Rasagiline as Add on to Dopamine Agonists in the Treatmen... | NCT01049984

NCT01049984

Status Module

Sponsor/Collaborators Module

Name	Class
H. Lundbeck A/S	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Rasagiline 1 mg	Experimental	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Drug: Rasagiline
Placebo	Placebo Comparator	Participants took a matching placebo tablet once daily for 18 weeks.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Rasagiline	Drug	1mg tablet daily for 18 weeks	Rasagiline 1 mg	TVP-1012

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III	The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, three of which are totaled and reported in this outcome. Part I is a clinician's evaluation of mentation (mental activity or state of mind), cognition (ability to acquire knowledge), behaviour and mood. Part II is the participants' evaluation of the disease's impact on normal activities. Part III is a clinician's evaluation of motor function. Parts I, II, and III contain a total of 31 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-124. Negative change from baseline values indicate improvement. All site raters (medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits.	Day 0 (baseline), Week 18

Secondary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living	The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. UPDRS contains four parts, the second of which is reported in this outcome. Part II is the participants' evaluation of the disease's impact on normal activities. Part II contains a total of 13 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-52. Negative change from baseline values indicate improvement.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

receiving stable dose of oral ropinirole or pramipexole whose symptoms are not optimally controlled or whose oral dopamine agonist titration regimen was truncated due to intolerability:
1) Minimum dose of agonist will be 6 mg/day for ropinirole and 1.0 mg/day for pramipexole
2) Stable dopamine agonist treatment must have been ongoing for ≥ 30 days, no longer than 5 years preceding baseline
Males and females. Women of childbearing potential must agree to practice an acceptable method of birth control.
Idiopathic Parkinson Disease confirmed at baseline by presence of at least 2 cardinal signs (resting tremor, bradykinesia, rigidity), w/o other known or suspected cause of Parkinsonism
Hoehn & Yahr > 1 (symptoms on only one side of the body) with treatment and < 3 (mild to moderate bilateral disease; some postural instability; physically independent).
Dopamine agonist dose must be stable for ≥30 days preceding the baseline visit.
For patients who are receiving amantadine or anticholinergics, the dose must have been stable for ≥30 days prior to screening.
Medically stable outpatients (Investigator's judgment).

Exclusion Criteria:

receive rasagiline or other monoamine oxidase (MAO) inhibitors 60 days preceding baseline
receive levodopa > 21 consecutive days within 90 days prior baseline
moderate to severe motor fluctuations
hepatic impairment
investigational medications 30 days preceding baseline
dopamine agonist use > 5 years prior to baseline
major depression as defined by Beck Depression Inventory (BDI) short form score greater than 14
significant cognitive impairment as defined by Mini-Mental State Exam (MMSE) score less than 26.
impulse control disorder (ICD) based on the Questionnaire for Impulsive-compulsive Disorders in Parkinson's Disease form (QUIP).
pregnant or lactating or planning on becoming pregnant in the next 18 weeks
uncontrolled hypertension. Patients whose hypertension is controlled with medications are eligible.
Concomitant monoamine oxidase (MAO) inhibitors or medicines contraindicated w/ MAO inhibitors not allowed

Contacts/Locations Module

Name	Affiliation	Role
Azhar Choudhry, M.D.	Teva Neuroscience, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Teva Investigational Site 34		Phoenix	Arizona		United States
Teva Investigational Site 42

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Rasagiline 1 mg	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
FG001	Placebo	Participants took a matching placebo tablet once daily for 18 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Arm/Group Information

ID	Title	Description
BG000	Rasagiline 1 mg	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
BG001	Placebo	Participants took a matching placebo tablet once daily for 18 weeks.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00062.3± 9.27 BG00162.8± 10.06 BG00262.5± 9.67

Age, Customized

Number

participants

Title

Denominators

Categories

30 to <65 years

Title	Measurements
	BG00097 BG00189 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00053 BG00153 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0007 BG0019 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Parkinson's Disease Duration

Years since first diagnosis. Data based on the modified intent to treat population of 159, 162 participants.

