Clinical trial NCT00823836: Clinical Evaluation of Ropinirole Prolonged Release/Extended Release (PR/XR) Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease
Official title: Clinical Evaluation of Ropinirole PR/XR Tablet for Adjunctive Therapy to L-dopa in Subjects With Advanced Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson Disease
Keywords: Ropinirole, advanced Parkinson's disease, L-dopa adjunctive therapy
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2009-01-16
Enrollment: 302
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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
timeFrame: Week 0 and FAP (up to Week 24)
Secondary outcomes:
measure: Percentage of Responders on the Japanese UPDRS Part III Total Score at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: FAP (up to Week 24)
measure: 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
timeFrame: Week 0 and FAP (up to Week 24)
measure: 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
timeFrame: Week 0 and FAP (up to Week 24)
measure: Mean Change From Week 0 in the Japanese UPDRS Part II (at "Off") Total Score at Week 24 in the Non-Inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: 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
timeFrame: Week 0 and FAP (up to Week 24)
measure: Japanese UPDRS Part I Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Japanese UPDRS Part II (at "On") Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Japanese UPDRS Part II (at "Off") Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Japanese UPDRS Part III Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Japanese UPDRS Part IV Total Score at Week 0 and FAP (up to Week 24) in the Non-inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Percentage of Responders on the Clinical Global Impression-Improvement (CGI-I) at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: FAP (up to Week 24)
measure: Percentage of Responders in Change From Week 0 in Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: FAP (up to Week 24)
measure: Percentage of Responders in Percent Change From Week 0 in Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: FAP (up to Week 24)
measure: Mean Change From Week 0 in Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Mean Change From Week 0 in Percentage of Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Mean Percent Change From Week 0 in Percentage of Awake Time Spent "Off" at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Mean Change From Week 0 in Awake Time Spent "On" at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Mean Change From Week 0 in Percentage of Awake Time Spent "On" at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Mean Change From Week 0 in Awake Time Spent "On" With Troublesome Dyskinesias at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Mean Change From Week 0 in Percentage of Awake Time Spent "On" With Troublesome Dyskinesias at FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "On") at Week 0 and FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "Off") at Week 0 and FAP (up to Week 24) in the Non-Inferiority Verification Phase
timeFrame: Week 0 and FAP (up to Week 24)
measure: Percentage of Participants Remaining in the Study on the Indicated Days During the Non-Inferiority Verification Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: 0-175 days (up to Week 24)
measure: Percentage of Participants Remaining in the Study on the Indicated Days During the Non-Inferiority Verification Phase in the Ropinirole IR-Ropinirole PR Group
timeFrame: 0-175 days (up to Week 24)
measure: Mean Change From Week 24 (Period Baseline) in the Japanese UPDRS Part I Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Mean Change From Week 24 in the Japanese UPDRS Part II (at "On") Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Mean Change From Week 24 in the Japanese UPDRS Part II (at "Off") Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Mean Change From Week 24 in the Japanese UPDRS Part III Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Mean Change From Week 24 in the Japanese UPDRS Part IV Total Score at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Japanese UPDRS Part I Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Japanese UPDRS Part II (at "On") Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Japanese UPDRS Part II (at "Off") Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Japanese UPDRS Part III Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Japanese UPDRS Part IV Total Score at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Mean Change From Week 24 in Awake Time Spent "Off" at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Mean Change From Week 24 in Percentage of Awake Time Spent "Off" at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Mean Change From Week 24 in Awake Time Spent "On" With Troublesome Dyskinesias at FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "On") at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "Off") at Week 24 and FAP (From Week 26 up to Week 32) in the PR/XR Switching Phase
timeFrame: Week 24 and FAP (from Week 26 up to Week 32)
measure: Percentage of Participants Remaining in the Study on the Indicated Days During the PR/XR Switching Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: 0-89 days within the PR/XR Switching Phase (between Weeks 24 and 32)
measure: Percentage of Participants Remaining in the Study on the Indicated Days During the PR/XR Switching Phase in the Ropinirole IR-Ropinirole PR Group
timeFrame: 0-89 days within the PR/XR Switching Phase (between Weeks 24 and 32)
measure: Percentage of Responders on the Japanese UPDRS Part III Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Week 54
measure: Mean Change From Week 0 in the Japanese UPDRS Part I Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Mean Change From Week 0 in the Japanese UPDRS Part II (at "On") Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Mean Change From Week 0 in the Japanese UPDRS Part II (at "Off") Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Mean Change From Week 0 in the Japanese UPDRS Part III Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Mean Change From Week 0 in the Japanese UPDRS Part IV Total Score at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Japanese UPDRS Part I Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Japanese UPDRS Part II (at "On") Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Japanese UPDRS Part II (at "Off") Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Japanese UPDRS Part III Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Japanese UPDRS Part IV Total Score at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Percentage of Responders on the CGI-I at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Week 54
measure: Percentage of Responders in Change From Week 0 in Awake Time Spent "Off" at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Week 54
measure: Percentage of Responders in Percent Change From Week 0 in Awake Time Spent "Off" at Week 54 in the Long-term Phase
timeFrame: Week 54
measure: Mean Change From Week 0 in Awake Time Spent "Off" at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Mean Change From Week 0 in Percentage of Awake Time Spent "Off" at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Mean Change From Week 0 in Awake Time Spent "On" With Troublesome Dyskinesias at Week 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "On") at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Number of Participants at Each Stage of the Modified Hoehn & Yahr Severity of Illness (at "Off") at Weeks 0 and 54 in the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: Weeks 0 and 54
measure: Percentage of Participants Remaining in the Study on the Indicated Days During the Long-term Phase in the Ropinirole PR-Ropinirole PR Group
timeFrame: 0-385 days (up to Week 54)
Other outcomes:
Locations:
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Aichi
country: Japan
facility: GSK Investigational Site
city: Akita
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Ehime
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukushima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kyoto
country: Japan
facility: GSK Investigational Site
city: Kyoto
country: Japan
facility: GSK Investigational Site
city: Kyoto
country: Japan
facility: GSK Investigational Site
city: Kyoto
country: Japan
facility: GSK Investigational Site
city: Miyagi
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Nara
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Saitama
country: Japan
facility: GSK Investigational Site
city: Shiga
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Shizuoka
country: Japan
facility: GSK Investigational Site
city: Tochigi
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: