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Rasagiline as Add on to Dopamine Agonists in the Treatment of Parkinson's Disease (ANDANTE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01049984
Recruitment Status : Completed
First Posted : January 15, 2010
Results First Posted : October 15, 2014
Last Update Posted : May 20, 2016
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Neuroscience, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Parkinson's Disease
Interventions Drug: Rasagiline
Drug: Placebo
Enrollment 328
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Rasagiline 1 mg Placebo
Hide Arm/Group Description Participants took a 1 mg rasagiline tablet orally each day for 18 weeks. Participants took a matching placebo tablet once daily for 18 weeks.
Period Title: Overall Study
Started 163 165
Safety Population 162 [1] 164 [1]
Modified Intent-to-treat Pop 159 [2] 162 [2]
Completed 144 146
Not Completed 19 19
Reason Not Completed
Withdrawal by Subject             1             5
Protocol Violation             3             4
Lost to Follow-up             2             1
Adverse Event             13             7
Treatment failure             0             2
[1]
One patient was randomized but not dosed; omitted from safety population
[2]
Took >= 1 dose of study drug and had both baseline and at least 1 post-baseline efficacy assessment
Arm/Group Title Rasagiline 1 mg Placebo Total
Hide Arm/Group Description Participants took a 1 mg rasagiline tablet orally each day for 18 weeks. Participants took a matching placebo tablet once daily for 18 weeks. Total of all reporting groups
Overall Number of Baseline Participants 162 164 326
Hide Baseline Analysis Population Description
Safety population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 162 participants 164 participants 326 participants
62.3  (9.27) 62.8  (10.06) 62.5  (9.67)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 162 participants 164 participants 326 participants
30 to <65 years 97 89 186
65 to <75 years 49 60 109
>=75 years 16 15 31
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 162 participants 164 participants 326 participants
Female
53
  32.7%
53
  32.3%
106
  32.5%
Male
109
  67.3%
111
  67.7%
220
  67.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 162 participants 164 participants 326 participants
Hispanic or Latino
7
   4.3%
9
   5.5%
16
   4.9%
Not Hispanic or Latino
154
  95.1%
155
  94.5%
309
  94.8%
Unknown or Not Reported
1
   0.6%
0
   0.0%
1
   0.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 162 participants 164 participants 326 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   1.2%
3
   1.8%
5
   1.5%
Native Hawaiian or Other Pacific Islander
0
   0.0%
2
   1.2%
2
   0.6%
Black or African American
3
   1.9%
7
   4.3%
10
   3.1%
White
156
  96.3%
151
  92.1%
307
  94.2%
More than one race
1
   0.6%
1
   0.6%
2
   0.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Parkinson's Disease Duration   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 162 participants 164 participants 326 participants
2.19  (2.224) 2.07  (1.940) 2.13  (2.083)
[1]
Measure Description: Years since first diagnosis. Data based on the modified intent to treat population of 159, 162 participants.
1.Primary Outcome
Title Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III
Hide Description

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.

Time Frame Day 0 (baseline), Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Rasagiline 1 mg Placebo
Hide Arm/Group Description:
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
Participants took a matching placebo tablet once daily for 18 weeks.
Overall Number of Participants Analyzed 158 157
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.6  (0.68) -1.2  (0.68)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rasagiline 1 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted.
Method ANCOVA
Comments Repeated measures model with baseline score as a covariate and factors Treatment, Week in Study, Pooled Center and Week by Treatment interaction.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.4
Confidence Interval (2-Sided) 95%
-4.3 to -0.5
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living
Hide Description 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.
Time Frame Day 0 (baseline), Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Rasagiline 1 mg Placebo
Hide Arm/Group Description:
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
Participants took a matching placebo tablet once daily for 18 weeks.
Overall Number of Participants Analyzed 158 160
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-0.1  (0.27) 0.3  (0.27)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rasagiline 1 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.301
Comments All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted.
Method ANCOVA
Comments Repeated measures model with baseline score as a covariate and factors Treatment, Week in Study, Pooled Center and Week by Treatment interaction.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.1 to 0.3
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function
Hide Description

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.

