Rasagiline in Early Parkinson's Disease Patients Not Treated With Levodopa in China

• Sponsor: H. Lundbeck A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01556165
• Collaborator: (none)
• Enrollment: 130
• Locations: 15
• Arms: 2
• Patients Per Site: 8.7

Study Details

Study Description

Brief Summary

Rasagiline has been developed for the treatment of Parkinson's Disease (PD), as monotherapy in early PD patients not treated with levodopa, and as adjunct therapy to levodopa in levodopa-treated PD patients with motor fluctuations.

The rationale for conducting this study is to evaluate the efficacy, tolerability, and safety of rasagiline compared to placebo in Chinese PD patients not treated with levodopa.

Condition or Disease	Intervention/Treatment	Phase
Parkinson's Disease	Drug: rasagiline; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 130 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 Rasagiline in Early Parkinson's Disease Patients Not Treated With Levodopa in China
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: rasagiline	Drug: rasagiline; 1 mg/day, tablets, once daily, orally; Other Names: Azilect
Placebo Comparator: placebo	Drug: placebo; tablets, once daily, orally

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 26 in UPDRS Total Score [Baseline to Week 26]

   The Unified Parkinson's Disease Rating Scale (UPDRS) is a 42-item rating scale designed to assess Parkinson's disease-related disability and impairment. The scale comprises four parts: Part I evaluates mentation, behaviour, and mood symptoms; Part II evaluates activities of daily living (ADL); Part III evaluates motor function; and Part IV evaluates complications of dopaminergic therapy. The total score is the sum of the subscale scores for Parts I to III and ranges from 0 (no disability) to 176 (total dependence).

Secondary Outcome Measures

1. Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part I) [Baseline to Week 26]

   The Unified Parkinson's Disease Rating Scale (UPDRS) Part I evaluates mentation, behaviour and mood symptoms, it comprises 4 parts and the score ranges from 0 (normal) to 16 (severe impairement)

2. Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part II) [Baseline to Week 26]

   The Unified Parkinson's Disease Rating Scale (UPDRS) Part II evaluates activities of daily living, it comprises 13 parts and the score ranges from 0 (normal) to 52 (severe impairement and disability)

3. Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part III) [Baseline to Week 26]

   The Unified Parkinson's Disease Rating Scale (UPDRS) Part III evaluates motor function, it comprises 14 parts and the score ranges from 0 (normal) to 108 (severe impairement and disability)

4. Time to Onset of Levodopa Therapy [Baseline to Week 26]

   It was stated in the statistical analysis plan (SAP) that if >10% of FAS patients were considered to have taken levodopa during the treatment period, the endpoint, time to onset of levodopa treatment was to be analysed. However, since only one patient (in the placebo group) had levodopa administered during the treatment period, this endpoint was not analysed, as had been defined a priori in the SAP.

5. Levodopa Administration Within 26 Weeks [Baseline to Week 26]

   It was stated in the statistical analysis plan (SAP) that if >10% of FAS patients were considered to have taken levodopa during the treatment period, the endpoint, levodopa administration within 26 Weeks was to be analysed. However, since only one patient (in the placebo group) had levodopa administered during the treatment period, this endpoint was not analysed, as had been defined a priori in the SAP.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with idiopathic PD.

• Patients with a Modified Hoehn and Yahr stage <3.

Exclusion Criteria:

• Patients with a clinically significant or unstable medical or surgical condition that would preclude his/her safe and complete study participation.

• Patients with a clinically significant or unstable vascular disease.

• 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.

Other inclusion and exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CN015	Beijing		China	100034
2	CN001	Beijing		China	100730
3	CN011	Chengdu		China	610041
4	CN003	Guangzhou		China	510120
5	CN005	Guangzhou		China	510180
6	CN017	Guangzhou		China	510260
7	CN004	Hangzhou		China	310009
8	CN012	Shanghai		China	200025
9	CN007	Shanghai		China	200040
10	CN013	Shanghai		China	200127
11	CN006	Suzhou		China	215004
12	CN009	Wuhan		China	430022
13	CN016	Wuhan		China	430030
14	CN010	Xi'an		China	710032
15	CN014	Xi'an		China	710061

Sponsors and Collaborators

• H. Lundbeck A/S

Investigators

• Principal Investigator: 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: NCT01556165
• Other Study ID Numbers: 13485A
• First Posted: Mar 16, 2012
• Last Update Posted: Dec 23, 2014
• Last Verified: Dec 1, 2014

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

Study Results

Participant Flow

Recruitment Details	Outpatients aged 35 years or older, who had idiopathic Parkinson's disease and were not treated with levodopa or other antiparkinsonian medications, were recruited for this study from China.
Pre-assignment Detail	A Screening Visit was held approximately 28 days prior to group assignment (group assignment was held during the Baseline Visit). Patients who met each of the inclusion criteria and none of the exclusion criteria were eligible to participate in this study.

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	placebo: tablets, once daily, orally	rasagiline: 1 mg/day, tablets, once daily, orally
Period Title: Overall Study
STARTED	65	65
COMPLETED	53	58
NOT COMPLETED	12	7

Baseline Characteristics

Arm/Group Title	Placebo	Rasagiline	Total
Arm/Group Description	placebo: tablets, once daily, orally	rasagiline: 1 mg/day, tablets, once daily, orally	Total of all reporting groups
Overall Participants	65	65	130
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.5 (9.22)	58.5 (8.72)	59.0 (8.95)
Sex: Female, Male (Count of Participants)
Female	25 38.5%	30 46.2%	55 42.3%
Male	40 61.5%	35 53.8%	75 57.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	65 100%	65 100%	130 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 26 in UPDRS Total Score
Description	The Unified Parkinson's Disease Rating Scale (UPDRS) is a 42-item rating scale designed to assess Parkinson's disease-related disability and impairment. The scale comprises four parts: Part I evaluates mentation, behaviour, and mood symptoms; Part II evaluates activities of daily living (ADL); Part III evaluates motor function; and Part IV evaluates complications of dopaminergic therapy. The total score is the sum of the subscale scores for Parts I to III and ranges from 0 (no disability) to 176 (total dependence).
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

The full-analysis set (FAS) comprised all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the primary efficacy variable.

