Clinical Evaluation of Ropinirole Prolonged Release/Extended Release (PR/XR) Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease

NCT ID: NCT00823836

Last Updated: 2017-01-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 302 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2010-12-31

Brief Summary

To investigate the efficacy and the safety of ropinirole PR/XR tablets to ropinirole immediate release (IR) tablets with advanced Parkinson's disease in conjunction with L-dopa in a double-blind, parallel group comparison study.

Conditions

Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ropinirolePR-PR group

Group Type: EXPERIMENTAL

ropinirole PR/XR

Intervention Type: DRUG

Double-blind non-inferiority verification phase (24 weeks) At the baseline visit (Week 0), subjects who completed screening period will be randomised (1:1) to double-blind treatment with either ropinirole PR-PR group or ropinirole IR-PR group.

The subjects'dose will be titrated according to the recommended schedule to achieve an optimal therapeutic response (ropinirolePR/XR2-15 mg/day ,ropinirolIR0.75-15 mg/day).

Double-blind PR/XR switching phase (8 weeks) Ropinirole IR-PR subjects will be switched overnight to a similar dose of ropinirole PR/XR, while the remaining ropinirole PR-PR group will continue on the same dosage.

Double blind long-term treatment phase (22 weeks) The same dose level at the end of PR/XR switching phase will be continued till week 54 under blind.

Down titration phase Subjects who complete Week 54 or withdrawn will be down titrated over a 1 to 4 weeks period.

ropiniroleIR-PR group

Group Type: ACTIVE_COMPARATOR

ropinirole PR/XR

Intervention Type: DRUG

Double-blind non-inferiority verification phase (24 weeks) At the baseline visit (Week 0), subjects who completed screening period will be randomised (1:1) to double-blind treatment with either ropinirole PR-PR group or ropinirole IR-PR group.

The subjects'dose will be titrated according to the recommended schedule to achieve an optimal therapeutic response (ropinirolePR/XR2-15 mg/day ,ropinirolIR0.75-15 mg/day).

Double-blind PR/XR switching phase (8 weeks) Ropinirole IR-PR subjects will be switched overnight to a similar dose of ropinirole PR/XR, while the remaining ropinirole PR-PR group will continue on the same dosage.

Double blind long-term treatment phase (22 weeks) The same dose level at the end of PR/XR switching phase will be continued till week 54 under blind.

Down titration phase Subjects who complete Week 54 or withdrawn will be down titrated over a 1 to 4 weeks period.

ropinirole IR

Intervention Type: DRUG

Double-blind non-inferiority verification phase (24 weeks) At the baseline visit (Week 0), subjects who completed screening period will be randomised (1:1) to double-blind treatment with either ropinirole PR-PR group or ropinirole IR-PR group.

The subjects'dose will be titrated according to the recommended schedule to achieve an optimal therapeutic response (ropinirolePR/XR2-15 mg/day ,ropinirolIR0.75-15 mg/day).

Double-blind PR/XR switching phase (8 weeks) Ropinirole IR-PR subjects will be switched overnight to a similar dose of ropinirole PR/XR, while the remaining ropinirole PR-PR group will continue on the same dosage.

Double blind long-term treatment phase (22 weeks) The same dose level at the end of PR/XR switching phase will be continued till week 54 under blind.

Down titration phase Subjects who complete Week 54 or withdrawn will be down titrated over a 1 to 4 weeks period.

Interventions

ropinirole PR/XR

Double-blind non-inferiority verification phase (24 weeks) At the baseline visit (Week 0), subjects who completed screening period will be randomised (1:1) to double-blind treatment with either ropinirole PR-PR group or ropinirole IR-PR group.

The subjects'dose will be titrated according to the recommended schedule to achieve an optimal therapeutic response (ropinirolePR/XR2-15 mg/day ,ropinirolIR0.75-15 mg/day).

Double-blind PR/XR switching phase (8 weeks) Ropinirole IR-PR subjects will be switched overnight to a similar dose of ropinirole PR/XR, while the remaining ropinirole PR-PR group will continue on the same dosage.

Double blind long-term treatment phase (22 weeks) The same dose level at the end of PR/XR switching phase will be continued till week 54 under blind.

Down titration phase Subjects who complete Week 54 or withdrawn will be down titrated over a 1 to 4 weeks period.

Intervention Type: DRUG

ropinirole IR

Double-blind non-inferiority verification phase (24 weeks) At the baseline visit (Week 0), subjects who completed screening period will be randomised (1:1) to double-blind treatment with either ropinirole PR-PR group or ropinirole IR-PR group.

The subjects'dose will be titrated according to the recommended schedule to achieve an optimal therapeutic response (ropinirolePR/XR2-15 mg/day ,ropinirolIR0.75-15 mg/day).

Double-blind PR/XR switching phase (8 weeks) Ropinirole IR-PR subjects will be switched overnight to a similar dose of ropinirole PR/XR, while the remaining ropinirole PR-PR group will continue on the same dosage.

Double blind long-term treatment phase (22 weeks) The same dose level at the end of PR/XR switching phase will be continued till week 54 under blind.

Down titration phase Subjects who complete Week 54 or withdrawn will be down titrated over a 1 to 4 weeks period.

