Clinical Evaluation of Ropinirole PR/XR Tablets in Monotherapy for Parkinson's Disease (PD)

Official Title: “Clinical Evaluation of Ropinirole PR/XR Tablets in Monotherapy for Parkinson's Disease - an Open-Label, Uncontrolled Study -”

This study was designed to evaluate the pharmacokinetic profile, safety and efficacy in Parkinson's Disease patients.

Intervention(s) in this Clinical Trial

• Drug: Ropinirole prolonged release/extended release(PR/XR)
  • Subjects will take the investigational drug once daily at the same time each day, it is recommended that this is in the morning for optimal benefit. Investigational drug is taken for 52 weeks, starting on the next day of the Week 0 visit. One tablet of ropinirole PR/XR 2 mg tablets will be orally dosed as the initial dose. The dose will be titrated weekly by 2 mg/day, and increased to 8 mg/day in Week 4. From Week 5 up to 16, the dose will be increased at minimum intervals of one week between titration steps until sufficient efficacy is obtained, according to individual clinical response and tolerability (the dose may be titrated up to 16 mg/day). In Week 16 and further, treatment dose at Week 16 will be continuously administered up to Week 52. If insufficient efficacy is judged in a subject during treatment, or unable to maintain the dose due to adverse event, the treatment dose may be changed. The dose is down tapered according to the maintenance dose at Week 52 (or withdrawal).

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Ropinirole PR/XR

Primary Measures

• Food Effects on Cmax and Cmin of SKF101468 (Ropinirole) and Its Metabolites
  • Time Frame: Weeks 5-16
    Safety Issue?: No
• Food Effects on AUC0-24 of SKF101468 (Ropinirole) and Its Metabolites
  • Time Frame: Weeks 5-16
    Safety Issue?: No
• Food Effects on Tmax of SKF101468 (Ropinirole) and Its Metabolites
  • Time Frame: Weeks 5-16
    Safety Issue?: No
• Plasma Trough Concentrations of SKF101468 (Ropinirole) and Its Metabolites
  • Time Frame: Weeks 1-16
    Safety Issue?: No

