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

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

Sponsors

Lead sponsor: Boehringer Ingelheim

Source Boehringer Ingelheim
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).

Overall Status Completed
Start Date November 2007
Primary Completion Date November 2009
Phase Phase 2/Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Percentage of Participants Who Experienced Adverse Events 12 weeks
Secondary Outcome
Measure Time Frame
Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score baseline and after 12 weeks treatment
Change From Baseline in Percentage Off-time baseline and after 12 weeks treatment
Change From Baseline in Percentage On-time Without Dyskinesia baseline and after 12 weeks treatment
Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia baseline and after 12 weeks treatment
Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia baseline and after 12 weeks treatment
Change From Baseline in Percentage On-time With Troublesome Dyskinesia baseline and after 12 weeks treatment
Responder Rate For Clinical Global Impression of Improvement (CGI-I) baseline and after 12 weeks treatment
Responder Rate For Patient Global Impression of Improvement (PGI-I) baseline and after 12 weeks treatment
Change From Baseline in UPDRS Part I Score baseline and after 12 weeks treatment
Change From Baseline in UPDRS Part II Score baseline and after 12 weeks treatment
Change From Baseline in UPDRS Part III Score baseline and after 12 weeks treatment
Change From Baseline in UPDRS Part IV Score baseline and after 12 weeks treatment
UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) baseline and after 12 weeks treatment
Change From Baseline in L-dopa Daily Dose baseline and after 12 weeks treatment
Trough Plasma Concentration at Steady State at Visit 8 after pramipexole ER 4.5mg and IR 4.5mg treatment
Dose Proportionality of Trough Plasma Concentration at Steady State After Pramipexole ER Treatment from Visit 1 to Visit 8 after pramipexole ER
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) Week 12 to Week 16
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) Week 12 to Week 16
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) Week 12 to Week 16
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) Week 12 to Week 16
Change From Baseline in UPDRS (Unified Parkinson's Disease Rating Scale) Parts II+III Total Score (Open-label: Maintenance Phase) Baseline and after 64 weeks treatment
UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) (Open-label: Maintenance Phase) baseline and after 64 weeks treatment
Change From Baseline in Percentage Off-time (Open-label: Maintenance Phase) baseline and after 64 weeks treatment
Change From Baseline in Percentage On-time Without Dyskinesia (Open-label: Maintenance Phase) baseline and after 64 weeks treatment
Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia (Open-label Maintenance Phase) baseline and after 64 weeks treatment
Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia (Open-label Maintenance Phase) baseline and after 64 weeks treatment
Change From Baseline in Percentage On-time With Troublesome Dyskinesia (Open-label Maintenance Phase) baseline and after 64 weeks treatment
Change From Baseline in L-dopa Daily Dose (Open-label Maintenance Phase) baseline and after 64 weeks treatment
Change From Baseline in UPDRS Part I Score (Open-label: Maintenance Phase) baseline and after 64 weeks treatment
Change From Baseline in UPDRS Part II Score (Open-label: Maintenance Phase) baseline and after 64 weeks treatment
Change From Baseline in UPDRS Part III Score (Open-label: Maintenance Phase) baseline and after 64 weeks treatment
Change From Baseline in UPDRS Part IV Score (Open-label: Maintenance Phase) baseline and after 64 weeks treatment
Enrollment 112
Condition
Intervention

Intervention type: Drug

Intervention name: Pramipexole Immediate Release

Description: titrated as individually needed (0.25 mg - 4.5 mg daily)

Arm group label: Pramipexole Immediate Release

Intervention type: Drug

Intervention name: Pramipexole Extended Release

Description: titration as individually needed (0.375 mg -4.5 mg daily)

Arm group label: Pramipexole Extended Release

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.

Gender: All

Minimum age: 1 Year

Maximum age: N/A

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Boehringer Ingelheim Study Chair Boehringer Ingelheim
Location
facility
248.610.019 Boehringer Ingelheim Investigational Site | Akashi, Hyogo, Japan
248.610.020 Boehringer Ingelheim Investigational Site | Akita, Akita, Japan
248.610.006 Boehringer Ingelheim Investigational Site | Aomori, Aomori, Japan
248.610.017 Boehringer Ingelheim Investigational Site | Asahikawa, Hokkaido, Japan
248.610.018 Boehringer Ingelheim Investigational Site | Asahikawa, Hokkaido, Japan
248.610.001 Boehringer Ingelheim Investigational Site | Bunkyo-ku, Tokyo, Japan
248.610.014 Boehringer Ingelheim Investigational Site | Fuchu, Tokyo, Japan
248.610.011 Boehringer Ingelheim Investigational Site | Fukuoka, Fukuoka, Japan
248.610.015 Boehringer Ingelheim Investigational Site | Iwamizawa,Hokkaido, Japan
248.610.003 Boehringer Ingelheim Investigational Site | Kodaira, Tokyo, Japan
248.610.008 Boehringer Ingelheim Investigational Site | Kyoto, Kyoto, Japan
248.610.021 Boehringer Ingelheim Investigational Site | Kyoto, Kyoto, Japan
248.610.010 Boehringer Ingelheim Investigational Site | Morioka, Iwate, Japan
248.610.005 Boehringer Ingelheim Investigational Site | Okayama, Okayama, Japan
248.610.012 Boehringer Ingelheim Investigational Site | Osaka, Osaka, Japan
248.610.004 Boehringer Ingelheim Investigational Site | Sagamihara, Kanagawa, Japan
248.610.009 Boehringer Ingelheim Investigational Site | Shimogyo-ku, Kyoto, Kyoto, Japan
248.610.007 Boehringer Ingelheim Investigational Site | Shiroishi, Miyagi, Japan
248.610.002 Boehringer Ingelheim Investigational Site | Takamatsu, Kagawa, Japan
Location Countries

Japan

Verification Date

July 2014

Responsible Party

Responsible party type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Pramipexole Extended Release

Arm group type: Experimental

Description: patient to receive a tablet containing 0.375 mg Pramipexole ER once a day plus containing 0.125 mg Pramipexole IR placebo twice a day -> a tablet containing 1.5 mg Pramipexole ER three times daily (TID) plus 0.5 mg Pramipexole IR placebo TID

Arm group label: Pramipexole Immediate Release

Arm group type: Active Comparator

Description: patient to receive a tablet containing 0.125 mg Pramipexole IR twice a day plus containing 0.375 mg Pramipexole ER placebo once a day -> a tablet containing 0.5 mg Pramipexole IR three times daily (TID) plus 1.5 mg Pramipexole ER placebo TID

Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov