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Tolerability and Efficacy of Switch From Oral Selegiline to Orally Disintegrating Selegiline (Zelapar) in Patients With Parkinson's Disease

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ClinicalTrials.gov Identifier: NCT00640159
Recruitment Status : Completed
First Posted : March 21, 2008
Last Update Posted : March 16, 2009
Sponsor:
Information provided by:
Baylor College of Medicine

Tracking Information
First Submitted Date  ICMJE March 18, 2008
First Posted Date  ICMJE March 21, 2008
Last Update Posted Date March 16, 2009
Study Start Date  ICMJE January 2007
Actual Primary Completion Date June 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 20, 2008)
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. [ Time Frame: Baseline to End-of-study ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00640159 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2008)
The secondary endpoints will include changes in the UPDRS, PDQ-8, BDI, FSS, ESS, ratings of global improvement and change in dyskinesia. [ Time Frame: Baseline to end-of-study ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Tolerability and Efficacy of Switch From Oral Selegiline to Orally Disintegrating Selegiline (Zelapar) in Patients With Parkinson's Disease
Official Title  ICMJE Tolerability and Efficacy of Switch From Oral Selegiline to Orally Disintegrating Selegiline (Zelapar) in Patients With Parkinson's Disease.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Parkinson's Disease
Intervention  ICMJE Drug: Zelapar
Switch from oral selegiline to Zelapar 1.25 mg QD titrated to 2.5 mg QD
Other Name: orally disintegrating selegiline
Study Arms  ICMJE Experimental: A
Open label switch from current oral selegiline dose to orally disintegrating selegiline (Zelapar) titrated to a dose of 2.5 mg QD.
Intervention: Drug: Zelapar
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: March 20, 2008)
55
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE August 2008
Actual Primary Completion Date June 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 90 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00640159
Other Study ID Numbers  ICMJE H-20709
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party William G. Ondo, MD, Baylor College of Medicine
Study Sponsor  ICMJE Baylor College of Medicine
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Baylor College of Medicine
Verification Date March 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP