A Study to Evaluate the Efficacy of 18 to 24mg/Day Ropinirole Controlled Release (CR) Tablets in Early and Advanced Parkinson's Disease (PD) Patients.

NCT01929317 | Terminated Phase 3 Results

• 1 other identifier: 116991
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 17

Brief Summary

This study is a Phase III, multicentre, randomized, initial double-blind study with subsequent open label phases. The study will havea screening phase (4 weeks), a dose increase effect verification phase (12 weeks), a down titration 1 phase (1 week), a long-term phase (39 weeks), down titration 2 phase (1 to 2 weeks) and a follow up phase. Subjects will be assigned to Ropinirole CR high-dose group or Ropinirole CR maintenance group at a ratio of 3:1. This study is being conducted to evaluate the efficacy (effect of increasing Ropinirole dose from 16 mg/day to 18-24 mg/day) of the Ropinirole CR tablets in early and advanced PD patients who have not achieved an optimal therapeutic response with marketed Ropinirole Immediate release (IR) (15 mg/day) or marketed Ropinirole CR (16 mg/day) formulations.

Conditions

Parkinson Disease

Keywords

Ropinirole; Parkinson's disease

Outcome Measures

Primary Outcomes (1)

• Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at Week 12 in the CR High-dose Group

  The Japanese Unified Parkinson's Disease Rating Scale (UPDRS) assesses the status of Parkinson's Disease (PD) participants objectively. Part III assessed motor examination on 27 items. Participants received a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. Baseline is defined as the value evaluated at Week 0. Mean change from Baseline was calculated as the total score at Week 12 minus the total score at Baseline. The analyses for the Dose Increase Effect Verification Phase was performed using the last observation carried forward (LOCF) data. In the LOCF data, the last available data was used for the imputation for missing data at a planned visit. The imputation was conducted using the data within only the Dose Increase Effect Verification Phase; therefore, the value observed in the Dose Increase Effect Verification Phase was not used to impute a missing data in the Long-term Phase.

  Baseline and Week 12

Secondary Outcomes (30)

• Mean Change From Baseline (Week 0) in UPDRS Part III Total Score at the Indicated Visits

  Baseline, Weeks, 2, 4, 6, 8 and 12

• Number of Participants Achieving a 30% and 20% Reduction From Baseline in the UPDRS Total Part 3 Score at the Indicated Visits in the Dose Increase Effect Verification Phase

  Baseline, Weeks, 2, 4, 6, 8 and 12

• Change From Baseline in the Japanese UPDRS Part 1 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

  Baseline, Weeks, 2, 4, 6, 8 and 12

• Change From Baseline in the Japanese UPDRS Part 2 Total Score at the Indicated Visits by the on/Off Status in the Dose Increase Effect Verification Phase

  Baseline, Weeks, 2, 4, 6, 8 and 12

• Change From Baseline in the Japanese UPDRS Part 4 Total Score at the Indicated Visits in the Dose Increase Effect Verification Phase

  Baseline, Weeks, 2, 4, 6, 8 and 12

Study Arms (2)

Ropinirole CR high-dose group

EXPERIMENTAL

The subjects will receive Ropinirole CR 16mg/day for 4 weeks in screening phase. After randomization the subject will enter dose increase effect verification phase, where Ropinirole CR dose will titrated (2 mg /day/week) from 18 mg/day up to a maximum 24mg/day at intervals of 1 week or longer for 8 weeks, till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose for 4 weeks. This will be followed by a down titration phase of one week and long term phase of 39 weeks in which the subjects will receive incremental doses (2 mg /day/week) of Ropinirole CR from 18 mg/day till to a maximum of 24 mg/day till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose. Subjects completing the long term phase will undergo a down titration phase of 1 to 2 weeks.

Drug: Ropinirole CR 2mg tablet; Drug: Ropinirole CR 8mg tablet

Ropinirole CR maintenance group

EXPERIMENTAL

The subjects will receive Ropinirole CR 16mg/day for 4 weeks in screening phase. After randomization the subject will enter dose increase effect verification phase and Ropinirole CR dose will maintained at 16mg/day and placebo will be increased at intervals of 1 week for 8 weeks till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose for 4 weeks. This will be followed by a down titration phase of one week and long term phase of 39 weeks in which the subjects will receive incremental doses (2 mg/day/week) of Ropinirole CR from 18 mg/day till to a maximum of 24 mg/day till subject reaches a dose level above which further symptomatic improvement cannot be expected; the subject will be maintained on that dose. Subjects completing the long term phase will undergo a down titration phase of 1 to 2 weeks.

Drug: Ropinirole CR 2mg tablet; Drug: Ropinirole CR 8mg tablet; Drug: Ropinirole CR matching Placebo tablet

Interventions

Ropinirole CR 2mg tablet DRUG

Ropinirole CR 2mg tablets will be supplied as white oval film-coated tablets.

Ropinirole CR high-dose group; Ropinirole CR maintenance group

Ropinirole CR 8mg tablet DRUG

Ropinirole CR 8mg tablets will be supplied as white oval film-coated tablets.

Ropinirole CR high-dose group; Ropinirole CR maintenance group

Ropinirole CR matching Placebo tablet DRUG

Ropinirole CR matching Placebo tablet tablets (containing no active ingredients) indistinguishable in appearance from Ropinirole CR 2 mg tablets.