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	placebo: tablets, once daily, orally	rasagiline: 1 mg/day, tablets, once daily, orally
Measure Participants	63	64
Mean (Standard Error) [units on a scale]	-0.18 (0.98)	-3.18 (0.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rasagiline
	Comments	This study was designed to show a trend, that is, to show a clinical difference in the primary efficacy analysis, at a two-sided significance level of 0.25. Assuming a difference between rasagiline and placebo of a 3-point change in the UPDRS total score and a standard deviation on the change from baseline of 7 points, a sample size of 60 patients per treatment group gave an 88% probability of showing a trend. LOCF (last observation carried forward) was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0254
	Comments	No adjustments for multiple comparisons were made.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.00
	Confidence Interval	(2-Sided) 75%; -4.53 to -1.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.32
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part I)
Description	The Unified Parkinson's Disease Rating Scale (UPDRS) Part I evaluates mentation, behaviour and mood symptoms, it comprises 4 parts and the score ranges from 0 (normal) to 16 (severe impairement)
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

The full-analysis set (FAS) comprised all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the primary efficacy variable.

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	placebo: tablets, once daily, orally	rasagiline: 1 mg/day, tablets, once daily, orally
Measure Participants	63	64
Mean (Standard Error) [units on a scale]	0.08 (0.15)	-0.54 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rasagiline
	Comments	LOCF (last observation carried forward) was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0032
	Comments
	Method	ANCOVA
	Comments	The same ANCOVA methodology as for the primary endpoint was used.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.62
	Confidence Interval	(2-Sided) 95%; -1.03 to -0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.21
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part II)
Description	The Unified Parkinson's Disease Rating Scale (UPDRS) Part II evaluates activities of daily living, it comprises 13 parts and the score ranges from 0 (normal) to 52 (severe impairement and disability)
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

The full-analysis set (FAS) comprised all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the primary efficacy variable.

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	placebo: tablets, once daily, orally	rasagiline: 1 mg/day, tablets, once daily, orally
Measure Participants	63	64
Mean (Standard Error) [units on a scale]	0.25 (0.38)	-0.43 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rasagiline
	Comments	LOCF (last observation carried forward) was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1963
	Comments
	Method	ANCOVA
	Comments	The same ANCOVA methodology as for the primary endpoint was used.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.67
	Confidence Interval	(2-Sided) 95%; -1.70 to 0.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.52
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to Week 26 in Subscale Scores of the UPDRS (Part III)
Description	The Unified Parkinson's Disease Rating Scale (UPDRS) Part III evaluates motor function, it comprises 14 parts and the score ranges from 0 (normal) to 108 (severe impairement and disability)
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

The full-analysis set (FAS) comprised all patients in the APTS who had a valid baseline assessment and at least one valid post-baseline assessment of the primary efficacy variable.

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	placebo: tablets, once daily, orally	rasagiline: 1 mg/day, tablets, once daily, orally
Measure Participants	63	64
Mean (Standard Error) [units on a scale]	-0.52 (0.68)	-2.23 (0.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Rasagiline
	Comments	LOCF (last observation carried forward) was used.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0641
	Comments
	Method	ANCOVA
	Comments	The same ANCOVA methodology as for the primary endpoint was used.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.71
	Confidence Interval	(2-Sided) 95%; -3.52 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.91
	Estimation Comments

5. Secondary Outcome

Title	Time to Onset of Levodopa Therapy
Description	It was stated in the statistical analysis plan (SAP) that if >10% of FAS patients were considered to have taken levodopa during the treatment period, the endpoint, time to onset of levodopa treatment was to be analysed. However, since only one patient (in the placebo group) had levodopa administered during the treatment period, this endpoint was not analysed, as had been defined a priori in the SAP.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Levodopa Administration Within 26 Weeks
Description	It was stated in the statistical analysis plan (SAP) that if >10% of FAS patients were considered to have taken levodopa during the treatment period, the endpoint, levodopa administration within 26 Weeks was to be analysed. However, since only one patient (in the placebo group) had levodopa administered during the treatment period, this endpoint was not analysed, as had been defined a priori in the SAP.
Time Frame	Baseline to Week 26

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	30 weeks
Arm/Group Title	Placebo		Rasagiline
Arm/Group Description	placebo: tablets, once daily, orally		rasagiline: 1 mg/day, tablets, once daily, orally
All Cause Mortality
	Placebo		Rasagiline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Rasagiline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/65 (6.2%)		0/65 (0%)
Eye disorders
Cataract	1/65 (1.5%)		0/65 (0%)
Injury, poisoning and procedural complications
Road traffic accident	1/65 (1.5%)		0/65 (0%)
Thoracic vertebral fracture	1/65 (1.5%)		0/65 (0%)
Musculoskeletal and connective tissue disorders
Spinal osteoarthritis	1/65 (1.5%)		0/65 (0%)
Psychiatric disorders
Major depression	1/65 (1.5%)		0/65 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Rasagiline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/65 (9.2%)		8/65 (12.3%)
Injury, poisoning and procedural complications
Accidental overdose	3/65 (4.6%)		4/65 (6.2%)
Nervous system disorders
Parkinson's disease	4/65 (6.2%)		5/65 (7.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.