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

A Double-blind, Placebo Controlled, Randomized, Multicenter Study to Assess the Safety and Clinical Benefit of Rasagiline as an Add on Therapy to Stable Dose of Dopamine Agonists in the Treatment of Early Parkinson's Disease

To assess the efficacy of rasagiline 1 mg as a first add-on treatment to dopamine agonist therapy in early Parkinson Disease (PD) patients, , not optimally controlled on dopamine agonists as compared to placebo.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Rasagiline; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 328
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Teva Investigational Site 34
    • Sun City, Arizona, United States
      • Teva Investigational Site 42
  • California
    • Fountain Valley, California, United States
      • Teva Investigational Site 15
    • Fresno, California, United States
      • Teva Investigational Site 19
    • Fresno, California, United States
      • Teva Investigational Site 36
    • La Jolla, California, United States
      • Teva Investigational Site 04
    • Reseda, California, United States
      • Teva Investigational Site 29
    • San Francisco, California, United States
      • Teva Investigational Site 69
    • Sunnyvale, California, United States
      • Teva Investigational Site 02
    • Ventura, California, United States
      • Teva Investigational Site 43
  • Connecticut
    • Fairfield, Connecticut, United States
      • Teva Investigational Site 44
    • Manchester, Connecticut, United States
      • Teva Investigational Site 07
  • Delaware
    • Newark, Delaware, United States
      • Teva Investigational Site 25
  • Florida
    • Atlantis, Florida, United States
      • Teva Investigative Site 63
    • Boca Raton, Florida, United States
      • Teva Investigational Site 30
    • Clearwater, Florida, United States
      • Teva Investigational Site 13
    • Sunrise, Florida, United States
      • Teva Investigational Site 70
    • Tampa, Florida, United States
      • Teva Investigational Site 41
    • Vero Beach, Florida, United States
      • Teva Investigational Site 61
  • Georgia
    • Decatur, Georgia, United States
      • Teva Investigational Site 01
  • Idaho
    • Boise, Idaho, United States
      • Teva Investigational Site 58
  • Illinois
    • Glenview, Illinois, United States
      • Teva Investigational Site 49
    • Peoria, Illinois, United States
      • Teva Investigational Site 23
  • Indiana
    • Indianapolis, Indiana, United States
      • Teva Investigational Site 47
    • Indianapolis, Indiana, United States
      • Teva Investigational Site 67
    • Indianapolis, Indiana, United States
      • Teva Investigational Site 76
  • Iowa
    • Des Moines, Iowa, United States
      • Teva Investigational Site 55
  • Kentucky
    • Lexington, Kentucky, United States
      • Teva Investigational Site 17
    • Paducah, Kentucky, United States
      • Teva Investigational Site 27
  • Maine
    • Scarborough, Maine, United States
      • Teva Investigational Site 56
  • Maryland
    • Elkridge, Maryland, United States
      • Teva Investigational Site 62
  • Massachusetts
    • Springfield, Massachusetts, United States
      • Teva Investigational Site 51
  • Michigan
    • Detroit, Michigan, United States
      • Teva Investigational Site 11
    • West Bloomfield, Michigan, United States
      • Teva Investigational Site 33
  • Minnesota
    • Golden Valley, Minnesota, United States
      • Teva Investigational Site 39
  • Missouri
    • St. Louis, Missouri, United States
      • Teva Investigational Site 22
  • Montana
    • Great Falls, Montana, United States
      • Teva Investigational Site 08
    • Missoula, Montana, United States
      • Teva Investigational Site 59
  • Nevada
    • Las Vegas, Nevada, United States
      • Teva Investigational Site 60
  • New Jersey
    • Somerset, New Jersey, United States
      • Teva Investigational Site 14
  • New York
    • Commack, New York, United States
      • Teva Investigational Site 03
    • Plainview, New York, United States
      • Teva Investigational Site 38
  • North Carolina
    • Asheville, North Carolina, United States
      • Teva Investigational Site 05
    • Charlotte, North Carolina, United States
      • Teva Investigational Site 31
    • Raleigh, North Carolina, United States
      • Teva Investigational Site 28
  • North Dakota
    • Fargo, North Dakota, United States
      • Teva Investigational Site 26
  • Ohio
    • Cincinnati, Ohio, United States
      • Teva Investigational Site 35
    • Cincinnati, Ohio, United States
      • Teva Investigational Site 68
  • Oklahoma
    • Tulsa, Oklahoma, United States
      • Teva Investigational Site 64
  • Oregon
    • Medford, Oregon, United States
      • Teva Investigational Site 21
    • Portland, Oregon, United States
      • Teva Investigational Site 40
  • Tennessee
    • Cordova, Tennessee, United States
      • Teva Investigative Site 65
  • Texas
    • Brownwood, Texas, United States
      • Teva Investigational Site 71
    • San Antonio, Texas, United States
      • Teva Investigational Site 18
    • Temple, Texas, United States
      • Teva Investigational Site 32
  • Virginia
    • Richmond, Virginia, United States
      • Teva Investigational Site 09
    • Virginia Beach, Virginia, United States
      • Teva Investigational Site 46
  • Wisconsin
    • Madison, Wisconsin, United States
      • Teva Investigational Site 77

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Rasagiline 1 mg; Participants took a 1 mg rasagiline tablet orally each day for 18 weeks.	Drug: Rasagiline; 1mg tablet daily for 18 weeks; Other Names: TVP-1012; AZILECT®
PLACEBO_COMPARATOR: Placebo; Participants took a matching placebo tablet once daily for 18 weeks.	Drug: Placebo; one tablet daily for 18 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 Outcome Measures

Outcome Measure	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.	Day 0 (baseline), Week 18
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. 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
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.	18 weeks
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).	18 weeks
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.	Day 0 (baseline), Week 18

Collaborators and Investigators

• Sponsor: Teva Neuroscience, Inc.
• Collaborators: H. Lundbeck A/S
• Investigators: Study Director: Azhar Choudhry, M.D., Teva Neuroscience, Inc.

Study record dates

Study Major Dates

• Study Start: December 1, 2009
• Primary Completion (ACTUAL): October 1, 2012
• Study Completion (ACTUAL): October 1, 2012

Study Registration Dates

• First Submitted: January 13, 2010
• First Submitted That Met QC Criteria: January 14, 2010
• First Posted (ESTIMATE): January 15, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): May 20, 2016
• Last Update Submitted That Met QC Criteria: April 20, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Levodopa; UPDRS; rasagiline; Clinical Global Evaluation Illness Severity score; Clinical Global Evaluation Improvement; B-SIT; SCOPA - Sleep Daytime Sleepiness; PDQ -39; SCOPA - Cognition; Dopamine Agonist Therapy; monoamine oxidase type B inhibitor
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Monoamine Oxidase Inhibitors; Rasagiline
• Other Study ID Numbers: TVP-1012/PM103