zelapar Switch Study in Parkinson Disease Patients
Primary Purpose
Parkinson's Disease
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Zelapar
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson's Disease focused on measuring Parkinson's disease, selegiline to Zelapar switch, orally disintegrating formulation
Eligibility Criteria
Inclusion Criteria:
- Idiopathic 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 and oral selegiline (5-10 mg /day), stable for at least 1 month and well tolerated
- Positive treatment response to current anti-parkinsonian medications in the opinion of the investigator
- 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 on any medications contraindicated with Zelapar (including meperidine/Demerol, tramadol, methadone, propoxyphene, dextromethorphan, other selegiline products)
- Patients with a known hypersensitivity to any formulation of selegiline or any of the inactive ingredients of Zelapar, or previous exposure to orally disintegrating selegiline
- History of melanoma
- Unstable/uncontrolled medical problems
- History of drug/alcohol abuse
- Patients currently taking rasagiline
Sites / Locations
- Dee Silver, MD at Coastal Neurological Medical Group, Inc
- James Tetrud, MD at The Parkinson's Institute
- Stuart Isaacson, MD at Parkinson's Disease and Movement Disorder Center of Boca Raton
- R. Malcolm Stewart, MD at Neurology Specialists of Dallas
- PDCMDC 6550 Fannin, Suite 1801
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Selegiline
Arm Description
Open label switch from current oral selegiline dose to orally disintegrating selegiline (Zelapar) titrated to a dose of 2.5 mg QD.
Outcomes
Primary Outcome Measures
Clinical Global Impression Scale
Baseline assessments included a clinical global impression scale. This is compared to day 40 assessment. The clinical global impression scale consists of a 3-item observer-rated scale that measures illness severity, global improvement or change and therapeutic response. Each item is rated between 1-7. The minimum score is 3. The maximum score is 21. A score of 3 means the patient's symptoms are very much improved. A score of 21 means the patient is very much worse.
Secondary Outcome Measures
MDS-UPDRS Scale at Baseline and Day 40
Baseline assessment include The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). This is compared to day 40 assessment. The MDS-UPDRS consist of 65 items. Each item can be rated between 0-4. The minimum sore is Zero. Zero means the patient is absent of Parkinson's disease symptoms. The maximum score is 260. 260 means the patient has severe Parkinson's disease symptoms.
Full Information
NCT ID
NCT00640159
First Posted
March 18, 2008
Last Updated
August 7, 2023
Sponsor
Baylor College of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT00640159
Brief Title
Selegiline to Zelapar Switch Study in Parkinson Disease Patients
Official Title
Tolerability and Efficacy of Switch From Oral Selegiline to Orally Disintegrating Selegiline (Zelapar) in Patients With Parkinson's Disease.
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
June 2008 (Actual)
Study Completion Date
August 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Baylor College of Medicine
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Parkinson's disease (PD) is a progressive neurodegenerative disease. Symptomatic therapy is primarily aimed at restoring dopamine function in the brain. Oral selegiline in conjunction with L-dopa has been a mainstay of therapy for PD patients experiencing motor fluctuations for many years. The mechanisms accounting for selegiline's beneficial adjunctive action in the treatment of PD are not fully understood. Inhibition of monoamine oxidase (MAO) type B (MAO-B) activity is generally considered to be of primary importance.
Oral selegiline has low bio-availability and is typically dosed BID, for a total of 5-10 mg daily. Recently, the FDA approved a new orally disintegration tablet (ODT) formulation of selegiline, called ZelaparTM. This new formulation utilizes Zydis technology to dissolve in the mouth, with absorption through the oral mucosa, thereby largely bypassing the gut and avoiding first pass hepatic metabolism. This allows more active drug to be delivered at a lower dose. Consequently, Zelapar is dosed once-daily, up to 2.5 mg per day. There are no empirical data indicating whether the use of the new approved formulation of selegiline ODT (Zelapar) is superior or preferred by patients compared to traditional oral selegiline. It is believed that clinical efficacy will be preserved or enhanced, by delivering more active drug, with improved patient preference for the ODT formulation due to the once-daily dosing .
The effectiveness of orally disintegrating selegiline as an adjunct to carbidopa/levodopa in the treatment of PD was established in a multicenter randomized placebo-controlled trial (n=140; 94 received orally disintegrating selegiline, 46 received placebo) of three months' duration. Patients randomized to orally disintegrating selegiline received a daily dose of 1.25 mg for the first 6 weeks and a daily dose of 2.5 mg for the last 6 weeks. Patients were all treated with levodopa and could additionally have been on dopamine agonists, anticholinergics, amantadine, or any combination of these during the trial. At 12 weeks, orally disintegrating selegiline-treated patients had an average of 2.2 hours per day less "OFF" time compared to baseline. Placebo treated patients had 0.6 hours per day less "OFF" time compared to baseline. These differences were significant (p < 0.001). Adverse events were very similar between drug and placebo.
Detailed Description
This is an open label, multicenter, 6 week study of the conversion from oral selegiline to orally disintegrating selegiline in PD patients with or without motor fluctuations, and currently taking levodopa. The study consists of the substitution of the oral selegiline with 1.25 mg of orally disintegrating selegiline for 10 days, and up titration of orally disintegrating selegiline to 2.5 mg per day for the next 30 days. The study will consist of 2 study visits in the clinic: Baseline and Day 40, and a telephone visit at Day 10.
