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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

Primary Purpose

Parkinson Disease

Status

Completed

Phase

Phase 2

Locations

Japan

Study Type

Interventional

Intervention

Pramipexole Immediate Release

Pramipexole Extended Release

About this trial

This is an interventional treatment trial for Parkinson Disease

Eligibility Criteria

1 Year - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

Male or female patients with diagnosis of PD including juvenile Parkinsonism, in whom the onset began at the age of forty or younger.
Patients with a modified Hoehn and Yahr scale of II to IV at "on" time.
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).
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

Atypical parkinsonian syndromes due to drugs, metabolic disorders, encephalitis or degenerative diseases.
Dementia, as defined by a Mini-Mental State Examination (MMSE) score <24 at screening visit.
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.
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).
Clinically significant ECG abnormalities at screening visit, according to investigator's judgement.
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.
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.
Pregnancy (to be excluded by serum pregnancy test at screening visit) or breast-feeding.
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.
Serum levels of AST, ALT, alkaline phosphatases or bilirubin >2 upper limits of normal .
Patients with a creatinine clearance <50 mL/min
Patients with a complication or signs of malignant tumours or those within 5 years after the treatment.

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Pramipexole Extended Release

Pramipexole Immediate Release

Arm 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

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

Outcomes

Primary Outcome Measures

Percentage of Participants Who Experienced Adverse Events

An adverse event is defined as any untoward medical occurrence

Secondary Outcome Measures

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

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).

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.

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.

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

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.

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.

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)

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)

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

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.

Change From Baseline in UPDRS Part III Score

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

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

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

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.

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.

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

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.

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)

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)

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).

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

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

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

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

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

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

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

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.

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

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.

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

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

Full Information

NCT ID

NCT00560508

First Posted

November 16, 2007

Last Updated

July 29, 2014

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT00560508

Brief Title

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

2. Study Status

Record Verification Date

July 2014

Overall Recruitment Status

Completed

Study Start Date

November 2007 (undefined)

Primary Completion Date

November 2009 (Actual)

Study Completion Date

undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

112 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Pramipexole Extended Release

Arm Type

Experimental

Arm Description

Arm Title

Pramipexole Immediate Release

Arm Type

Active Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Pramipexole Immediate Release

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Pramipexole Extended Release

Intervention Description

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

Primary Outcome Measure Information:

Title

Percentage of Participants Who Experienced Adverse Events

Description

An adverse event is defined as any untoward medical occurrence

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

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

Description

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