Clinical trial NCT00479401: Efficacy, Safety, Tolerability of Pramipexol ER Versus Pramipexol IR Versus Placebo in Early PD Patients
Official title: A Double-blind, Double-dummy, Placebo-controlled, Randomized, Three Parallel Groups Study Comparing the Efficacy, Safety and Tolerability of Pramipexole ER Versus Placebo and Versus Pramipexole IR Administered Orally Over a 26-week Maintenance Phase in Patients With Early Parkinsons Disease (PD).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Early Parkinson Disease (Early PD)
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-05-28
Enrollment: 539
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objectives of this trial conducted in early Parkinson's Disease (PD) patients are to determine the efficacy (as measured by the change from baseline to the end of the maintenance phase in the total score for the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II and III combined), safety, and tolerability of Pramipexole Extended Release (ER) (in daily doses from 0.375mg to 4.5mg q.d.) in comparison to placebo, and to test for non-inferiority between the two formulations (ER and IR) of pramipexole.

In addition, the efficacy of Pramipexole Immediate Release (IR) will be compared to placebo, for assay sensitivity


Eligibility criteria: Inclusion Criteria:

1. Male or female patient with idiopathic Parkinsons disease (PD) confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity.
2. Parkinsons disease diagnosed within 5 years.
3. Patients 30 years of age or older at the time of diagnosis.
4. Modified Hoehn and Yahr stage of 1 to 3.
5. Patients requiring additional therapy/ introduction of therapy (for de novo patients) to treat their parkinsonian symptoms at the time of enrollment (screening visit, V1) according to the investigators judgement.

Exclusion Criteria:

1. Atypical parkinsonian syndromes due to drugs (e.g., metoclopramide, flunarizine), metabolic disorders (e.g., Wilson's disease), encephalitis or degenerative diseases (e.g., progressive supranuclear palsy).
2. Dementia, as defined by a Mini-Mental State Exam score \< 24 at screening visit
3. Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders 4th (DSM-IV)
4. History of psychosis
5. Clinically significant electrocardiogram (ECG) abnormalities at screening visit
6. Clinically significant hypotension
7. Malignant melanoma or history of previously treated malignant melanoma
8. Any other clinically significant disease, whether treated or not, that could put the patient at risk or could prevent compliance or completion of the study
9. Pregnancy
10. Sexually active female of childbearing potential not using a medically approved method of birth control
11. Serum levels of Aspartate Aminotransferase (AST) , Alanine Aminotransferase (ALT), alkaline phosphatases or bilirubin \> 2 Upper Limit of Normal (ULN)
12. Patients with a creatinine clearance \< 50 mL/min
13. Any dopamine agonist (including pramipexole) within 4 weeks prior to baseline visit, or L-Dopa within 8 weeks prior to baseline visit.
14. Total cumulative duration of prior exposure to Levodopa of more than 3 months.
15. Any medication (including intra-muscular formulations) with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit
16. Any of the following drugs within 4 weeks prior to the baseline visit: methylphenidate, cinnarizine, amphetamines.
17. Flunarizine within 3 months prior to baseline visit
18. Known hypersensitivity to Pramipexole or its excipients
19. Drug abuse (including alcohol), according to Investigators judgement, within 2 years prior to screening.
20. Participation in other investigational drug studies or use of other investigational drugs within one month or five times the half-life of the investigational drug

Primary outcomes:
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score
timeFrame: baseline and after 33 weeks treatment
Secondary outcomes:
measure: Percentage of Responders on the Clinical Global Impressions of Improvement (CGI-I) Scale
timeFrame: after 18 weeks of treatment compared to baseline
measure: Percentage of Responders on the Patients Global Impressions of Improvement (PGI-I) Scale
timeFrame: after 18 weeks of treatment compared to baseline
measure: UPDRS II+III Responder Rate (at Least 20% Improvement)
timeFrame: after 33 weeks treatment
measure: UPDRS Part I Change From Baseline
timeFrame: baseline and after 33 weeks treatment
measure: UPDRS Part II Total Score
timeFrame: after 33 weeks treatment
measure: UPDRS Part III Total Score
timeFrame: after 33 weeks treatment
measure: Beck's Depression Inventory Version I A
timeFrame: after 33 weeks treatment
measure: Likert Scale for Pain Related to PD
timeFrame: after 33 weeks treatment
measure: Parkinson's Disease Sleep Scale (PDSS)
timeFrame: after 33 weeks treatment
measure: Change From Baseline in Parkinson's Disease Quality of Life Questionnaire Total Score
timeFrame: after 33 weeks treatment
measure: Change From Baseline in European Quality of Life Visual Analog Scale
timeFrame: after 33 weeks treatment
measure: Patients Who Started to Use L-Dopa Rescue Medication
timeFrame: from trial start on to any time before final assessment of the patient, up to 33 weeks
measure: Number of Patients With Treatment Emergent Abnormal Behaviour as Indicated by the Modified Minnesota Impulsive Disorders Interview (mMIDI Questionnaire)
timeFrame: from trial start on to any time before final assessment of the patient, up to 33 weeks
measure: Possible Clinically Significant Abnormal Laboratory Parameters
timeFrame: baseline and after 33 weeks of treatment
measure: Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events
timeFrame: baseline and after 33 weeks of treatment
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: 248.524.01018 Boehringer Ingelheim Investigational Site
state: Arizona
city: Sun City
country: United States
facility: 248.524.01004 Boehringer Ingelheim Investigational Site
state: Arizona
city: La Jolla
country: United States
facility: 248.524.01016 Boehringer Ingelheim Investigational Site
state: California
city: Oxnard
country: United States
facility: 248.524.01013 Boehringer Ingelheim Investigational Site
state: California
city: Danbury
country: United States
facility: 248.524.01008 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Boca Raton
country: United States
facility: 248.524.01010 Boehringer Ingelheim Investigational Site
state: Florida
city: Augusta
country: United States
facility: 248.524.01014 Boehringer Ingelheim Investigational Site
state: Georgia
city: Chicago
country: United States
facility: 248.524.01012 Boehringer Ingelheim Investigational Site
state: Illinois
city: Kansas City
country: United States
facility: 248.524.01001 Boehringer Ingelheim Investigational Site
state: Kansas
city: Elkridge
country: United States
facility: 248.524.01007 Boehringer Ingelheim Investigational Site
state: Maryland
city: Southfield
country: United States
facility: 248.524.01015 Boehringer Ingelheim Investigational Site
state: Michigan
city: Hattiesburg
country: United States
facility: 248.524.01017 Boehringer Ingelheim Investigational Site
state: Mississippi
city: Commack
country: United States
facility: 248.524.01005 Boehringer Ingelheim Investigational Site
state: New York
city: Dallas
country: United States
facility: 248.524.01002 Boehringer Ingelheim Investigational Site
state: Texas
city: Midvale
country: United States
facility: 248.524.01003 Boehringer Ingelheim Investigational Site
state: Utah
city: Burlington
country: United States
facility: 248.524.01009 Boehringer Ingelheim Investigational Site
state: Vermont
city: Capital Federal
country: Argentina
facility: 248.524.54001 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 248.524.54002 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 248.524.54003 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 248.524.54007 Boehringer Ingelheim Investigational Site
city: Capital Federal
country: Argentina
facility: 248.524.54008 Instituto de Neurociencias de Buenos Aires
city: Capital Federal
country: Argentina
facility: 248.524.54009 Boehringer Ingelheim Investigational Site
city: Mar del Plata
country: Argentina
facility: 248.524.54006 Boehringer Ingelheim Investigational Site
city: Santa Fe
country: Argentina
facility: 248.524.54004 Boehringer Ingelheim Investigational Site
city: Innsbruck
country: Austria
facility: 248.524.43001 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 248.524.43004 Boehringer Ingelheim Investigational Site
city: Olomouc
country: Czech Republic
facility: 248.524.42004 Boehringer Ingelheim Investigational Site
city: Pardubice
country: Czech Republic
facility: 248.524.42003 Boehringer Ingelheim Investigational Site
city: Praha
country: Czech Republic
facility: 248.524.42001 Boehringer Ingelheim Investigational Site
city: Rychnov nad Kneznou
country: Czech Republic
facility: 248.524.42002 Boehringer Ingelheim Investigational Site
city: Hyvinkää
country: Finland
facility: 248.524.35803 Boehringer Ingelheim Investigational Site
city: Oulu
country: Finland
facility: 248.524.35801 Boehringer Ingelheim Investigational Site
city: Tampere
country: Finland
facility: 248.524.35802 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 248.524.49002 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 248.524.49003 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 248.524.49011 Boehringer Ingelheim Investigational Site
city: Bremerhaven
country: Germany
facility: 248.524.49008 Boehringer Ingelheim Investigational Site
city: Dresden
country: Germany
facility: 248.524.49006 Boehringer Ingelheim Investigational Site
city: Göttingen
country: Germany
facility: 248.524.49007 Boehringer Ingelheim Investigational Site
city: Kassel
country: Germany
facility: 248.524.49001 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 248.524.49004 Boehringer Ingelheim Investigational Site
city: Marburg
country: Germany
facility: 248.524.49005 Boehringer Ingelheim Investigational Site
city: Eger
country: Hungary
facility: 248.524.36007 Boehringer Ingelheim Investigational Site
city: Györ
country: Hungary
facility: 248.524.36005 Boehringer Ingelheim Investigational Site
city: Miskolc
country: Hungary
facility: 248.524.36008 Boehringer Ingelheim Investigational Site
city: Sopron
country: Hungary
facility: 248.524.36004 Boehringer Ingelheim Investigational Site
city: Szeged
country: Hungary
facility: 248.524.36001 Boehringer Ingelheim Investigational Site
city: Szeged
country: Hungary
facility: 248.524.36006 Boehringer Ingelheim Investigational Site
city: Szombathely
country: Hungary
facility: 248.524.36003 Boehringer Ingelheim Investigational Site
city: Zalaegerszeg
country: Hungary
facility: 248.524.36002 Boehringer Ingelheim Investigational Site
city: Chennai
country: India
facility: 248.524.91002 Boehringer Ingelheim Investigational Site
city: Hyderabad
country: India
facility: 248.524.91009 Boehringer Ingelheim Investigational Site
city: Hyderabad
country: India
facility: 248.524.91010 Boehringer Ingelheim Investigational Site
city: Karnataka
country: India
facility: 248.524.91001 Boehringer Ingelheim Investigational Site
city: Maharashtra
country: India
facility: 248.524.91005 Boehringer Ingelheim Investigational Site
city: Maharashtra
country: India
facility: 248.524.91007 Boehringer Ingelheim Investigational Site
city: New Delhi
country: India
facility: 248.524.91004 Boehringer Ingelheim Investigational Site
city: New Delhi
country: India
facility: 248.524.91006 Boehringer Ingelheim Investigational Site
city: Pune
country: India
facility: 248.524.91011 Boehringer Ingelheim Investigational Site
city: Aomori, Aomori
country: Japan
facility: 248.524.81010 Boehringer Ingelheim Investigational Site
city: Bunkyo-ku, Tokyo
country: Japan
facility: 248.524.81001 Boehringer Ingelheim Investigational Site
city: Fuchu, Tokyo
country: Japan
facility: 248.524.81005 Boehringer Ingelheim Investigational Site
city: Fujisawa, Kanagawa
country: Japan
facility: 248.524.81011 Boehringer Ingelheim Investigational Site
city: Fukuoka, Fukuoka
country: Japan
facility: 248.524.81013 Boehringer Ingelheim Investigational Site
city: Iwamizawa,Hokkaido
country: Japan
facility: 248.524.81015 Boehringer Ingelheim Investigational Site
city: Kodaira, Tokyo
country: Japan
facility: 248.524.81003 Boehringer Ingelheim Investigational Site
city: Kyoto, Kyoto
country: Japan
facility: 248.524.81014 Boehringer Ingelheim Investigational Site
city: Morioka, Iwate
country: Japan
facility: 248.524.81009 Boehringer Ingelheim Investigational Site
city: Okayama, Okayama
country: Japan
facility: 248.524.81008 Boehringer Ingelheim Investigational Site
city: Ota-ku, Tokyo
country: Japan
facility: 248.524.81006 Boehringer Ingelheim Investigational Site
city: Sagamihara, Kanagawa
country: Japan
facility: 248.524.81004 Boehringer Ingelheim Investigational Site
city: Shimogyo-ku, Kyoto, Kyoto
country: Japan
facility: 248.524.81007 Boehringer Ingelheim Investigational Site
city: Shiroishi, Miyagi
country: Japan
facility: 248.524.81012 Boehringer Ingelheim Investigational Site
city: Takamatsu, Kagawa
country: Japan
facility: 248.524.81002 Boehringer Ingelheim Investigational Site
city: Kuala Lumpur
country: Malaysia
facility: 248.524.60001 Boehringer Ingelheim Investigational Site
city: Kuala Terengganu
country: Malaysia
facility: 248.524.60004 Boehringer Ingelheim Investigational Site
city: Pulau Pinang
country: Malaysia
facility: 248.524.60002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 248.524.07001 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 248.524.07002 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 248.524.07003 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 248.524.07004 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 248.524.07005 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 248.524.07006 Boehringer Ingelheim Investigational Site
city: Dubnica nad Vahom
country: Slovakia
facility: 248.524.42103 Boehringer Ingelheim Investigational Site
city: Trnava
country: Slovakia
facility: 248.524.42101 Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: 248.524.88603 Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: 248.524.88605 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 248.524.88601 Boehringer Ingelheim Investigational Site
city: Taoyuan
country: Taiwan
facility: 248.524.88602 Boehringer Ingelheim Investigational Site
city: Kiev
country: Ukraine
facility: 248.524.38005 Boehringer Ingelheim Investigational Site
city: Lvov
country: Ukraine
facility: 248.524.38001 Boehringer Ingelheim Investigational Site
city: Uzhgorod
country: Ukraine
facility: 248.524.38002 Boehringer Ingelheim Investigational Site
city: Vinnytzya
country: Ukraine
facility: 248.524.38003 Boehringer Ingelheim Investigational Site
city: Zaporizhzhya
country: Ukraine
facility: 248.524.38004 Boehringer Ingelheim Investigational Site
city: Zaporozhye
country: Ukraine
facility: 248.524.38006 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: