Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT00640159 |
| Other study ID # |
H-20709 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
January 2007 |
| Est. completion date |
August 2008 |
Study information
| Verified date |
August 2023 |
| Source |
Baylor College of Medicine |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