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

Time Frame Day 0 (baseline), Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Rasagiline 1 mg Placebo
Hide Arm/Group Description:
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
Participants took a matching placebo tablet once daily for 18 weeks.
Overall Number of Participants Analyzed 159 158
Least Squares Mean (Standard Error)
Unit of Measure: units on a scale
-3.4  (0.48) -1.6  (0.48)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rasagiline 1 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted.
Method ANCOVA
Comments Repeated measures model with baseline score as a covariate and factors Treatment, Week in Study, Pooled Center and Week by Treatment interaction.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-3.1 to -0.5
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater
Hide Description

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.

Time Frame 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent to treat
Arm/Group Title Rasagiline 1 mg Placebo
Hide Arm/Group Description:
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
Participants took a matching placebo tablet once daily for 18 weeks.
Overall Number of Participants Analyzed 159 162
Measure Type: Number
Unit of Measure: participants
Not assessed (0) 0 1
Very much improved (1) 5 5
Much improved (2) 21 20
Minimally improved (3) 45 39
No change (4) 63 53
Minimally worse (5) 21 42
Much worse (6) 3 1
Very much worse (7) 1 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rasagiline 1 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.255
Comments All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted. Only participants with assessment (>0) are included in the CMH test.
Method Cochran-Mantel-Haenszel
Comments CMH used the proportion of participants in each category between the two treatment arms, with treatment and pooled center as strata.
5.Secondary Outcome
Title Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant
Hide Description 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).
Time Frame 18 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent to treat
Arm/Group Title Rasagiline 1 mg Placebo
Hide Arm/Group Description:
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
Participants took a matching placebo tablet once daily for 18 weeks.
Overall Number of Participants Analyzed 159 162
Measure Type: Number
Unit of Measure: participants
Not assessed (0) 0 1
Very much improved (1) 7 7
Much improved (2) 18 18
Minimally improved (3) 39 40
No change (4) 52 52
Minimally worse (5) 36 35
Much worse (6) 5 8
Very much worse (7) 2 1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rasagiline 1 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.996
Comments All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted. Only participants with assessment (>0) are included in the CMH test.
Method Cochran-Mantel-Haenszel
Comments CMH used the proportion of participants in each category between the two treatment arms, with treatment and pooled center as strata.
6.Secondary Outcome
Title Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater
Hide Description

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.