Inclusion Criteria:
1. Idiopathic PD confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity 2. Male or female outpatients 3. Age 30-90 years 4. Current use of levodopa and oral selegiline (5-10 mg /day), stable for at least 1 month and well tolerated 5. Positive treatment response to current anti-parkinsonian medications in the opinion of the investigator 6. Acceptable contraception for females of child bearing potential 7. Willing and able to comply with study procedures. 8. Willing and able to give written informed consent prior to beginning any study procedures.
Exclusion Criteria:
1. Atypical parkinsonism due to drugs, metabolic disorders, encephalitis, trauma, or other neurodegenerative diseases. 2. 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. 3. Participation in another clinical drug trial within the previous four weeks. 4. Patients on any medications contraindicated with Zelapar (including meperidine/Demerol, tramadol, methadone, propoxyphene, dextromethorphan, other selegiline products) 5. Patients with a known hypersensitivity to any formulation of selegiline or any of the inactive ingredients of Zelapar, or previous exposure to orally disintegrating selegiline 6. History of melanoma 7. Unstable/uncontrolled medical problems 8. History of drug/alcohol abuse 9. Patients currently taking rasagiline
The primary efficacy point is number of subjects who prefer Zydis selegiline vs. the number who prefer oral selegiline, or have no preference. Descriptive statistics will be used to present the percentages of persons and adverse event resolutions. The secondary endpoints will include changes in the UPDRS, PDQ-8, BDI, FSS, ESS, ratings of global improvement and change in dyskinesia from Baseline to the Day 40 visit. Appropriate parametric (t-tests) and non-parametric analyses (Wilcoxon signed rank comparisons) will be conducted based on the scale being analyzed. An intent to treat approach will be used in which all subjects receiving at least one dose of study medication will be included in the analyses.
Tolerability and efficacy of switching from oral selegiline to Zydis selegiline in patients with Parkinson's disease.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Disease
Keywords
Parkinson's disease, selegiline to Zelapar switch, orally disintegrating formulation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Selegiline
Arm Type
Experimental
Arm Description
Open label switch from current oral selegiline dose to orally disintegrating selegiline (Zelapar) titrated to a dose of 2.5 mg QD.
Intervention Type
Drug
Intervention Name(s)
Zelapar
Other Intervention Name(s)
orally disintegrating selegiline
Intervention Description
Switch from oral selegiline to Zelapar 1.25 mg QD titrated to 2.5 mg QD
Primary Outcome Measure Information:
Title
Clinical Global Impression Scale
Description
Baseline assessments included a clinical global impression scale. This is compared to day 40 assessment. The clinical global impression scale consists of a 3-item observer-rated scale that measures illness severity, global improvement or change and therapeutic response. Each item is rated between 1-7. The minimum score is 3. The maximum score is 21. A score of 3 means the patient's symptoms are very much improved. A score of 21 means the patient is very much worse.
Time Frame
baseline versus 40 days
Secondary Outcome Measure Information:
Title
MDS-UPDRS Scale at Baseline and Day 40
Description
Baseline assessment include The Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). This is compared to day 40 assessment. The MDS-UPDRS consist of 65 items. Each item can be rated between 0-4. The minimum sore is Zero. Zero means the patient is absent of Parkinson's disease symptoms. The maximum score is 260. 260 means the patient has severe Parkinson's disease symptoms.
Time Frame
baseline versus day 40
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Idiopathic 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 and oral selegiline (5-10 mg /day), stable for at least 1 month and well tolerated
Positive treatment response to current anti-parkinsonian medications in the opinion of the investigator
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 on any medications contraindicated with Zelapar (including meperidine/Demerol, tramadol, methadone, propoxyphene, dextromethorphan, other selegiline products)
Patients with a known hypersensitivity to any formulation of selegiline or any of the inactive ingredients of Zelapar, or previous exposure to orally disintegrating selegiline
History of melanoma
Unstable/uncontrolled medical problems
History of drug/alcohol abuse
Patients currently taking rasagiline
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Greg Kricorian, MD
Organizational Affiliation
Valeant Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Dee Silver, MD at Coastal Neurological Medical Group, Inc
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
James Tetrud, MD at The Parkinson's Institute
City
Sunnyvale
State/Province
California
ZIP/Postal Code
94085
Country
United States
Facility Name
Stuart Isaacson, MD at Parkinson's Disease and Movement Disorder Center of Boca Raton
City
Boca Raton
State/Province
Florida
ZIP/Postal Code
33486
Country
United States
Facility Name
R. Malcolm Stewart, MD at Neurology Specialists of Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
PDCMDC 6550 Fannin, Suite 1801
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
21084213
Citation
Ondo WG, Hunter C, Isaacson SH, Silver DE, Stewart RM, Tetrud JW, Davidson A. Tolerability and efficacy of switching from oral selegiline to Zydis selegiline in patients with Parkinson's disease. Parkinsonism Relat Disord. 2011 Feb;17(2):117-8. doi: 10.1016/j.parkreldis.2010.10.001. Epub 2010 Nov 16.
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Selegiline to Zelapar Switch Study in Parkinson Disease Patients
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