Study of Azilect® (Rasagiline) in Levodopa-treated Parkinson's Disease Patients With Motor Fluctuations in Korea

• ClinicalTrials.gov Identifier: NCT01268891
• Recruitment Status: Completed
• First Posted: December 31, 2010
• Results First Posted: December 3, 2013
• Last Update Posted: December 3, 2013
• Sponsor: H. Lundbeck A/S
• Information provided by (Responsible Party): H. Lundbeck A/S

Study Description

Brief Summary:

To evaluate the efficacy of a fixed dose of Azilect® (1 mg/day) vs placebo as assessed by the change from baseline in mean total daily OFF time during 18 weeks of treatment in levodopa-treated Parkinson's Disease (PD) patients with motor fluctuations in Korea.

Condition or disease	Intervention/treatment	Phase
Parkinson's Disease	Drug: Placebo; Drug: Azilect®	Phase 3

Detailed Description:

Levodopa has been the mainstay therapy for PD for decades, and it is considered to be one of the most effective medications for relief of the symptoms of PD. However, within few months to few years the majority of levodopa-treated patients notice a decline in the duration of benefit of each dose and develop motor-complications. A major problem is the appearance of fluctuations in mobility, cycles of ON and OFF periods. The administration of Azilect®, a monoamine oxidase type B (MAO-B) inhibitor, can slow the elimination of the endogenous dopamine supplies or the dopamine produced from the exogenous levodopa therapy and may therefore improve ON-OFF fluctuations. Azilect® is approved for treatment of PD in Europe and the US.

The objective of this study is to evaluate the efficacy, tolerability, and safety of Azilect® compared to placebo in Korean PD patients with motor fluctuations on levodopa therapy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomised, Double-blind, Parallel-group, Placebo-controlled, Fixed-dose Study of [Azilect®] Rasagiline in Levodopa-treated Parkinson's Patients With Motor Fluctuations in Korea
• Study Start Date: January 2011
• Actual Primary Completion Date: June 2012

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo	Drug: Placebo; Once daily; tablet; orally; 18 weeks
Experimental: Azilect®	Drug: Azilect®; 1 mg daily; tablet; orally; 18 weeks; Other Name: Rasagiline

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline in Mean Total Daily OFF Time Using Parkinson's Disease Patient Diary [ Time Frame: Baseline and Weeks 6, 10, 14, and 18 ]

   Parkinson's Disease Patient Diary is a self-administered diary designed to assess motor fluctuations throughout the day. It is divided into 30-minute intervals, and the patient selects one of four options for each interval: asleep; off; on with no dyskinesia or without troublesome dyskinesia; or on with troublesome dyskinesia.

   The Change From Baseline in Mean Total Daily OFF Time is calculated by taking the difference between the average of the total daily OFF time at Weeks 6, 10, 14 and 18, and the Baseline Total Daily OFF Time.

Secondary Outcome Measures :

1. Clinical Status Using CGI-I Score During ON Time [ Time Frame: Week 18 ]
   Clinical Global Impression - Global Improvement (CGI-I) is a single-item rating scale used to evaluate a patient's condition relative to baseline on a 7-point scale, regardless of whether the improvement is related to the investigational medicinal product (IMP). The scale ranges from 1 (very much improved) to 7 (very much worse).
2. Change From Baseline in UPDRS-ADL Score During OFF Time [ Time Frame: Baseline and Week 18 ]
   Unified Parkinson's Disease Rating Scale (UPDRS) is a 42-item rating scale designed to assess Parkinson's Disease-related disability and impairment using a patient interview and a physical examination. It has 4 parts and 4 subsection scores. A higher score indicates a worst outcome. I: mentation, behaviour and mood symptoms - 0 to 16; II: activities of daily living (ADL) - 0 to 52; III: motor function - 0 to 108; IV: complications of dopaminergic therapy - 0 to 23. Subsection scores for I to III are used to calculate a total score that ranges from 0 (no disability) to 176 (total dependence).
3. Change From Baseline in UPDRS Motor Score During ON Time [ Time Frame: Baseline and Week 18 ]
   UPDRS is a 42-item rating scale designed to assess Parkinson's Disease-related disability and impairment using a patient interview and a physical examination. It has 4 parts and 4 subsection scores. A higher score indicates a worst outcome. I: mentation, behaviour and mood symptoms - 0 to 16; II: ADL - 0 to 52; III: motor function - 0 to 108; IV: complications of dopaminergic therapy - 0 to 23. Subsection scores for I to III are used to calculate a total score that ranges from 0 (no disability) to 176 (total dependence).

Eligibility Criteria

• Ages Eligible for Study: 30 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients with idiopathic PD
• Patients with motor fluctuations averaging at least 1 hour daily in the OFF state during the waking hours (not including morning akinesia)
• Patients with a Modified Hoehn and Yahr stage <5 in the OFF state
• Patients taking optimised levodopa/DOPA decarboxylase inhibitor (DDI) therapy for at least 14 days prior to baseline
• Patients receiving at least 3 daily doses of levodopa, not including a bedtime dose, and not more than 8 daily doses of levodopa
• Patient who have demonstrated the ability to keep accurate 24-hour diaries prior to randomisation

Exclusion Criteria:

• Patients with a clinically significant or unstable medical or surgical condition that would preclude his/her safe and complete study participation
• Patients taking any disallowed medication according to the Azilect® approved label
• Patients taking MAO inhibitors within 3 months prior to baseline visit
• Patients with a known serious adverse reaction to selegiline
• Patients with a clinically significant psychiatric illness, including a major depression, which compromises their ability to provide consent or participate fully in the study
• Patients with a Mini Mental State Examination (MMSE) score <=24
• Patients with a diagnosis of melanoma or a history of melanoma, or a suspicious lesion

Contacts and Locations

Sponsors and Collaborators

H. Lundbeck A/S

Investigators

• Study Director: Email contact via H. Lundbeck A/S; LundbeckClinicalTrials@lundbeck.com

More Information

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT01268891
• Other Study ID Numbers: 13484A
• First Posted: December 31, 2010
• Results First Posted: December 3, 2013
• Last Update Posted: December 3, 2013
• Last Verified: October 2013

Keywords provided by H. Lundbeck A/S:

Azilect; Motor fluctuations; Parkinson´s Disease; Rasagiline

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Rasagiline; Monoamine Oxidase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Neuroprotective Agents; Protective Agents; Physiological Effects of Drugs