Parkinson's DiseasePhase 4NCT00640159
Selegiline to Zelapar Switch Study in Parkinson Disease Patients
A Phase 4 study testing Zelapar in people with Parkinson's Disease, run by Baylor College of Medicine at 5 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 30 to 90 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- Zelapar
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 5 sitesUnited States
- Study dates
- Jan 2007to Aug 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- Unstable/uncontrolled medical problems
- History of drug/alcohol abuse
- Patients currently taking rasagiline
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Stuart Isaacson, MD at Parkinson's Disease and Movement Disorder Center of Boca Raton
Boca Raton, Florida, 33486
R. Malcolm Stewart, MD at Neurology Specialists of Dallas
Dallas, Texas, 75231
PDCMDC 6550 Fannin, Suite 1801
Houston, Texas, 77030
Dee Silver, MD at Coastal Neurological Medical Group, Inc
La Jolla, California, 92037
James Tetrud, MD at The Parkinson's Institute
Sunnyvale, California, 94085
About this study
Official title: Tolerability and Efficacy of Switch From Oral Selegiline to Orally Disintegrating Selegiline (Zelapar) in Patients With Parkinson's Disease.
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.
Read the 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:
- 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:
- 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.
- Conditions
- Parkinson's Disease
- Being tested
- Zelapar
- Keywords
- Parkinson's disease, selegiline to Zelapar switch, orally disintegrating formulation
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZelaparDrug
Also called orally disintegrating selegiline
Switch from oral selegiline to Zelapar 1.25 mg QD titrated to 2.5 mg QD
| Study group | Role | What they receive |
|---|---|---|
| Selegiline | Experimental | Open label switch from current oral selegiline dose to orally disintegrating selegiline (Zelapar) titrated to a dose of 2.5 mg QD. Receives: Drug: Zelapar |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline versus 40 days
Secondary outcomes (1)
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.
Measured: baseline versus day 40
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Mar 2008 (estimated)
- Study startJan 2007
- Primary completionJun 2008
- Study completionAug 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joseph Jankovic, Baylor College of Medicine
- Investigators
- Greg Kricorian, MD, Study director, Valeant Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00640159
- Sponsor's protocol ID
- H-20709
- Status last verified
- Aug 2023
- First submitted
- 18 Mar 2008
- Last updated
- 9 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 21084213
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tolerability and Efficacy of Switch From Oral Selegiline to Orally Disintegrating Selegiline (Zelapar) in Patients With Parkinson's Disease.
- ClinicalTrials.gov ID
- NCT00640159
- Acronym / sponsor ID
- H-20709
- Conditions
- Parkinson's Disease
- Keywords
- Parkinson's disease, selegiline to Zelapar switch, orally disintegrating formulation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Study start
- Jan 2007
- Primary completion
- Jun 2008 (actual)
- Study completion
- Aug 2008 (actual)
- First posted
- 21 Mar 2008 (estimated)
- Results
- Posted 9 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Selegiline | Experimental | Drug: ZelaparOpen label switch from current oral selegiline dose to orally disintegrating selegiline (Zelapar) titrated to a dose of 2.5 mg QD. |
Who may qualify
- Ages
- 30 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZelaparAlso: orally disintegrating selegilineSwitch from oral selegiline to Zelapar 1.25 mg QD titrated to 2.5 mg QD | Drug | Selegiline |
Primary outcome
Clinical Global Impression Scale
Time frame: baseline versus 40 days
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.
1 secondary outcome
MDS-UPDRS Scale at Baseline and Day 40
Time frame: baseline versus day 40
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21084213Ondo 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Greg Kricorian, MD study director
Valeant Pharmaceuticals
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Zelapar in people with Parkinson's Disease, run by Baylor College of Medicine at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Global Impression Scale (time frame: baseline versus 40 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00640159, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2023.