Time Frame Day 0 (baseline), Week 18
Hide Outcome Measure Data
Hide Analysis Population Description
Modified intent to treat
Arm/Group Title Rasagiline 1 mg Placebo
Hide Arm/Group Description:
Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
Participants took a matching placebo tablet once daily for 18 weeks.
Overall Number of Participants Analyzed 159 162
Measure Type: Number
Unit of Measure: participants
Day 0: Not assessed (0) 0 0
Day 0: Normal, not at all ill (1) 4 5
Day 0: Borderline ill (2) 18 26
Day 0: Mildly Ill (3) 95 100
Day 0: Moderately Ill (4) 39 28
Day 0: Markedly ill (5) 1 2
Day 0: Severely ill (6) 0 0
Day 0: Among the most extremely ill (7) 0 0
Week 18: Not assessed (0) 0 2
Week 18: Normal, not at all ill (1) 10 5
Week 18: Borderline ill (2) 28 33
Week 18: Mildly ill (3) 90 89
Week 18: Moderately ill (4) 29 31
Week 18: Markedly ill (5) 2 1
Week 18: Severely ill (6) 0 1
Week 18: Among the most extremely ill (7) 0 0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Rasagiline 1 mg, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.967
Comments All analyses were performed at the 2-sided 0.05 significance level. P values were not adjusted. Only participants with assessment (>0) are included in the CMH test.
Method Cochran-Mantel-Haenszel
Comments CMH used the proportion of participants in each category between the two treatment arms, with treatment, pooled center, and baseline value as strata.
Time Frame Day 0 (post treatment) to Week 18
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Placebo Rasagiline 1 mg
Hide Arm/Group Description Participants took a matching placebo tablet once daily for 18 weeks. Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.
All-Cause Mortality
Placebo Rasagiline 1 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Placebo Rasagiline 1 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/164 (3.05%)      8/162 (4.94%)    
Cardiac disorders     
MYOCARDIAL ISCHAEMIA * 1  1/164 (0.61%)  1 0/162 (0.00%)  0
Hepatobiliary disorders     
CHOLECYSTITIS ACUTE * 1  0/164 (0.00%)  0 1/162 (0.62%)  1
CHOLELITHIASIS * 1  1/164 (0.61%)  1 0/162 (0.00%)  0
Injury, poisoning and procedural complications     
ANKLE FRACTURE * 1  0/164 (0.00%)  0 1/162 (0.62%)  1
FRACTURED SACRUM * 1  1/164 (0.61%)  1 0/162 (0.00%)  0
HUMERUS FRACTURE * 1  0/164 (0.00%)  0 1/162 (0.62%)  1
Musculoskeletal and connective tissue disorders     
INTERVERTEBRAL DISC DISORDER * 1  0/164 (0.00%)  0 1/162 (0.62%)  1
LUMBAR SPINAL STENOSIS * 1  0/164 (0.00%)  0 1/162 (0.62%)  1
SPONDYLOLISTHESIS * 1  0/164 (0.00%)  0 1/162 (0.62%)  1
Nervous system disorders     
PARKINSON'S DISEASE * 1  1/164 (0.61%)  1 0/162 (0.00%)  0
PRESYNCOPE * 1  0/164 (0.00%)  0 1/162 (0.62%)  1
SYNCOPE * 1  0/164 (0.00%)  0 1/162 (0.62%)  1
Renal and urinary disorders     
HAEMATURIA * 1  1/164 (0.61%)  1 0/162 (0.00%)  0
URINARY RETENTION * 1  1/164 (0.61%)  1 0/162 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
DYSPNOEA * 1  1/164 (0.61%)  1 0/162 (0.00%)  0
Surgical and medical procedures     
INTERVERTEBRAL DISC OPERATION * 1  0/164 (0.00%)  0 1/162 (0.62%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Rasagiline 1 mg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   44/164 (26.83%)      55/162 (33.95%)    
Gastrointestinal disorders     
NAUSEA * 1  7/164 (4.27%)  7 10/162 (6.17%)  10
General disorders     
OEDEMA PERIPHERAL * 1  7/164 (4.27%)  8 12/162 (7.41%)  12
Injury, poisoning and procedural complications     
FALL * 1  2/164 (1.22%)  2 9/162 (5.56%)  9
Nervous system disorders     
DIZZINESS * 1  10/164 (6.10%)  11 12/162 (7.41%)  14
HEADACHE * 1  7/164 (4.27%)  8 10/162 (6.17%)  15
SOMNOLENCE * 1  11/164 (6.71%)  11 11/162 (6.79%)  11
TREMOR * 1  10/164 (6.10%)  10 7/162 (4.32%)  8
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (12.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. Sponsor may remove information that is considered confidential and/or proprietary other than Study data and results.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Director, Clinical Research
Organization: Teva Branded Pharmaceutical Products, R&D Inc.
Phone: 215-591-3000
EMail: ustevatrials@tevapharm.com
Layout table for additonal information
Responsible Party: Teva Pharmaceutical Industries ( Teva Neuroscience, Inc. )
ClinicalTrials.gov Identifier: NCT01049984    
Other Study ID Numbers: TVP-1012/PM103
First Submitted: January 13, 2010
First Posted: January 15, 2010
Results First Submitted: October 9, 2014
Results First Posted: October 15, 2014
Last Update Posted: May 20, 2016