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

This study has been completed.
Sponsor:
Collaborator:
H. Lundbeck A/S
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Neuroscience, Inc. )
ClinicalTrials.gov Identifier:
NCT01049984
First received: January 13, 2010
Last updated: October 9, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Parkinson's Disease
Drug: Rasagiline
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Parts I, II and III [ Time Frame: Day 0 (baseline), Week 18 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part II - Activities of Daily Living [ Time Frame: Day 0 (baseline), Week 18 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline to Week 18 in the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score for Part III - Motor Function [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

    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


  • Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Site Rater [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

    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.


  • Clinical Global Improvement (CGI) Score at Week 18 As Assessed by the Participant [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]
    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).

  • Illness Severity Score at Day 0 and Week 18 As Assessed by the Site Rater [ Time Frame: 18 weeks ] [ Designated as safety issue: No ]

    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.



Enrollment: 328
Study Start Date: December 2009
Study Completion Date: October 2012
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   30 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01049984

  Show 58 Study Locations
Sponsors and Collaborators
Teva Neuroscience, Inc.
H. Lundbeck A/S
Investigators
Study Director: Azhar Choudhry, M.D. Teva Neuroscience, Inc.
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( Teva Neuroscience, Inc. )
ClinicalTrials.gov Identifier: NCT01049984     History of Changes
Other Study ID Numbers: TVP-1012/PM103
Study First Received: January 13, 2010
Results First Received: October 9, 2014
Last Updated: October 9, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Teva Pharmaceutical Industries:
Parkinson's Disease
UPDRS
Clinical Global Evaluation Illness Severity score
Clinical Global Evaluation Improvement
B-SIT
SCOPA - Sleep Daytime Sleepiness
PDQ -39
SCOPA - Cognition
Levodopa
rasagiline
Dopamine Agonist Therapy
monoamine oxidase type B inhibitor

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders
Dopamine
Dopamine Agents
Dopamine Agonists
Rasagiline
Autonomic Agents
Cardiotonic Agents
Cardiovascular Agents
Central Nervous System Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Monoamine Oxidase Inhibitors
Neuroprotective Agents
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sympathomimetics
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014