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

NCT00823836 | Completed Phase 3 Results

• 1 other identifier: 106066
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 54

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

Keywords

Ropinirole, advanced Parkinson's disease, L-dopa adjunctive therapy

Outcome Measures

Primary Outcomes (1)

• Mean Change From Week 0 (Baseline) in the Japanese Unified Parkinson's Disease Rating Scale (UPDRS) Part III Total Score at the Final Assessment Point (FAP) (up to Week 24) in the Non-Inferiority Verification Phase

  The Japanese UPDRS assesses the status of Parkinson's Disease (PD) patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. Mean change from Week 0 was calculated as the total score at FAP minus the total score at Week 0. Participants who withdrew before Week 2 and who had only one observation for the part III total score were not included in the analysis.

  Week 0 and FAP (up to Week 24)

Secondary Outcomes (61)

• Percentage of Responders on the Japanese UPDRS Part III Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

  FAP (up to Week 24)

• Mean Change From Week 0 in the Japanese UPDRS Part I Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

  Week 0 and FAP (up to Week 24)

• Mean Change From Week 0 in the Japanese UPDRS Part II (at "On") Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

  Week 0 and FAP (up to Week 24)

• Mean Change From Week 0 in the Japanese UPDRS Part II (at "Off") Total Score at Week 24 in the Non-Inferiority Verification Phase

  Week 0 and FAP (up to Week 24)

• Mean Change From Week 0 in the Japanese UPDRS Part IV Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase

  Week 0 and FAP (up to Week 24)

Study Arms (2)

ropinirolePR-PR group

EXPERIMENTAL

Drug: ropinirole PR/XR

ropiniroleIR-PR group

ACTIVE COMPARATOR

Drug: ropinirole PR/XR; Drug: ropinirole IR

Interventions

ropinirole PR/XR 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.

Also known as: ropinirole IR-PR group

ropiniroleIR-PR group; ropinirolePR-PR group

ropinirole IR 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

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (54)

GSK Investigational Site

Aichi, 454-0933, Japan

Location

GSK Investigational Site

Aichi, 460-0008, Japan

Location

GSK Investigational Site

Aichi, 465-8620, Japan

Location

GSK Investigational Site

Aichi, 489-8642, Japan

Location

GSK Investigational Site

Akita, 010-0874, Japan

Location

GSK Investigational Site

Chiba, 260-8712, Japan

Location

GSK Investigational Site

Chiba, 270-1337, Japan

Location

GSK Investigational Site

Chiba, 270-2251, Japan

Location

GSK Investigational Site

Chiba, 279-0021, Japan

Location

GSK Investigational Site

Chiba, 290-0003, Japan

Location

GSK Investigational Site

Ehime, 791-0295, Japan

Location

GSK Investigational Site

Fukuoka, 800-0296, Japan

Location

GSK Investigational Site

Fukuoka, 814-0180, Japan

Location

GSK Investigational Site

Fukuoka, 816-0864, Japan

Location

GSK Investigational Site

Fukuoka, 819-8585, Japan

Location

GSK Investigational Site

Fukushima, 963-8052, Japan

Location

GSK Investigational Site

Hokkaido, 068-0027, Japan

Location

GSK Investigational Site

Hyōgo, 651-2273, Japan

Location

GSK Investigational Site

Hyōgo, 670-0981, Japan

Location

GSK Investigational Site

Hyōgo, 674-0081, Japan

Location

GSK Investigational Site

Ibaraki, 310-0011, Japan

Location

GSK Investigational Site

Kanagawa, 232-0066, Japan

Location

GSK Investigational Site

Kanagawa, 247-8533, Japan

Location

GSK Investigational Site

Kanagawa, 251-0038, Japan

Location

GSK Investigational Site

Kanagawa, 252-0392, Japan

Location

GSK Investigational Site

Kanagawa, 253-8558, Japan

Location

GSK Investigational Site

Kyoto, 600-8811, Japan

Location

GSK Investigational Site

Kyoto, 601-1495, Japan

Location

GSK Investigational Site

Kyoto, 610-0113, Japan

Location

GSK Investigational Site

Kyoto, 616-8255, Japan

Location

GSK Investigational Site

Miyagi, 983-8520, Japan

Location

GSK Investigational Site

Nagano, 399-0157, Japan

Location

GSK Investigational Site

Nagano, 399-8695, Japan

Location

GSK Investigational Site

Nagasaki, 859-3615, Japan

Location

GSK Investigational Site

Nara, 632-8552, Japan

Location

GSK Investigational Site

Okayama, 703-8265, Japan

Location

GSK Investigational Site

Osaka, 530-8480, Japan

Location

GSK Investigational Site

Osaka, 543-8555, Japan

Location

GSK Investigational Site

Osaka, 560-8552, Japan

Location

GSK Investigational Site

Osaka, 570-8507, Japan

Location

GSK Investigational Site

Osaka, 578-8588, Japan

Location

GSK Investigational Site

Osaka, 590-0132, Japan

Location

GSK Investigational Site

Osaka, 596-8522, Japan

Location

GSK Investigational Site

Osaka, 598-0048, Japan

Location

GSK Investigational Site

Saitama, 343-0032, Japan

Location

GSK Investigational Site

Saitama, 359-1141, Japan

Location

GSK Investigational Site

Shiga, 524-0022, Japan

Location

GSK Investigational Site

Shizuoka, 416-0955, Japan

Location

GSK Investigational Site

Shizuoka, 420-8688, Japan

Location

GSK Investigational Site

Tochigi, 329-0498, Japan

Location

GSK Investigational Site

Tokyo, 113-8431, Japan

Location

GSK Investigational Site

Tokyo, 136-0075, Japan

Location

GSK Investigational Site

Tokyo, 183-8524, Japan

Location

GSK Investigational Site

Tokyo, 202-0004, Japan

Location

Related Links

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

MeSH Terms

Conditions

Parkinson Disease

Interventions

ropinirole

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 15, 2009
• First Posted: January 16, 2009
• Study Start: March 1, 2009
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: January 18, 2017
• Results First Posted: October 7, 2011

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

JP (54)