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG0002.19± 2.224 BG0012.07± 1.940

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III

The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, three of which are totaled and reported in this outcome. Part I is a clinician's evaluation of mentation (mental activity or state of mind), cognition (ability to acquire knowledge), behaviour and mood. Part II is the participants' evaluation of the disease's impact on normal activities. Part III is a clinician's evaluation of motor function. Parts I, II, and III contain a total of 31 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-124. Negative change from baseline values indicate improvement.

All site raters (medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant) received training on how to complete the UPDRS. The same site rater completed the UPDRS at all visits.

Modified intent to treat population - all randomized participants who took at least 1 dose of study drug and had both a baseline and at least 1 post-baseline efficacy assessment. Several participants had missing UPDRS items at baseline and during treatment; therefore the total UPDRS for these participants was set as missing.

Posted

Least Squares Mean

Standard Error

units on a scale

Day 0 (baseline), Week 18

ID	Title	Description
OG000	Rasagiline 1 mg	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
OG001	Placebo	Participants took a matching placebo tablet once daily for 18 weeks.

Units	Counts
Participants	OG000158 OG001157

Title

Denominators

Categories

Title	Measurements
	OG000-3.6± 0.68 OG001-1.2± 0.68

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA	Repeated measures model with baseline score as a covariate and factors Treatment, Week in Study, Pooled Center and Week by Treatment interaction.	0.012	All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted.	Mean Difference (Final Values)	-2.4			2-Sided	95	-4.3	-0.5				No	Superiority or Other

Secondary

Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living

The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. UPDRS contains four parts, the second of which is reported in this outcome. Part II is the participants' evaluation of the disease's impact on normal activities. Part II contains a total of 13 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-52. Negative change from baseline values indicate improvement.

Modified intent to treat population - all randomized participants who took at least 1 dose of study drug and had both a baseline and at least 1 post-baseline efficacy assessment. Several participants had missing UPDRS items at baseline and during treatment for subscale II, and therefore that subscale was set as missing.

Posted

Least Squares Mean

Standard Error

units on a scale

Day 0 (baseline), Week 18

ID	Title	Description
OG000	Rasagiline 1 mg	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
OG001	Placebo	Participants took a matching placebo tablet once daily for 18 weeks.

Secondary

Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function

The UPDRS was developed as a comprehensive tool to monitor the impact of Parkinson's Disease and the degree of disability caused. Version 3 of UPDRS contains four parts, the third of which is reported in this outcome. Part III is a clinician's evaluation of motor function. Part III contains 14 questions, which are each rated on a scale of 0 (normal or no disease effect) to 4 (maximum negative effect), for a total scale of 0-56. Negative change from baseline values indicate improvement.

Modified intent to treat population - all randomized participants who took at least 1 dose of study drug and had both a baseline and at least 1 post-baseline efficacy assessment. Several participants had missing UPDRS items at baseline and during treatment for subscale III, and therefore that subscale was set as missing.

Posted

Least Squares Mean

Standard Error

units on a scale

Day 0 (baseline), Week 18

ID	Title	Description
OG000	Rasagiline 1 mg	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
OG001	Placebo	Participants took a matching placebo tablet once daily for 18 weeks.

Secondary

Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater

CGI is used by the site rater to rate participants total improvement during the study whether or not, in the investigators' judgment, it is due entirely to drug treatment. Specifically, site raters are asked to compare the participants condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse).

Site raters can be the medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant.

Modified intent to treat

Posted

Number

participants

18 weeks

ID	Title	Description
OG000	Rasagiline 1 mg	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
OG001	Placebo	Participants took a matching placebo tablet once daily for 18 weeks.

Units	Counts
Participants

Secondary

Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant

CGI is used by the participant to rate his/her total improvement during the study. Specifically, participants are asked to compare their condition at the beginning of the study to his/her condition at Week 18, how much has he/she changed? Answers are 0 (not assessed), 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse), 7(very much worse).

Modified intent to treat

Posted

Number

participants

18 weeks

ID	Title	Description
OG000	Rasagiline 1 mg	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
OG001	Placebo	Participants took a matching placebo tablet once daily for 18 weeks.

Units	Counts
Participants	OG000

Secondary

Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater

Site raters were asked: Considering your total clinical experience with the particular population, how ill is the patient at this time? Answers were based on a 0-7 scale, with 0=not assessed, 1= normal, not at all ill, and 7= among the most extremely ill of patients.

Site raters can be the medical doctor [MD], doctor of osteopathy [DO], nurse practitioner, or physician assistant.

Modified intent to treat

Posted

Number

participants

Day 0 (baseline), Week 18

ID	Title	Description
OG000	Rasagiline 1 mg	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
OG001	Placebo	Participants took a matching placebo tablet once daily for 18 weeks.

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Placebo	Participants took a matching placebo tablet once daily for 18 weeks.			5	164	44	164
EG001	Rasagiline 1 mg	Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.			8	162	55	162

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
MYOCARDIAL ISCHAEMIA	Cardiac disorders	MedDRA (12.0)	Non-systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected162 at risk
CHOLECYSTITIS ACUTE	Hepatobiliary disorders	MedDRA (12.0)	Non-systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected162 at risk
CHOLELITHIASIS	Hepatobiliary disorders	MedDRA (12.0)	Non-systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected162 at risk
ANKLE FRACTURE	Injury, poisoning and procedural complications	MedDRA (12.0)	Non-systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected162 at risk
FRACTURED SACRUM	Injury, poisoning and procedural complications	MedDRA (12.0)	Non-systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected162 at risk
HUMERUS FRACTURE	Injury, poisoning and procedural complications	MedDRA (12.0)	Non-systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected162 at risk
INTERVERTEBRAL DISC DISORDER	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Non-systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected162 at risk
LUMBAR SPINAL STENOSIS	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Non-systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected162 at risk
SPONDYLOLISTHESIS	Musculoskeletal and connective tissue disorders	MedDRA (12.0)	Non-systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected162 at risk
PARKINSON'S DISEASE	Nervous system disorders	MedDRA (12.0)	Non-systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected162 at risk
PRESYNCOPE	Nervous system disorders	MedDRA (12.0)	Non-systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected162 at risk
SYNCOPE	Nervous system disorders	MedDRA (12.0)	Non-systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected162 at risk
HAEMATURIA	Renal and urinary disorders	MedDRA (12.0)	Non-systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected162 at risk
URINARY RETENTION	Renal and urinary disorders	MedDRA (12.0)	Non-systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected162 at risk
DYSPNOEA	Respiratory, thoracic and mediastinal disorders	MedDRA (12.0)	Non-systematic Assessment	EG0001 events1 affected164 at risk EG0010 events0 affected162 at risk
INTERVERTEBRAL DISC OPERATION	Surgical and medical procedures	MedDRA (12.0)	Non-systematic Assessment	EG0000 events0 affected164 at risk EG0011 events1 affected162 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
NAUSEA	Gastrointestinal disorders	MedDRA (12.0)	Non-systematic Assessment	EG0007 events7 affected164 at risk EG00110 events10 affected162 at risk
OEDEMA PERIPHERAL	General disorders	MedDRA (12.0)	Non-systematic Assessment	EG0008 events7 affected164 at risk EG00112 events12 affected162 at risk
FALL	Injury, poisoning and procedural complications	MedDRA (12.0)	Non-systematic Assessment	EG0002 events2 affected164 at risk EG0019 events9 affected162 at risk
DIZZINESS	Nervous system disorders	MedDRA (12.0)	Non-systematic Assessment	EG00011 events10 affected164 at risk EG00114 events12 affected162 at risk
HEADACHE	Nervous system disorders	MedDRA (12.0)	Non-systematic Assessment	EG0008 events7 affected164 at risk EG00115 events10 affected162 at risk
SOMNOLENCE	Nervous system disorders	MedDRA (12.0)	Non-systematic Assessment	EG00011 events11 affected164 at risk EG00111 events11 affected162 at risk
TREMOR	Nervous system disorders	MedDRA (12.0)	Non-systematic Assessment	EG00010 events10 affected164 at risk EG0018 events7 affected162 at risk

ID	Term
D010300	Parkinson Disease

Ancestor Terms

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009069	Movement Disorders
D000080874	Synucleinopathies
D019636	Neurodegenerative Diseases

ID	Term
C031967	rasagiline