Selegiline to Zelapar Switch Study in Parkinson Disease Patients

NCT00640159 | Completed Phase 4 Results

• 1 other identifier: H-20709
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 5

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.

Conditions

Parkinson's Disease

Keywords

Parkinson's disease; selegiline to Zelapar switch; orally disintegrating formulation

Outcome Measures

Primary Outcomes (1)

• 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.

  baseline versus 40 days

Secondary Outcomes (1)

• MDS-UPDRS Scale at Baseline and Day 40

  baseline versus day 40

Study Arms (1)

Selegiline

EXPERIMENTAL

Open label switch from current oral selegiline dose to orally disintegrating selegiline (Zelapar) titrated to a dose of 2.5 mg QD.

Drug: Zelapar

Interventions

Zelapar DRUG

Switch from oral selegiline to Zelapar 1.25 mg QD titrated to 2.5 mg QD

Also known as: orally disintegrating selegiline

Selegiline

Eligibility Criteria

• Age: 30 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (5)

Dee Silver, MD at Coastal Neurological Medical Group, Inc

La Jolla, California, 92037, United States

Location

James Tetrud, MD at The Parkinson's Institute

Sunnyvale, California, 94085, United States

Location

Stuart Isaacson, MD at Parkinson's Disease and Movement Disorder Center of Boca Raton

Boca Raton, Florida, 33486, United States

Location

R. Malcolm Stewart, MD at Neurology Specialists of Dallas

Dallas, Texas, 75231, United States

Location

PDCMDC 6550 Fannin, Suite 1801

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 21084213 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Interventions

Selegiline

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: William G. Ondo , MD
• Organization: Baylor College of Medicine/Houston Methodist

wondo@houstonmethodist.org

713-363-8930

Study Officials

• Greg Kricorian, MD

  Valeant Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 18, 2008
• First Posted: March 21, 2008
• Study Start: January 1, 2007
• Primary Completion: June 1, 2008
• Study Completion: August 1, 2008
• Last Updated: August 9, 2023
• Results First Posted: August 9, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)