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

• Status: Completed
• Trial end date: 2010-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Levodopa; Ropinirole

Criteria

Inclusion Criteria:

Inclusion criteria at the start of the screening

• 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.

Inclusion Criteria at the start of the non-inferiority verification phase

-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.

Exclusion criteria at the start of the non-inferiority verification phase

• 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.