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

Parkinson Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00560508
• Other study ID #: 248.610
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: November 16, 2007
• Last updated: July 29, 2014
• Start date: November 2007

Study information

• Verified date: July 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• Pramipexole Immediate Release
titrated as individually needed (0.25 mg - 4.5 mg daily)
• Pramipexole Extended Release
titration as individually needed (0.375 mg -4.5 mg daily)

Locations

Country	Name	City	State
Japan	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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Experienced Adverse Events	An adverse event is defined as any untoward medical occurrence	12 weeks	No
Secondary	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	baseline and after 12 weeks treatment	No
Secondary	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).	baseline and after 12 weeks treatment	No
Secondary	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.	baseline and after 12 weeks treatment	No
Secondary	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.	baseline and after 12 weeks treatment	No
Secondary	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.	baseline and after 12 weeks treatment	No
Secondary	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.	baseline and after 12 weeks treatment	No
Secondary	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)	baseline and after 12 weeks treatment	No
Secondary	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)	baseline and after 12 weeks treatment	No
Secondary	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	baseline and after 12 weeks treatment	No
Secondary	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.	baseline and after 12 weeks treatment	No
Secondary	Change From Baseline in UPDRS Part III Score	UPDRS Part III ranging from 0 (normal) to 108 (severe). UPDRS Part III measures motor symptoms	baseline and after 12 weeks treatment	No
Secondary	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	baseline and after 12 weeks treatment	No
Secondary	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	baseline and after 12 weeks treatment	No
Secondary	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.	baseline and after 12 weeks treatment	No
Secondary	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.	at Visit 8 after pramipexole ER 4.5mg and IR 4.5mg treatment	No
Secondary	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	from Visit 1 to Visit 8 after pramipexole ER	No
Secondary	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.	Week 12 to Week 16	No
Secondary	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)	Week 12 to Week 16	No
Secondary	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)	Week 12 to Week 16	No
Secondary	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).	Week 12 to Week 16	No
Secondary	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	Baseline and after 64 weeks treatment	No
Secondary	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	baseline and after 64 weeks treatment	No
Secondary	Change From Baseline in Percentage Off-time (Open-label: Maintenance Phase)	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).	baseline and after 64 weeks treatment	No
Secondary	Change From Baseline in Percentage On-time Without Dyskinesia (Open-label: Maintenance Phase)	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.	baseline and after 64 weeks treatment	No
Secondary	Change From Baseline in Percentage On-time With Non-troublesome Dyskinesia (Open-label Maintenance Phase)	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.	baseline and after 64 weeks treatment	No
Secondary	Change From Baseline in Percentage On-time Without Dyskinesia or With Non-troublesome Dyskinesia (Open-label Maintenance Phase)	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.	baseline and after 64 weeks treatment	No
Secondary	Change From Baseline in Percentage On-time With Troublesome Dyskinesia (Open-label Maintenance Phase)	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.	baseline and after 64 weeks treatment	No
Secondary	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.	baseline and after 64 weeks treatment	No
Secondary	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	baseline and after 64 weeks treatment	No
Secondary	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.	baseline and after 64 weeks treatment	No
Secondary	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	baseline and after 64 weeks treatment	No
Secondary	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	baseline and after 64 weeks treatment	No

External Links

•   Link