Secondary Measures

• Total Score in the Japanese UPDRS Part III
  • Time Frame: Weeks 0-52
    Safety Issue?: No
• Change From Baseline in the Japanese UPDRS Part III
  • Time Frame: Baseline (Week 0) and Weeks 1-52
    Safety Issue?: No
• Percent Change From Baseline in the Japanese UPDRS Part III
  • Time Frame: Baseline (Week 0) and Weeks 1-52
    Safety Issue?: No
• Percentage of Responders of the Total Score in the Japanese UPDRS Total Score in Part III
  • Time Frame: Baseline (Week 0) and Weeks 1-52
    Safety Issue?: No
• Total Score in the Japanese UPDRS Part I
  • Time Frame: Weeks 0-52
    Safety Issue?: No
• Change From Baseline in the Japanese UPDRS Part I
  • Time Frame: Baseline (Week 0) and Weeks 1-52
    Safety Issue?: No
• Percent Change From Baseline in the Japanese UPDRS Part I
  • Time Frame: Baseline (Week 0) and Weeks 1-52
    Safety Issue?: No
• Total Score in the Japanese UPDRS Part II
  • Time Frame: Weeks 0-52
    Safety Issue?: No
• Change From Baseline in the Japanese UPDRS Part II
  • Time Frame: Baseline (Week 0) and Weeks 1-52
    Safety Issue?: No
• Percent Change From Baseline in the Japanese UPDRS Part II
  • Time Frame: Baseline (Week 0) and Weeks 1-52
    Safety Issue?: No
• Total Score in the Japanese UPDRS Part IV
  • Time Frame: Baseline (Week 0) and Weeks 0-52
    Safety Issue?: No
• Change From Baseline in the Japanese UPDRS Part IV
  • Time Frame: Baseline (Week 0) and Weeks 1-52
    Safety Issue?: No
• Percent Change From Baseline in the Japanese UPDRS Part IV
  • Time Frame: Baseline (Week 0) and Weeks 1-52
    Safety Issue?: No
• Summary of the Modified Hoehn & Yahr Criteria Stages
  • Time Frame: Screening-Week 52
    Safety Issue?: No
• Number of Participants Scored as Responders on the Clinician's Global Impression (CGI) Scale
  • Time Frame: Weeks 1-52
    Safety Issue?: No
• Percentage of Participants Who Remained in the Study on the Indicated Days
  • Time Frame: Days 0-364
    Safety Issue?: No
• Change From Baseline in Albumin, Total Protein, and Hemoglobin at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No
• Change From Baseline in Alkaline Phosphatase, Alanine Amino Transferase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase, and Lactate Dehydrogenase at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No
• Change From Baseline in Total Bilirubin, Blood Urea Nitrogen, and Creatinine at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No
• Change From Baseline in Blood Urea Nitrogen, Cholesterol, Chloride, Potassium, and Sodium at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No
• Change From Baseline in Prolactin at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No
• Change From Baseline in Hematocrit at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No
• Change From Baseline in Platelet Count and White Blood Cell Count at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No
• Change From Baseline in Red Blood Cell Count at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No
• Urinalysis Data
  • Time Frame: Screening, Week 16, and Week 52
    Safety Issue?: No
• Number of Participants With the Indicated Shift From Baseline in 12-Lead Electrocardiogram (ECG) Findings at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No
• Change From Baseline in Supine and Standing Systolic and Diastolic Blood Pressure at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No
• Change From Baseline in Supine and Standing Pulse Rate at Weeks 16 and 52
  • Time Frame: Baseline (Screening) and Weeks 16 and 52
    Safety Issue?: No

Inclusion Criteria:

• Patients who are diagnosed with PD with severity of the Modified Hoehn & Yahr staging at Stage I to III.
• Age: 20 years or older (at the time of giving informed consent)
• Gender: male and female
• Both inpatient and outpatient status
• 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)
• Limited prior exposure to low or moderate doses of L-dopa (up to 3 months in total) or dopamine agonists (up to 6 months in total) provided treatment is discontinued for a minimum of 4 weeks prior to screening.

Exclusion Criteria:

• Patients who present serious physical signs and symptoms other than those of the PD (e.g. cardiac/hepatic/renal disorder and haematopoietic disorder). The seriousness 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 who have had serious psychiatric symptoms (e.g. confusion, hallucination, delusion, abnormal behaviour, alcohol or drug dependence) during the past six months (26 weeks) (including symptoms caused by anti-Parkinson drugs).
• Patients who have been treated with the following drugs at Week -4, and whose treatment regimen of the drug has been changed from Week -4 to Week 0.
• 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®)
• zonisamide
• estrogen: estriol (e.g.Estriel®)
• CYP1A2 inhibitors: Ciprofloxacin HCl (e.g. Ciproxan®, enoxacin and fluvoxamine)
• Patients with severe dementia such as score 3 or 4 of the UPDRS Part I (Mentation, behaviour, and mood)
• 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 current history or complication of carcinoma or malignant tumour.
• Patients who have history of drug allergy to ropinirole hydrochloride (HCl).
• Patients who have received surgical treatment for PD in the past (e.g. pallidectomy, deep brain stimulation).
• Patients who have been treated with any other investigational drug within 12weeks prior to the treatment phase.
• Others whom the investigator (sub investigator) considers ineligible for the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: GlaxoSmithKline Industry

Overall Clinical Trial Officials and Contacts

GSK Clinical Trials Study Director GlaxoSmithKline  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00434304

Study ID Number: ROP106064

ClinicalTrials.gov Identifier: NCT00434304

Health Authority: Japan: Ministry of Health, Labor and Welfare