Intervention Type: DRUG

Other Intervention Names

ropinirole IR-PR group

Eligibility Criteria

Inclusion Criteria

• Patients who are diagnosed with advanced Parkinson's disease (PD) with severity of the modified Hoehn & Yahr criteria Stages II-IV.
• Subjects receiving a stable dose of L-dopa for at least 4 weeks prior to screening phase and demonstrating lack of control with L-dopa therapy in the following circumstances. Wearing-off phenomena. On-off fluctuations. Delayed-on/No on phenomena. Not adequately controlled on L-dopa
• QTc<450 millisecond (msec) or <480msec for patients with Bundle Branch Block - values based on either single ECG values or triplicate electrocardiogram (ECG) averaged QTc values obtained over a brief recording period.
• Age:20 years or older(at the time of informed written consent)
• Informed consent: Patients who are able to give informed written consent in person. (i.e. patients who are capable of giving informed written consent on one's own)
• Sex: either sex. Female of child-bearing potential will be eligible for inclusion in this study. However they have to have a negative pregnancy test at the screening visit, agree to further pregnancy testing at the time points determined in study assessments and procedures and practice one of the following methods of contraception from the screening visit until the end of the follow-up examination. Abstinence. Injectable progestogen. Implants of levonorgestrel. Estrogenic vaginal ring. Percutaneous contraceptive patches. Intrauterine device (IUD) or intrauterine system (IUS) that meets the SOP effectiveness criteria as stated in the product label. Male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. Double barrier method: condom or occlusive cap (diaphragm or cervical / vault caps) plus spermicidal agent (foam /gel / film / cream / suppository)
• Both inpatient and outpatient status.

-Patients whose Unified Parkinson's Disease Rating Scale (UPDRS) PartIII total (on) scores is 10 points or more at week 0.

Exclusion Criteria

• Late stage advanced subjects demonstrating incapacitating peak dose or biphasic dyskinesia on their stable dose of L-dopa.
• Patients who present serious physical signs and symptoms other than those of the PD (e.g. cardiac/hepatic/renal disorder and haematopoietic disorder). The severity refers to Grade 3 according to "the Classification of the Severity of Adverse Experiences (Pharmaceutical affairs bureau/Safety division (PAB/SD) Notification No. 80, dated 29 June 1992).
• Patients with symptomatic postural hypotension. (e.g. dizziness and syncope).
• Patients with a current or history of drug abuse or alcoholism.
• Patients who have received surgical treatment for PD in the past (e.g. pallidectomy, deep brain stimulation).
• Female patients who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study or within 30 days after the last dose of the study drug.
• Patients with chronic hepatitis typeB and/or type C which is positive of hepatitis B surface antigen (HBsAg) and/or hepatitis C antibody.
• Patients with a history of drug allergy to ropinirole hydrochloride (HCl).
• Patients with a current or history of cancer or malignant tumor.
• Others whom the investigator (subinvestigator) considers ineligible for the study.

• Patients with severe dementia (e.g. score 3 or 4 of the UPDRS item 1 (Intellectual Impairment))
• Patients with current or history of major psychosis (e.g. schizophrenia or psychotic depression) core 3 or 4 of the UPDRS item 2 (thought disorder) or item 3(depression).
• Patients who have used any dopamine agonist within 4 weeks prior to the non-inferiority verification phase
• Patients who have been treated with the following drugs at 4 weeks or earlier before the start of the non-inferiority verification phase, and whose treatment regimen of the drug has been changed. Anticholinergic agents: trihexyphenidyl hydrochloride (e.g. Artane®), piroheptine hydrochloride (Trimol®), mazaticol hydrochloride (Pentona®), metixene hydrochloride (Cholinfall®), biperiden hydrochloride (Akineton®), profenamine (Parkin®), amantadine hydrochloride (e.g. Symmetrel®),droxidopa (Dops®), citicoline (e.g. Nicholin®), selegiline hydrochloride (FP®), entacapone, (comutan®) zonisamide, Estrogens: e.g. estriol (e.g. Estriel®), CYP1A2 inhibitors: Ciprofloxacin HCl (e.g. Ciproxan®, enoxacin and fluvoxamine).
• Patients who have been treated with any other investigational drug within 12 weeks prior to the treatment phase.

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Aichi, , Japan

GSK Investigational Site

Akita, , Japan

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Ehime, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukushima, , Japan

GSK Investigational Site

Hokkaido, , Japan

GSK Investigational Site

Hyōgo, , Japan

GSK Investigational Site

Hyōgo, , Japan

GSK Investigational Site

Hyōgo, , Japan

GSK Investigational Site

Ibaraki, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kanagawa, , Japan

GSK Investigational Site

Kyoto, , Japan

GSK Investigational Site

Kyoto, , Japan

GSK Investigational Site

Kyoto, , Japan

GSK Investigational Site

Kyoto, , Japan

GSK Investigational Site

Miyagi, , Japan

GSK Investigational Site

Nagano, , Japan

GSK Investigational Site

Nagano, , Japan

GSK Investigational Site

Nagasaki, , Japan

GSK Investigational Site

Nara, , Japan

GSK Investigational Site

Okayama, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Osaka, , Japan

GSK Investigational Site

Saitama, , Japan

GSK Investigational Site

Saitama, , Japan

GSK Investigational Site

Shiga, , Japan

GSK Investigational Site

Shizuoka, , Japan

GSK Investigational Site

Shizuoka, , Japan

GSK Investigational Site

Tochigi, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

GSK Investigational Site

Tokyo, , Japan

Countries

Japan

Study Documents

Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Related Links

https://www.clinicalstudydatarequest.com

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Other Identifiers

106066

Identifier Type: -

Identifier Source: org_study_id