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

• Sponsor: H. Lundbeck A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01268891
• Collaborator: (none)
• Enrollment: 132
• Arms: 2

Study Details

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
• 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: Jan 1, 2011
• Actual Primary Completion Date: Jun 1, 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 Names: Rasagiline

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Mean Total Daily OFF Time Using Parkinson's Disease Patient Diary [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 [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 [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 [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

Criteria

• Ages Eligible for Study: 30 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

No locations specified.

Sponsors and Collaborators

• H. Lundbeck A/S

Investigators

• Study Director: Email contact via H. Lundbeck A/S, [e-mail]

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: H. Lundbeck A/S
• ClinicalTrials.gov Identifier: NCT01268891
• Other Study ID Numbers: 13484A
• First Posted: Dec 31, 2010
• Last Update Posted: Dec 3, 2013
• Last Verified: Oct 1, 2013

• Keywords provided by H. Lundbeck A/S: Azilect; Motor fluctuations; Parkinson´s Disease; Rasagiline
• Additional relevant MeSH terms: Parkinson Disease; Rasagiline

Study Results

Participant Flow

Pre-assignment Detail	The study consisted of a 2-week Screening Period during which the levodopa dose was optimised (if required), a 2-week Screening Period during which the levodopa dose was stabilised, an 18-week double-blind treatment period with rasagiline or placebo once daily (patients were randomised in a 1:1 ratio), and a 4-week Safety Follow-up Period.

Arm/Group Title	Placebo	Azilect®
Arm/Group Description	Once daily; tablet; orally; 18 weeks	1 mg daily; tablet; orally; 18 weeks
Period Title: Overall Study
STARTED	66	66
COMPLETED	58	58
NOT COMPLETED	8	8

Baseline Characteristics

Arm/Group Title	Placebo	Azilect®	Total
Arm/Group Description	Once daily; tablet; orally; 18 weeks	1 mg daily; tablet; orally; 18 weeks	Total of all reporting groups
Overall Participants	66	66	132
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.5 (9.0)	60.2 (8.6)	59.8 (8.8)
Sex: Female, Male (Count of Participants)
Female	23 34.8%	33 50%	56 42.4%
Male	43 65.2%	33 50%	76 57.6%
Total Daily OFF Time (hours) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [hours]	6.24 (2.73)	6.26 (2.29)	6.25 (2.50)
CGI-S (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	3.05 (0.92)	2.94 (1.11)	2.99 (1.02)
UPDRS-ADL Score During OFF Time (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	11.15 (5.84)	11.79 (6.58)	11.48 (6.21)
UPDRS Motor Score During ON time (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	19.81 (8.39)	17.98 (8.71)	18.86 (8.57)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Full-analysis set (FAS); observed cases (OC)

Arm/Group Title	Placebo	Azilect®
Arm/Group Description	Once daily; tablet; orally; 18 weeks	1 mg daily; tablet; orally; 18 weeks
Measure Participants	59	63
Mean (Standard Error) [hours]	-1.24 (0.26)	-1.59 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Azilect®
	Comments	The power for this study, which is designed to show a trend, that is, to show a clinical difference in the primary outcome measure, is 72%.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3257
	Comments	The threshold for statistical significance in showing a trend for this study is 0.10.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 90%; -0.93 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.35
	Estimation Comments

2. Secondary Outcome

Title	Clinical Status Using CGI-I Score During ON Time
Description	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).
Time Frame	Week 18

Outcome Measure Data

Analysis Population Description

FAS; last observation carried forward (LOCF)

Arm/Group Title	Placebo	Azilect®
Arm/Group Description	Once daily; tablet; orally; 18 weeks	1 mg daily; tablet; orally; 18 weeks
Measure Participants	59	63
Mean (Standard Error) [units on a scale]	3.35 (0.13)	3.05 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Azilect®
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0946
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -0.65 to 0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.18
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in UPDRS-ADL Score During OFF Time
Description	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).
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

FAS; LOCF

Arm/Group Title	Placebo	Azilect®
Arm/Group Description	Once daily; tablet; orally; 18 weeks	1 mg daily; tablet; orally; 18 weeks
Measure Participants	59	63
Mean (Standard Error) [units on a scale]	0.13 (0.42)	-0.57 (0.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Azilect®
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2258
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.70
	Confidence Interval	(2-Sided) 95%; -1.84 to 0.44
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.57
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in UPDRS Motor Score During ON Time
Description	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).
Time Frame	Baseline and Week 18

Outcome Measure Data

Analysis Population Description

FAS; LOCF

Arm/Group Title	Placebo	Azilect®
Arm/Group Description	Once daily; tablet; orally; 18 weeks	1 mg daily; tablet; orally; 18 weeks
Measure Participants	59	63
Mean (Standard Error) [units on a scale]	-1.52 (0.72)	-2.87 (0.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Azilect®
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1700
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.35
	Confidence Interval	(2-Sided) 95%; -3.29 to 0.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.98
	Estimation Comments

Adverse Events

Time Frame	Serious Adverse Events: 18-week double-blind treatment period and 4-week safety follow-up period. Other Adverse Events: 18-week double-blind treatment period.
Arm/Group Title	Placebo		Azilect®
Arm/Group Description
All Cause Mortality
	Placebo		Azilect®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Azilect®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/66 (6.1%)		5/66 (7.6%)
Gastrointestinal disorders
Gastritis	0/66 (0%)		1/66 (1.5%)
Infections and infestations
Pyelonephritis acute	0/66 (0%)		1/66 (1.5%)
Injury, poisoning and procedural complications
Joint injury	1/66 (1.5%)		0/66 (0%)
Subdural haemorrhage	1/66 (1.5%)		0/66 (0%)
Wrist fracture	1/66 (1.5%)		0/66 (0%)
Musculoskeletal and connective tissue disorders
Neck pain	0/66 (0%)		1/66 (1.5%)
Osteoarthritis	1/66 (1.5%)		0/66 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Borderline ovarian tumour	0/23 (0%)		1/33 (3%)
Breast cancer	0/66 (0%)		1/66 (1.5%)
Nervous system disorders
Loss of consciousness	0/66 (0%)		1/66 (1.5%)
Subarachnoid haemorrhage	1/66 (1.5%)		0/66 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Azilect®
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/66 (18.2%)		19/66 (28.8%)
Injury, poisoning and procedural complications
Accidental overdose	5/66 (7.6%)		3/66 (4.5%)
Nervous system disorders
Dizziness	1/66 (1.5%)		4/66 (6.1%)
Dyskinesia	5/66 (7.6%)		8/66 (12.1%)
Psychiatric disorders
Insomnia	2/66 (3%)		4/66 (6.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/66 (0%)		4/66 (6.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The results of this study will be published at the discretion of H. Lundbeck A/S. H. Lundbeck A/S will ensure that the authorship of all publications based on this study is in accordance with the criteria defined by the International Committee of Medical Journal Editors (ICMJE). The primary publication must be published before any secondary publications.