Clinical trial NCT00560508: A 12-week Study of Pramipexole Extended Release (ER) in Patients With Parkinson's Disease (PD), Followed by a 52-week Long-term Treatment Period
Official title: A Double-blind, Double-dummy, Randomised, Parallel-group Study to Investigate the Safety, Tolerability, Trough Plasma Concentration, and Efficacy of Pramipexole ER Versus Pramipexole Immediate Release (IR) Administered Orally for 12 Weeks in Patients With Parkinson's Disease (PD) on L-dopa Therapy, Followed by a 52-week Open-label Long-term Treatment Period to Evaluate the Long-term Safety and Efficacy of Pramipexole ER
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Parkinson Disease
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2007-11-19
Enrollment: 112
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this trial is to investigate the safety, tolerability, trough plasma concentration, and efficacy of pramipexole ER in comparison with those of pramipexole IR administrated orally for 12 weeks in patients with PD on levodopa (L-DOPA) therapy (the double-blind period). The double-blind period will be followed by the open-label 52 week administration of pramipexole ER to evaluate the long term safety and efficacy (the open-label period).


Eligibility criteria: Inclusion criteria

1. Male or female patients with diagnosis of PD including juvenile Parkinsonism, in whom the onset began at the age of forty or younger.
2. Patients with a modified Hoehn and Yahr scale of II to IV at "on" time.
3. Patients who have received an individual dosage of L-DOPA (either standard L-DOPA or L-DOPA with dopa-decarboxylase inhibitor) at a stable dose for at least 4 weeks before the baseline visit (Visit 2).
4. Patients who exhibit any therapeutically problematic issues or status based on L-DOPA therapy:

   * wearing-off phenomena
   * no on /delayed on
   * dystonia at off time
   * on-off phenomena
   * freezing phenomena at off time
   * the sub-optimal dose of L-DOPA had been administered due to side effects (such as dyskinesia), or therapeutical strategy

Exclusion criteria

1. Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases.
2. Dementia, as defined by a Mini-Mental State Examination (MMSE) score \<24 at screening visit.
3. Any psychiatric disorder according to DSM-IV criteria that could prevent compliance or completion of the trial and/or put the patient at risk if he/she takes part in the trial.
4. History of psychosis, except history of drug induced hallucinations (provided the investigator considers that participation in the trial would not represent a significant risk for the patient).
5. Clinically significant ECG abnormalities at screening visit, according to investigator's judgement.
6. Clinically significant hypotension or symptomatic orthostatic hypotension (i.e., clinical symptoms of orthostatic hypotension such as dizziness postural etc associated with a decline \>=20 mmHg in systolic blood pressure and a decline \>=10 mmHg in diastolic blood pressure, at one minute after standing compared with the previous supine systolic and diastolic blood pressure obtained after 5 minutes of quiet rest) either at screening visit or at baseline visit.
7. Any other clinically significant disease, whether treated or not, that could put the patient at risk or could prevent compliance or completion of the trial.
8. Pregnancy (to be excluded by serum pregnancy test at screening visit) or breast-feeding.
9. Sexually active female of childbearing potential not using a medically approved method of birth control within one month before to the screening visit and throughout the trial period.
10. Serum levels of AST, ALT, alkaline phosphatases or bilirubin \>2 upper limits of normal .
11. Patients with a creatinine clearance \<50 mL/min
12. Patients with a complication or signs of malignant tumours or those within 5 years after the treatment.

Primary outcomes:
measure: Percentage of Participants Who Experienced Adverse Events
timeFrame: 12 weeks
Secondary outcomes:
measure: Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score
timeFrame: baseline and after 12 weeks treatment
measure: Change From Baseline in Percentage Off-time
timeFrame: baseline and after 12 weeks treatment
measure: Change From Baseline in Percentage On-time Without Dyskinesia
timeFrame: baseline and after 12 weeks treatment
measure: Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia
timeFrame: baseline and after 12 weeks treatment
measure: Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia
timeFrame: baseline and after 12 weeks treatment
measure: Change From Baseline in Percentage On-time With Troublesome Dyskinesia
timeFrame: baseline and after 12 weeks treatment
measure: Responder Rate For Clinical Global Impression of Improvement (CGI-I)
timeFrame: baseline and after 12 weeks treatment
measure: Responder Rate For Patient Global Impression of Improvement (PGI-I)
timeFrame: baseline and after 12 weeks treatment
measure: Change From Baseline in UPDRS Part I Score
timeFrame: baseline and after 12 weeks treatment
measure: Change From Baseline in UPDRS Part II Score
timeFrame: baseline and after 12 weeks treatment
measure: Change From Baseline in UPDRS Part III Score
timeFrame: baseline and after 12 weeks treatment
measure: Change From Baseline in UPDRS Part IV Score
timeFrame: baseline and after 12 weeks treatment
measure: UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement)
timeFrame: baseline and after 12 weeks treatment
measure: Change From Baseline in L-dopa Daily Dose
timeFrame: baseline and after 12 weeks treatment
measure: Trough Plasma Concentration at Steady State
timeFrame: at Visit 8 after pramipexole ER 4.5mg and IR 4.5mg treatment
measure: Dose Proportionality of Trough Plasma Concentration at Steady State After Pramipexole ER Treatment
timeFrame: from Visit 1 to Visit 8 after pramipexole ER
measure: Change From End of Double-Blind Period in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Dose Adjustment Phase)
timeFrame: Week 12 to Week 16
measure: Percentage of Patients With no Worsening of UPDRS Parts II+III Total Score by More Than 15% From Week 12 to Week 16 (Open-label: Dose Adjustment Phase)
timeFrame: Week 12 to Week 16
measure: Clinical Global Impression of Improvement (CGI-I) at Week 16 Compared to Patient's CGI-I Status at Week 12 (Open-label: Dose Adjustment Phase)
timeFrame: Week 12 to Week 16
measure: Patient Global Impression of Improvement (PGI-I) at Week 16 Compared to Patient's PGI-I Status at Week 12 (Open-label: Dose Adjustment Phase)
timeFrame: Week 12 to Week 16
measure: Change From Baseline in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Maintenance Phase)
timeFrame: Baseline and after 64 weeks treatment
measure: UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) (Open-label: Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
measure: Change From Baseline in Percentage Off-time (Open-label: Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
measure: Change From Baseline in Percentage On-time Without Dyskinesia (Open-label: Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
measure: Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia (Open-label Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
measure: Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia (Open-label Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
measure: Change From Baseline in Percentage On-time With Troublesome Dyskinesia (Open-label Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
measure: Change From Baseline in L-dopa Daily Dose (Open-label Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
measure: Change From Baseline in UPDRS Part I Score (Open-label: Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
measure: Change From Baseline in UPDRS Part II Score (Open-label: Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
measure: Change From Baseline in UPDRS Part III Score (Open-label: Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
measure: Change From Baseline in UPDRS Part IV Score (Open-label: Maintenance Phase)
timeFrame: baseline and after 64 weeks treatment
Other outcomes:
Locations:
city: Akashi, Hyogo
country: Japan
facility: 248.610.019 Boehringer Ingelheim Investigational Site
city: Akita, Akita
country: Japan
facility: 248.610.020 Boehringer Ingelheim Investigational Site
city: Aomori, Aomori
country: Japan
facility: 248.610.006 Boehringer Ingelheim Investigational Site
city: Asahikawa, Hokkaido
country: Japan
facility: 248.610.017 Boehringer Ingelheim Investigational Site
city: Asahikawa, Hokkaido
country: Japan
facility: 248.610.018 Boehringer Ingelheim Investigational Site
city: Bunkyo-ku, Tokyo
country: Japan
facility: 248.610.001 Boehringer Ingelheim Investigational Site
city: Fuchu, Tokyo
country: Japan
facility: 248.610.014 Boehringer Ingelheim Investigational Site
city: Fukuoka, Fukuoka
country: Japan
facility: 248.610.011 Boehringer Ingelheim Investigational Site
city: Iwamizawa,Hokkaido
country: Japan
facility: 248.610.015 Boehringer Ingelheim Investigational Site
city: Kodaira, Tokyo
country: Japan
facility: 248.610.003 Boehringer Ingelheim Investigational Site
city: Kyoto, Kyoto
country: Japan
facility: 248.610.008 Boehringer Ingelheim Investigational Site
city: Kyoto, Kyoto
country: Japan
facility: 248.610.021 Boehringer Ingelheim Investigational Site
city: Morioka, Iwate
country: Japan
facility: 248.610.010 Boehringer Ingelheim Investigational Site
city: Okayama, Okayama
country: Japan
facility: 248.610.005 Boehringer Ingelheim Investigational Site
city: Osaka, Osaka
country: Japan
facility: 248.610.012 Boehringer Ingelheim Investigational Site
city: Sagamihara, Kanagawa
country: Japan
facility: 248.610.004 Boehringer Ingelheim Investigational Site
city: Shimogyo-ku, Kyoto, Kyoto
country: Japan
facility: 248.610.009 Boehringer Ingelheim Investigational Site
city: Shiroishi, Miyagi
country: Japan
facility: 248.610.007 Boehringer Ingelheim Investigational Site
city: Takamatsu, Kagawa
country: Japan
facility: 248.610.002 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: