Clinical Evaluation of Ropinirole PR/XR Tablets in Monotherapy for Parkinson's Disease - an Open-Label, Uncontrolled Study -
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 62
- Locations
- 1
- Primary Endpoint
- Food Effects on AUC0-24 of SKF101468 (Ropinirole) and Its Metabolites
Study Overview
Brief Summary
This study was designed to evaluate the pharmacokinetic profile, safety and efficacy in Parkinson's Disease patients.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 20 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- 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
- •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.
Arms & Interventions
Ropinirole PR/XR
Intervention: Ropinirole prolonged release/extended release(PR/XR) (Drug)
Outcomes
Primary Outcomes
Food Effects on AUC0-24 of SKF101468 (Ropinirole) and Its Metabolites
Time Frame: Weeks 5-16
The dose of SKF101468 and its metabolites was normalized to 1 mg. Blood sampling at steady state up to 24 hours (hr) post dose after receiving the maintenance dose was conducted. In order to investigate the effect of a meal on pharmacokinetics, blood was sampled twice (after a standard morning meal and at fasted state) from identical participants. AUC0-24: area under the drug concentration 24 hr curve.
Food Effects on Tmax of SKF101468 (Ropinirole) and Its Metabolites
Time Frame: Weeks 5-16
The dose of SKF101468 and its metabolites was normalized to 1 mg. Blood sampling at steady state up to 24 hours post dose after receiving the maintenance dose was conducted. In order to investigate the effect of a meal on pharmacokinetics, blood was sampled twice (after a standard morning meal and at fasted state) from identical participants. Tmax: time of maximum concentration. Data are presented as the median difference between fed and fasted states for ropinirole and each metabolite.
Food Effects on Cmax and Cmin of SKF101468 (Ropinirole) and Its Metabolites
Time Frame: Weeks 5-16
The dose of SKF101468 and its metabolites was normalized to 1 mg. Blood sampling at steady state up to 24 hours post dose after receiving the maintenance dose was conducted. In order to investigate the effect of a meal on pharmacokinetics, blood was sampled twice (after a standard morning meal and at fasted state) from identical participants. Cmax: maximum concentration, Cmin: trough plasma concentration.
Plasma Trough Concentrations of SKF101468 (Ropinirole) and Its Metabolites
Time Frame: Weeks 1-16
Blood sampling in the fixed titration phase will be performed at 24 hour post dose of the last dose of 2, 4, and 8 mg (immediately before the morning dose). Blood sampling in the maintenance dose phase will be performed at 24 hour post dose of 10 mg or more for one week or longer (immediately before the morning dose), as sampling needs to be conducted at steady state.
Secondary Outcomes
- Total Score in the Japanese UPDRS Part I(Weeks 0-52)
- Percentage of Participants Who Remained in the Study on the Indicated Days(Days 0-364)
- Percent Change From Baseline in the Japanese UPDRS Part I(Baseline (Week 0) and Weeks 1-52)
- Total Score in the Japanese UPDRS Part II(Weeks 0-52)
- Percent Change From Baseline in the Japanese UPDRS Part II(Baseline (Week 0) and Weeks 1-52)
- Change From Baseline in Supine and Standing Systolic and Diastolic Blood Pressure at Weeks 16 and 52(Baseline (Screening) and Weeks 16 and 52)
- Percent Change From Baseline in the Japanese UPDRS Part III(Baseline (Week 0) and Weeks 1-52)
- Change From Baseline in Total Bilirubin, Blood Urea Nitrogen, and Creatinine at Weeks 16 and 52(Baseline (Screening) and Weeks 16 and 52)
- Change From Baseline in Prolactin at Weeks 16 and 52(Baseline (Screening) and Weeks 16 and 52)
- Total Score in the Japanese UPDRS Part III(Weeks 0-52)
- Change From Baseline in the Japanese UPDRS Part III(Baseline (Week 0) and Weeks 1-52)
- Change From Baseline in the Japanese UPDRS Part I(Baseline (Week 0) and Weeks 1-52)
- Change From Baseline in the Japanese UPDRS Part II(Baseline (Week 0) and Weeks 1-52)
- Total Score in the Japanese UPDRS Part IV(Baseline (Week 0) and Weeks 0-52)
- Number of Participants Scored as Responders on the Clinician's Global Impression (CGI) Scale(Weeks 1-52)
- Percentage of Responders of the Total Score in the Japanese UPDRS Total Score in Part III(Baseline (Week 0) and Weeks 1-52)
- Change From Baseline in the Japanese UPDRS Part IV(Baseline (Week 0) and Weeks 1-52)
- Summary of the Modified Hoehn & Yahr Criteria Stages(Screening-Week 52)
- Urinalysis Data(Screening, Week 16, and Week 52)
- Percent Change From Baseline in the Japanese UPDRS Part IV(Baseline (Week 0) and Weeks 1-52)
- Change From Baseline in Albumin, Total Protein, and Hemoglobin at Weeks 16 and 52(Baseline (Screening) and Weeks 16 and 52)
- Change From Baseline in Blood Urea Nitrogen, Cholesterol, Chloride, Potassium, and Sodium at Weeks 16 and 52(Baseline (Screening) and Weeks 16 and 52)
- Change From Baseline in Platelet Count and White Blood Cell Count at Weeks 16 and 52(Baseline (Screening) and Weeks 16 and 52)
- 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(Baseline (Screening) and Weeks 16 and 52)
- Change From Baseline in Hematocrit at Weeks 16 and 52(Baseline (Screening) and Weeks 16 and 52)
- Change From Baseline in Red Blood Cell Count at Weeks 16 and 52(Baseline (Screening) and Weeks 16 and 52)
- Number of Participants With the Indicated Shift From Baseline in 12-Lead Electrocardiogram (ECG) Findings at Weeks 16 and 52(Baseline (Screening) and Weeks 16 and 52)
- Change From Baseline in Supine and Standing Pulse Rate at Weeks 16 and 52(Baseline (Screening) and Weeks 16 and 52)