Ropinirole CR maintenance 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 as Parkinson's Disease with severity of the modified Hoehn \& Yahr criteria Stages I-IV.
• \) Monotherapy subject: Subjects who have never received L-dopa, or subjects who have had prior exposure to L-dopa (up to 450 milligram (mg)/day) for up to 3 months in total and L-dopa treatment has been discontinued, for a minimum of 4 weeks prior to the screening phase. 2) L-dopa adjunct subject: Subjects receiving L-dopa (up to 450 mg/day) for at least 4 weeks prior to the screening phase.
• Patients receiving 15mg/day Ropinirole IR or 16mg/day Ropinirole CR for 4 weeks prior to the screening phase, UPDRS Part III total (on) scores is 10 points or more at screening visit and can expect clinical efficacy by increasing Ropinirole CR.
• Age: 20years 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 their own)
• corrected QT (QTc) \<450 millisecond (msec) or \<480msec for subjects with Bundle Branch Block. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
• Liver function tests: Patients with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2x upper limit of normal (ULN); and Alkaline Phosphatase and bilirubin =\< 1.5xULN (isolated bilirubin \> 1.5ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%) at the screening visit.
• Randomization Criteria
• Patients whose UPDRS Part III total (on) scores is 10 points or more at week 0
• Patients who did not achieve an optimal therapeutic response by treatment with 16mg/day Ropinirole CR and required higher dose of Ropinirole CR
• Patients who are 80% or more compliant taking study drug

You may not qualify if:

• Late stage advanced patients demonstrating incapacitating peak dose or biphasic dyskinsia on their stable dose of L-dopa.
• Patients who have used any other dopamine agonist (except for Ropinirole IR and CR) within 4 weeks prior to the screening phase.
• Patients who have been treated with the following drugs at 4 weeks or earlier before the start of the screening phase, and whose treatment regimen of the drug has been changed. Anticholinergic agents: trihexyphenidyl hydrochloride, piroheptine hydrochloride, mazaticol hydrochloride, metixene hydrochloride, biperiden hydrochloride, profenamine, amantadine hydrochloride,droxidopa, citicoline, selegiline hydrochloride, entacapone, zonisamide, Estrogens, CYP1A2 inhibitors.
• Patients who have been changing in smoking habit (started or stopped smoking) within the screening phase.
• Patients who have been treated with any other investigational drug within 12 weeks prior to the screening phase.
• Patients who present serious physical signs and symptoms other than those of the PD (e.g. cardiac/hepatic/renal disorder and haematopoietic disorder).
• Patients with symptomatic postural hypotension. (e.g. dizziness and syncope).
• Patients with a current or history of drug abuse or alcoholism.
• Patients with severe dementia such as score 3 or 4 of the UPDRS item 1 (Mentation, behaviour, and mood).
• Patients with current or history of major psychosis (e.g. schizophrenia or psychotic depression) such as score 3 or 4 of the UPDRS item 2 (thought disorder) or item 3(depression).
• 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.
• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulapathy, hypoalbuminaemia, oesophageal or gastric varices or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). Chronic hepatitis B administered immunosuppressive agents due to risk of hapatitis B reactivation.
• Patients with a history of drug allergy to Ropinirole hydrochloride.
• Except for patients with a history of basal cell carcinoma, patients with a current or history of cancer or malignant tumor within 5 years prior to the screening phase.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (17)

GSK Investigational Site

Aichi, 466-8560, Japan

Location

GSK Investigational Site

Akita, 010-0874, Japan

Location

GSK Investigational Site

Aomori, 030-8553, Japan

Location

GSK Investigational Site

Hokkaido, 070-8530, Japan

Location

GSK Investigational Site

Hokkaido, 070-8644, Japan

Location

GSK Investigational Site

Hyōgo, 672-8043, Japan

Location

GSK Investigational Site

Hyōgo, 674-0081, Japan

Location

GSK Investigational Site

Kagawa, 760-0027, Japan

Location

GSK Investigational Site

Kanagawa, 252-0392, Japan

Location

GSK Investigational Site

Kyoto, 600-8811, Japan

Location

GSK Investigational Site

Numakunai, 020-0878, Japan

Location

GSK Investigational Site

Numakunai, 025-0075, Japan

Location

GSK Investigational Site

Okayama, 703-8265, Japan

Location

GSK Investigational Site

Osaka, 530-8480, Japan

Location

GSK Investigational Site

Osaka, 578-8588, Japan

Location

GSK Investigational Site

Shizuoka, 416-0955, Japan

Location

GSK Investigational Site

Shizuoka, 433-8125, Japan

Location

Related Publications (1)

• Hattori N, Hasegawa K, Sato K, Mitsuyama E, Numachi Y. Clinical evaluation of ropinirole controlled-release formulation at 18-24 mg/day in Japanese patients with Parkinson's disease. Parkinsonism Relat Disord. 2017 Jul;40:33-39. doi: 10.1016/j.parkreldis.2017.04.005. Epub 2017 Apr 13.

  PMID: 28442303 DERIVED

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

Tablets

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

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: August 22, 2013
• First Posted: August 27, 2013
• Study Start: August 28, 2013
• Primary Completion: September 16, 2014
• Study Completion: June 9, 2015
• Last Updated: June 20, 2018
• Results First Posted: May 21, 2015

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will share

Locations

JP (17)