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

Boehringer Ingelheim112 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

112

Conditions

Parkinson Disease

Interventions

Pramipexole Immediate ReleaseDRUG

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

Pramipexole Extended ReleaseDRUG

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

Eligibility

Sex: ALLMin age: 1 Year

Medical Language ↔ Plain English

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.

Locations (19)

248.610.019 Boehringer Ingelheim Investigational Site

Akashi, Hyogo, Japan

248.610.020 Boehringer Ingelheim Investigational Site

Outcomes

Primary Outcomes

Percentage of Participants Who Experienced Adverse Events

An adverse event is defined as any untoward medical occurrence

Time frame: 12 weeks

Secondary Outcomes

Change From Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) Parts II+III Total Score

UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms

Time frame: baseline and after 12 weeks treatment

Change From Baseline in Percentage Off-time

Percentage off-time during waking hours in the last two days based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). Off-time describes a period when the patient experiences increased parkinsonian symptoms (e.g. immobility or inability to move with ease).

Time frame: baseline and after 12 weeks treatment

Change From Baseline in Percentage On-time Without Dyskinesia

Percentage on-time without dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

Time frame: baseline and after 12 weeks treatment

Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia

Percentage on-time with non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0(worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

Time frame: baseline and after 12 weeks treatment

Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia

Data from ClinicalTrials.gov

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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

...and 9 more locations

Percentage on-time without dyskinesia or non-troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (worst case) to 100 (best case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

Time frame: baseline and after 12 weeks treatment

Change From Baseline in Percentage On-time With Troublesome Dyskinesia

Percentage on-time with troublesome dyskinesia during waking hours in the last two days based on patient diary data, percentage ranging from 0 (best case) to 100 (worst case). On-time describes a period when the patient has no symptoms of off-time and is not asleep.

Time frame: baseline and after 12 weeks treatment

Responder Rate For Clinical Global Impression of Improvement (CGI-I)

CGI-I scores ranging from '1' (very much improved) to '7' (very much worse), CGI-I responder have scoring of 1 or 2 (at least much improved)

Time frame: baseline and after 12 weeks treatment

Responder Rate For Patient Global Impression of Improvement (PGI-I)

PGI-I scores ranging from '1' (very much better) to '7' (very much worse), PGI-I responder have scoring of 1 or 2 (at least much better)

Time frame: baseline and after 12 weeks treatment

Change From Baseline in UPDRS Part I Score

UPDRS Part I ranging from 0 (normal) to 16 (severe). UPDRS Part I measures Mentation, Behavior and Mood

Time frame: baseline and after 12 weeks treatment

Change From Baseline in UPDRS Part II Score

UPDRS Part II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS Part II at on and UPDRS Part II at off-period for each of the 13 activities.

Time frame: baseline and after 12 weeks treatment

Change From Baseline in UPDRS Part III Score

UPDRS Part III ranging from 0 (normal) to 108 (severe). UPDRS Part III measures motor symptoms

Time frame: baseline and after 12 weeks treatment

Change From Baseline in UPDRS Part IV Score

UPDRS Part IV ranging from 0 (normal) to 23 (severe). UPDRS Part IV measures complications of therapy

Time frame: baseline and after 12 weeks treatment

UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement)

Responders are defined as at least 20% decrease in the UPDRS Parts II+III Total Score ranges 0-160 scores from best to worse

Time frame: baseline and after 12 weeks treatment

Change From Baseline in L-dopa Daily Dose

The L-dopa daily dose was recorded in the electronic case report form (eCRF) at each trial visit.

Time frame: baseline and after 12 weeks treatment

Trough Plasma Concentration at Steady State

Geometric mean (gMean) was calculated for trough plasma concentrations of pramipexole at steady state after administration of pramipexole IR 4.5mg and pramipexole ER 4.5mg.

Time frame: 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

Dose proportionality of trough plasma concentrations at steady state is explored by using the power model that described the functional relationship between the dose and plasma concentration

Time frame: 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)

UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms. Least square means and standard errors presented are from ANCOVA with factors treatment and covariate baseline.

Time frame: 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)

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)

Time frame: 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)

Clinical Global Impression of Improvement (CGI-I) at week 16 compared to patient's CGI-I status at week 12. CGI-I scores ranging from '1' (very much improved) to '7' (very much worse)

Time frame: 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)

Patient Global Impression of Improvement (PGI-I) at week 16 compared to patient's PGI-I status at week 12. PGI-I scores ranging from '1' (very much better) to '7' (very much worse).

Time frame: 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)

UPDRS II+III ranging from 0 point(normal) to 160 point (severe). UPDRS part II measures activities of daily living, part III measures motor symptoms

Time frame: Baseline and after 64 weeks treatment

UPDRS Parts II+III Total Score Responder Rate (at Least 20% Improvement) (Open-label: Maintenance Phase)

Responders are defined as at least 20% decrease in the UPDRS Parts II+III Total Score ranges 0-160 scores from best to worse

Time frame: baseline and after 64 weeks treatment

Change From Baseline in Percentage Off-time (Open-label: Maintenance Phase)

Time frame: baseline and after 64 weeks treatment

Change From Baseline in Percentage On-time Without Dyskinesia (Open-label: Maintenance Phase)

Time frame: baseline and after 64 weeks treatment

Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia (Open-label Maintenance Phase)

Time frame: baseline and after 64 weeks treatment

Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia (Open-label Maintenance Phase)

Time frame: baseline and after 64 weeks treatment

Change From Baseline in Percentage On-time With Troublesome Dyskinesia (Open-label Maintenance Phase)

Time frame: baseline and after 64 weeks treatment

Change From Baseline in L-dopa Daily Dose (Open-label Maintenance Phase)

The L-dopa daily dose was recorded in the electronic case report form (eCRF) at each trial visit.

Time frame: baseline and after 64 weeks treatment

Change From Baseline in UPDRS Part I Score (Open-label: Maintenance Phase)

UPDRS Part I ranging from 0 (normal) to 16 (severe). UPDRS Part I measures Mentation, Behavior and Mood

Time frame: baseline and after 64 weeks treatment

Change From Baseline in UPDRS Part II Score (Open-label: Maintenance Phase)

UPDRS Part II ranging from 0 (normal) to 52 (severe). UPDRS Part II is calculated as the average of UPDRS Part II at on and UPDRS Part II at off-period for each of the 13 activities.

Time frame: baseline and after 64 weeks treatment

Change From Baseline in UPDRS Part III Score (Open-label: Maintenance Phase)

UPDRS Part III ranging from 0 (normal) to 108 (severe). UPDRS Part III measures motor symptoms

Time frame: baseline and after 64 weeks treatment

Change From Baseline in UPDRS Part IV Score (Open-label: Maintenance Phase)

UPDRS Part IV ranging from 0 (normal) to 23 (severe). UPDRS Part IV measures complications of therapy

Time frame: baseline and after 64 weeks treatment