Efficacy, Safety, Tolerability of Pramipexol ER Versus Pramipexol IR Versus Placebo in Early PD Patients

Phase 3

Completed

Conditions: Early Parkinson Disease (Early PD)

Interventions: Drug: Pramipexol Immediate Release
Drug: Pramipexol Extended Release
Drug: Placebo

Registration Number: NCT00479401

Lead Sponsor: Boehringer Ingelheim

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 539

Inclusion Criteria

Male or female patient with idiopathic Parkinsons disease (PD) confirmed by at least two of the following signs: resting tremor, bradykinesia, rigidity.
Parkinsons disease diagnosed within 5 years.
Patients 30 years of age or older at the time of diagnosis.
Modified Hoehn and Yahr stage of 1 to 3.
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

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).
Dementia, as defined by a Mini-Mental State Exam score < 24 at screening visit
Any psychiatric disorder according to Diagnostic and Statistical Manual of Mental Disorders 4th (DSM-IV)
History of psychosis
Clinically significant electrocardiogram (ECG) abnormalities at screening visit
Clinically significant hypotension
Malignant melanoma or history of previously treated malignant melanoma
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
Pregnancy
Sexually active female of childbearing potential not using a medically approved method of birth control
Serum levels of Aspartate Aminotransferase (AST) , Alanine Aminotransferase (ALT), alkaline phosphatases or bilirubin > 2 Upper Limit of Normal (ULN)
Patients with a creatinine clearance < 50 mL/min
Any dopamine agonist (including pramipexole) within 4 weeks prior to baseline visit, or L-Dopa within 8 weeks prior to baseline visit.
Total cumulative duration of prior exposure to Levodopa of more than 3 months.
Any medication (including intra-muscular formulations) with central dopaminergic antagonist activity within 4 weeks prior to the baseline visit
Any of the following drugs within 4 weeks prior to the baseline visit: methylphenidate, cinnarizine, amphetamines.
Flunarizine within 3 months prior to baseline visit
Known hypersensitivity to Pramipexole or its excipients
Drug abuse (including alcohol), according to Investigators judgement, within 2 years prior to screening.
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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pramipexole Immediate Release (PPX IR)	Pramipexol Immediate Release	-
Pramipexole Extended Release (PPX ER)	Pramipexol Extended Release	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score	baseline and after 33 weeks treatment	Activities of daily living are scored from 0-52 in UPDRS II, result of motor examination scored 0-108 in UPDRS III. A decrease in the score means improvement.

Secondary Outcome Measures

Name	Time	Method
Percentage of Responders on the Clinical Global Impressions of Improvement (CGI-I) Scale	after 18 weeks of treatment compared to baseline	Clinicians evaluation in a rating scale of 7 steps, 1 meaning very much improved to 7 meaning very much worse. Responders are the patients with 'much improved' and 'very much improved' on the scale
UPDRS II+III Responder Rate (at Least 20% Improvement)	after 33 weeks treatment	Responders are defined as at least 20% decrease in the UPDRS II+III score. UPDRS II+III ranges 0-160 scores from best to worse.
Parkinson's Disease Sleep Scale (PDSS)	after 33 weeks treatment	PDSS is a self-rated instrument addressing 15 commonly reported symptoms associated with sleep disturbance on 15 visual analogue scales (VAS: 0 to 10 cm) each ranging from worst score ('awful or always' at the left extremity to the best score ('excellent or never' at the right extremity) An increase in the score means improvement. Worst possible score 0, best score 150)
Change From Baseline in Parkinson's Disease Quality of Life Questionnaire Total Score	after 33 weeks treatment	The PDQ-39 is a self-administered questionnaire which comprises 39 items addressing 8 domains of health which patients consider to be adversely affected by the disease. Higher scores are consistently associated with more severe symptoms of the disease such as tremor and stiffness, while lower scores indicate a better perceived health status. The 8 domains include: * mobility (e.g. fear of falling when walking): 10 items * activities of daily living (e.g. difficulty cutting food): 6 items * emotional well-being (e.g. feelings of isolation): 6 items * stigma (e.g. social embarrassment): 4 items * social support: 3 items * cognition: 4 items * communication: 3 items * bodily discomfort: 3 items. A total score is calculated by summing the responses to the 39 individual items and the total ranges from 0 (no problem at all) to 156 (maximum level of problem). A negative change in the total score indicates improvement.
Patients Who Started to Use L-Dopa Rescue Medication	from trial start on to any time before final assessment of the patient, up to 33 weeks	L-dopa could be introduced as rescue medication based upon the clinical judgement of the investigator. descriptive on the Full Analysis Set (FAS) population
Possible Clinically Significant Abnormal Laboratory Parameters	baseline and after 33 weeks of treatment	The significant abnormality of values was based on standard criteria defined in appendix 16.1.10, LISTING 4 Criteria for clinically significant abnormalities based on normalized laboratory values.
Percentage of Responders on the Patients Global Impressions of Improvement (PGI-I) Scale	after 18 weeks of treatment compared to baseline	Patient rated evaluation of the PD symptoms on a rating scale of 7 steps, 1 meaning very much better to 7 meaning very much worse. Responders are the patients with 'much better' and 'very much better' on the score.
UPDRS Part II Total Score	after 33 weeks treatment	UPDRS II evaluates activities of daily living in a score 0-52. Decrease of the score means improvement
Likert Scale for Pain Related to PD	after 33 weeks treatment	Patient assessed 11 units on a scale from 'no pain' to 'unbearable pain'. Decrease of the score means improvement
UPDRS Part I Change From Baseline	baseline and after 33 weeks treatment	UPDRS I evaluates mentation behaviour and mood with a total score of 0-16. Decrease in the scores means improvement
UPDRS Part III Total Score	after 33 weeks treatment	UPDRS III is the result of a motor examination with the scores 0-108. A decrease in the scores means improvement
Beck's Depression Inventory Version I A	after 33 weeks treatment	The Beck's Depression Inventory (BDI) is a 21-item self-rating scale that was originally designed as an instrument to assess the intensity of depressive symptoms (sadness, pessimism, sense of failure, dissatisfaction, guilt, expectation of punishment, dislike of self, self-accusation, suicidal ideation, episodes of crying, irritability, social withdrawal, indecisiveness, changes in body image, retardation, insomnia, fatigability, loss of appetite and weight, somatic preoccupation, low level of energy). Each item is scored from 0 (absent) to 3 (severe). The patients select the score which best describes their status in the last 7 days. Since its introduction in 1961, its use has been extended (also to PD patients) and today it is used also as a screening instrument as well as an outcome measure in depression treatment trials. The total score sums the 21 individual items yielding a score that can range from zero (minimal depression) to 63 (severe depression).
Number of Patients With Treatment Emergent Abnormal Behaviour as Indicated by the Modified Minnesota Impulsive Disorders Interview (mMIDI Questionnaire)	from trial start on to any time before final assessment of the patient, up to 33 weeks	mMIDI is a semi-structured clinical interview to assess pathological gambling (12 questions, positive screen if patient answers 'yes' to question 1 and to at least 5 of the rest of the questions), compulsive buying (9 questions from 1a to 4c, positive screen if the patient answers 'yes' to 1a, 2a, 3a, and 4a) and compulsive sexual behaviour (4 questions, positive screen if patient answers 'yes' to question 1,2,3, or 4).
Change From Baseline in European Quality of Life Visual Analog Scale	after 33 weeks treatment	European Quality of Life Visual Analog Scale (EQ-5D VAS) is a 20 centimeter vertical analog scale assessing the patient's general health status with scores ranging from 0 (worst imaginable health) to 100 (perfect health). A positive change in the scale indicates improvement in health status.
Clinical Relevant Abnormal Findings in Vital Signs and Physical Examination as Reported in Adverse Events	baseline and after 33 weeks of treatment

Trial Locations

Locations (95): 248.524.36008 Boehringer Ingelheim Investigational Site
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Miskolc, Hungary
248.524.91010 Boehringer Ingelheim Investigational Site
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Hyderabad, India
248.524.91001 Boehringer Ingelheim Investigational Site
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Karnataka, India
248.524.91011 Boehringer Ingelheim Investigational Site
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Pune, India
248.524.81009 Boehringer Ingelheim Investigational Site
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Morioka, Iwate, Japan
248.524.88601 Boehringer Ingelheim Investigational Site
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Taipei, Taiwan
248.524.38001 Boehringer Ingelheim Investigational Site
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Lvov, Ukraine
248.524.01018 Boehringer Ingelheim Investigational Site
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Gilbert, Arizona, United States
248.524.01010 Boehringer Ingelheim Investigational Site
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Boca Raton, Florida, United States
248.524.01014 Boehringer Ingelheim Investigational Site
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Augusta, Georgia, United States
248.524.01017 Boehringer Ingelheim Investigational Site
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Hattiesburg, Mississippi, United States
248.524.01002 Boehringer Ingelheim Investigational Site
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Dallas, Texas, United States
248.524.01009 Boehringer Ingelheim Investigational Site
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Burlington, Vermont, United States
248.524.01012 Boehringer Ingelheim Investigational Site
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Chicago, Illinois, United States
248.524.01004 Boehringer Ingelheim Investigational Site
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Sun City, Arizona, United States
248.524.01016 Boehringer Ingelheim Investigational Site
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La Jolla, California, United States
248.524.01013 Boehringer Ingelheim Investigational Site
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Oxnard, California, United States
248.524.01001 Boehringer Ingelheim Investigational Site
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Kansas City, Kansas, United States
248.524.01007 Boehringer Ingelheim Investigational Site
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Elkridge, Maryland, United States
248.524.01003 Boehringer Ingelheim Investigational Site
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Midvale, Utah, United States
248.524.01015 Boehringer Ingelheim Investigational Site
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Southfield, Michigan, United States
248.524.01005 Boehringer Ingelheim Investigational Site
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Commack, New York, United States
248.524.54007 Boehringer Ingelheim Investigational Site
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Capital Federal, Argentina
248.524.54008 Instituto de Neurociencias de Buenos Aires
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Capital Federal, Argentina
248.524.49003 Boehringer Ingelheim Investigational Site
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Bochum, Germany
248.524.54009 Boehringer Ingelheim Investigational Site
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Capital Federal, Argentina
248.524.42003 Boehringer Ingelheim Investigational Site
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Pardubice, Czech Republic
248.524.42001 Boehringer Ingelheim Investigational Site
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Praha, Czech Republic
248.524.42002 Boehringer Ingelheim Investigational Site
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Rychnov nad Kneznou, Czech Republic
248.524.35802 Boehringer Ingelheim Investigational Site
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Tampere, Finland
248.524.36007 Boehringer Ingelheim Investigational Site
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Eger, Hungary
248.524.36005 Boehringer Ingelheim Investigational Site
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Györ, Hungary
248.524.49005 Boehringer Ingelheim Investigational Site
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Marburg, Germany
248.524.49008 Boehringer Ingelheim Investigational Site
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Bremerhaven, Germany
248.524.49011 Boehringer Ingelheim Investigational Site
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Bochum, Germany
248.524.49006 Boehringer Ingelheim Investigational Site
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Dresden, Germany
248.524.36004 Boehringer Ingelheim Investigational Site
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Sopron, Hungary
248.524.36001 Boehringer Ingelheim Investigational Site
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Szeged, Hungary
248.524.36002 Boehringer Ingelheim Investigational Site
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Zalaegerszeg, Hungary
248.524.91005 Boehringer Ingelheim Investigational Site
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Maharashtra, India
248.524.81011 Boehringer Ingelheim Investigational Site
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Fujisawa, Kanagawa, Japan
248.524.81013 Boehringer Ingelheim Investigational Site
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Fukuoka, Fukuoka, Japan
248.524.81003 Boehringer Ingelheim Investigational Site
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Kodaira, Tokyo, Japan
248.524.81006 Boehringer Ingelheim Investigational Site
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Ota-ku, Tokyo, Japan
248.524.81004 Boehringer Ingelheim Investigational Site
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Sagamihara, Kanagawa, Japan
248.524.60004 Boehringer Ingelheim Investigational Site
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Kuala Terengganu, Malaysia
248.524.07003 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
248.524.07004 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
248.524.42103 Boehringer Ingelheim Investigational Site
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Dubnica nad Vahom, Slovakia
248.524.42101 Boehringer Ingelheim Investigational Site
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Trnava, Slovakia
248.524.07005 Boehringer Ingelheim Investigational Site
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St. Petersburg, Russian Federation
248.524.07006 Boehringer Ingelheim Investigational Site
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St. Petersburg, Russian Federation
248.524.88603 Boehringer Ingelheim Investigational Site
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Kaohsiung, Taiwan
248.524.38006 Boehringer Ingelheim Investigational Site
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Zaporozhye, Ukraine
248.524.88605 Boehringer Ingelheim Investigational Site
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Taichung, Taiwan
248.524.38004 Boehringer Ingelheim Investigational Site
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Zaporizhzhya, Ukraine
248.524.49001 Boehringer Ingelheim Investigational Site
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Kassel, Germany
248.524.49007 Boehringer Ingelheim Investigational Site
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Göttingen, Germany
248.524.49004 Boehringer Ingelheim Investigational Site
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Leipzig, Germany
248.524.01008 Boehringer Ingelheim Investigational Site
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Danbury, Connecticut, United States
248.524.54002 Boehringer Ingelheim Investigational Site
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Capital Federal, Argentina
248.524.54001 Boehringer Ingelheim Investigational Site
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Capital Federal, Argentina
248.524.54003 Boehringer Ingelheim Investigational Site
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Capital Federal, Argentina
248.524.43001 Boehringer Ingelheim Investigational Site
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Innsbruck, Austria
248.524.54006 Boehringer Ingelheim Investigational Site
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Mar del Plata, Argentina
248.524.43004 Boehringer Ingelheim Investigational Site
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Wien, Austria
248.524.54004 Boehringer Ingelheim Investigational Site
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Santa Fe, Argentina
248.524.42004 Boehringer Ingelheim Investigational Site
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Olomouc, Czech Republic
248.524.35801 Boehringer Ingelheim Investigational Site
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Oulu, Finland
248.524.35803 Boehringer Ingelheim Investigational Site
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Hyvinkää, Finland
248.524.49002 Boehringer Ingelheim Investigational Site
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Berlin, Germany
248.524.36006 Boehringer Ingelheim Investigational Site
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Szeged, Hungary
248.524.91002 Boehringer Ingelheim Investigational Site
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Chennai, India
248.524.91009 Boehringer Ingelheim Investigational Site
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Hyderabad, India
248.524.81010 Boehringer Ingelheim Investigational Site
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Aomori, Aomori, Japan
248.524.91007 Boehringer Ingelheim Investigational Site
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Maharashtra, India
248.524.91006 Boehringer Ingelheim Investigational Site
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New Delhi, India
248.524.81001 Boehringer Ingelheim Investigational Site
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Bunkyo-ku, Tokyo, Japan
248.524.81005 Boehringer Ingelheim Investigational Site
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Fuchu, Tokyo, Japan
248.524.81015 Boehringer Ingelheim Investigational Site
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Iwamizawa,Hokkaido, Japan
248.524.81008 Boehringer Ingelheim Investigational Site
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Okayama, Okayama, Japan
248.524.81012 Boehringer Ingelheim Investigational Site
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Shiroishi, Miyagi, Japan
248.524.81014 Boehringer Ingelheim Investigational Site
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Kyoto, Kyoto, Japan
248.524.81002 Boehringer Ingelheim Investigational Site
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Takamatsu, Kagawa, Japan
248.524.60001 Boehringer Ingelheim Investigational Site
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Kuala Lumpur, Malaysia
248.524.81007 Boehringer Ingelheim Investigational Site
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Shimogyo-ku, Kyoto, Kyoto, Japan
248.524.60002 Boehringer Ingelheim Investigational Site
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Pulau Pinang, Malaysia
248.524.07001 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
248.524.07002 Boehringer Ingelheim Investigational Site
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Moscow, Russian Federation
248.524.88602 Boehringer Ingelheim Investigational Site
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Taoyuan, Taiwan
248.524.38005 Boehringer Ingelheim Investigational Site
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Kiev, Ukraine
248.524.38002 Boehringer Ingelheim Investigational Site
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Uzhgorod, Ukraine
248.524.38003 Boehringer Ingelheim Investigational Site
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Vinnytzya, Ukraine
248.524.36003 Boehringer Ingelheim Investigational Site
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Szombathely, Hungary
248.524.91004 Boehringer Ingelheim Investigational Site
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New Delhi, India