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Ropinirole Hydrochloride (ROP) was granted approval for the treatment of Parkinson's Disease (PD) on 20 October 2006.
ROP is expected to be used for a long term in clinical practice. However, no long-term clinical data with ROP administered three times daily are currently available from Japanese patients, and the clinical experience with ROP at >10mg/day is limited.
For this reason, this study was designed as a multicenter open-label uncontrolled study.
This study will evaluate the long-term efficacy (Japanese Unified Parkinson's Disease Rating Scale (UPDRS), Awake time spent "Off"/"On", Modified Hoehn & Yahr stage, Schwab-England scale, Proportion of subjects remaining in this study and Clinical Global Impression (CGI)) and the long-term safety of ROP administered three times daily for in PD patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ropinirole Hydrochloride | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ROP | Drug | Ropinirole Hydrochloride monotherapy group (ROP): Patients will receive ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose will start at 0.75 mg/day and will be increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose will be increased by 1.5 mg/day at intervals of at least 1 week up to a maximum of 15.0 mg/day. The dose will be maintained at a level without further symptomatic improvement is expected. Concomitant use of L-dopa is prohibited during the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in the Japanese Unified Parkinson's Disease Rating Scale (UPDRS) Part III Total Score (in "On" State for the ROP+L-Dopa Group) at Week 52 and Final Assessment Point (FAP) | The Japanese UPDRS assesses the status of Parkinson's Disease (PD) patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. Participants with "off" state at baseline or without post-baseline data were not included in the ROP+L-dopa group at FAP. These participants as well as one with "off" state at Week 52 and those prematurely withdrawn were not included at Week 52. | Baseline, Week 52, and FAP (up to Week 52) |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline in the Japanese UPDRS Part I Total Score at Week 52 and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms. | Baseline, Week 52, and FAP (up to Week 52) |
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Inclusion criteria:
Subjects eligible for enrollment in the study must meet all of the following criteria. Note that both inpatients and outpatients are eligible.
Females of childbearing potential are eligible for enrollment in the study, only if the subject has a negative pregnancy test at the start of the screening phase and agrees to conduct pregnancy testing at the protocol-specified visits during the study and use one of the following acceptable methods of contraceptions properly and accurately:
Exclusion criteria:
Subjects meeting any of the following criteria must not be enrolled in the study:
Serious is defined as Grade 3 as a rule according to the Classification of the Severity of Adverse Experiences.
Patients with postural hypotension with any subjective symptoms (e.g., dizziness and syncope).
Patients who have had any serious psychiatric symptoms (e.g., confusion, hallucination, delusion, abnormal behavior) (including symptoms caused by anti-PD drugs) within 6 months (26 weeks) prior to written informed consent.
Patients who have initiated any of the following drugs within 4 weeks of the start of the screening phase and have the dosing regimen of the drug changed within 4 weeks of the start of the screening phase.
Patients with severe dementia with a Japanese UPDRS Part I (mentation, behavior, and mood) score of 3 or 4.
Female patients who are pregnant or lactating, who may be pregnant, or who plan for pregnancy during the study period or within 30 days after the last dose of the study drug.
Patients with a history of drug allergy to any ingredients of ROP tablets.
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 product within 12 weeks prior to the start of the screening phase.
Patients who, in the judgement of the investigator (or sub-investigator), have evidence of alcohol or drug abuse.
Others whom the investigator (or sub-investigator) considers ineligible for the study.
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| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Chiba | 270-2251 | Japan | |||
| GSK Investigational Site |
52 weeks of Treatment Phase, consisting of 4 weeks of Fixed Titration Phase and 48 weeks of Flexible Titration and Maintenance Phase, was started after 1 to 4 weeks of Screening Phase. Although the results are presented by participants with and without L-dopa, this study was a single-arm design, and L-dopa was not the investigational product.
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| ID | Title | Description |
|---|---|---|
| FG000 | ROP+L-Dopa | Participants received ropinirole hydrochloride (ROP) tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 milligrams (mg)/day and was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals of at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study. |
| FG001 | Ropinirole Hydrochloride | Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day and was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals of at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | ROP+L-Dopa | Participants received ropinirole hydrochloride (ROP) tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 milligrams (mg)/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Mean Change From Baseline in the Japanese Unified Parkinson's Disease Rating Scale (UPDRS) Part III Total Score (in "On" State for the ROP+L-Dopa Group) at Week 52 and Final Assessment Point (FAP) | The Japanese UPDRS assesses the status of Parkinson's Disease (PD) patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. Participants with "off" state at baseline or without post-baseline data were not included in the ROP+L-dopa group at FAP. These participants as well as one with "off" state at Week 52 and those prematurely withdrawn were not included at Week 52. | Full Analysis Set (FAS): all participants enrolled in the Treatment Phase, excluding those with objective measurements not meeting the major eligibility criteria, who did not receive ROP at all, and those with no valid post-baseline data. Last observation carried forward (LOCF) was used for the FAP data to impute post-baseline missing values. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 52, and FAP (up to Week 52) |
From Baseline (Week 0) through the end of follow-up (up to Week 56).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ROP+L-Dopa | Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Meniscus lesion | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 |
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| ID | Term |
|---|---|
| D010300 | Parkinson Disease |
| ID | Term |
|---|---|
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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|
| ROP+L-Dopa | Drug | Ropinirole Hydrochloride with L-Dopa adjunct therapy group (ROP+L-Dopa): Patients will receive ropinirole hydrochloride (ROP) tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose will start at 0.75 milligrams (mg)/day and will be increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose will be increased by 1.5 mg/day at intervals of at least 1 week up to a maximum of 15.0 mg/day. The dose will be maintained at a level without further symptomatic improvement is expected. The dosing regimen of L-dopa remain unchanged from 4 weeks prior to the start of the Screening Phase throughout the study. |
|
| Mean Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. "Off" state is where PD symptoms are not adequately controlled by the drug. | Baseline, Week 52, and FAP (up to Week 52) |
| Mean Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP in the ROP Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. | Baseline, Week 52, and FAP (up to Week 52) |
| Mean Change From Baseline in the Japanese UPDRS Part IV Total Score at Week 52 and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. | Baseline, Week 52, and FAP (up to Week 52) |
| Japanese UPDRS Part I Mean Total Score at Baseline, Week 52, and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms. | Baseline, Week 52, and FAP (up to Week 52) |
| Mean Percent Change From Baseline in the Japanese UPDRS Part I Total Score at Week 52 and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms. Percent change from baseline was calculated as (change from baseline score/baseline score) * 100; change from baseline was calculated as thescore at the observation day minus the baseline score. | Baseline, Week 52, and FAP (up to Week 52) |
| Japanese UPDRS Part II Mean Total Score at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. "Off" state is where PD symptoms are not adequately controlled by the drug. LOCF was used for the FAP data. Some participants were not included at FAP as having no post-baseline data in "on" state or having no data in "off" state at Week 52/withdrawal. | Baseline, Week 52, and FAP (up to Week 52) |
| Japanese UPDRS Part II Mean Total Score at Baseline, Week 52, and FAP in ROP Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. | Baseline, Week 52, and FAP (up to Week 52) |
| Mean Percent Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. "Off" state is where PD symptoms are not adequately controlled by the drug. Percent change from baseline was calculated as (change from baseline score/baseline score) * 100; change from baseline was calculated as thescore at the observation day minus the baseline score. | Baseline, Week 52, and FAP (up to Week 52) |
| Mean Percent Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP in the ROP Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. Percent change from baseline was calculated as (change from baseline score/baseline score) * 100; change from baseline was calculated as thescore at the observation day minus the baseline score. | Baseline, Week 52, and FAP (up to Week 52) |
| Japanese UPDRS Part III Mean Total Score (in "On" State for the ROP+L-Dopa Group) at Baseline, Week 52, and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. | Baseline, Week 52, and FAP (up to Week 52) |
| Mean Percent Change From Baseline in the Japanese UPDRS Part III Total Score (in "On" State for the ROP+L-Dopa Group) at Week 52 and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. Percent change from baseline was calculated as (change from baseline score/baseline score) * 100; change from baseline was calculated as thescore at the observation day minus the baseline score. | Baseline, Week 52, and FAP (up to Week 52) |
| Japanese UPDRS Part IV Mean Total Score at Baseline, Week 52, and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. | Baseline, Week 52, and FAP (up to Week 52) |
| Mean Percent Change From Baseline in the Japanese UPDRS Part IV Total Score at Week 52 and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. Percent change from baseline was calculated as (change from baseline score/baseline score) * 100; change from baseline was calculated as thescore at the observation day minus the baseline score. | Baseline, Week 52, and FAP (up to Week 52) |
| Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group | The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. LOCF was used for the FAP data to impute post-baseline missing values. Some participants in each state were not included at FAP as having no post-baseline data in the corresponding state or having no data in the corresponding state at Week 52/withdrawal. | Baseline, Week 52, and FAP (up to Week 52) |
| Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group | The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. | Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group |
| Mean Change From Baseline in the Schwab and England Activities of Daily Living Scale Score by Clinician at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group | The Schwab and England Activities of Daily Living Scale Score is measured as percentage, from 100% (Completely independent. Able to do all chores without slowness, difficulty or impairment. Essentially normal. Unaware of any difficulty) to 0% (Vegetative functions such as swallowing, bladder and bowel functions are not functioning. Bedridden). | Baseline, Week 52, and FAP (up to Week 52) |
| Mean Change From Baseline in the Schwab and England Activities of Daily Living Scale Score by Clinician at Week 52 and FAP in ROP Group | The Schwab and England Activities of Daily Living Scale Score is measured as percentage, from 100% (Completely independent. Able to do all chores without slowness, difficulty or impairment. Essentially normal. Unaware of any difficulty) to 0% (Vegetative functions such as swallowing, bladder and bowel functions are not functioning. Bedridden). | Baseline, Week 52, and FAP (up to Week 52) |
| Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group | The percentage of participants remaining in the study was presented by Kaplan-Meier method, where premature discontinuation (i.e., withdrawal before Week 52) was the event, and participants who had completed the study were censored. | Days 0-422 |
| Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group | The percentage of participants remaining in the study was presented by Kaplan-Meier method, where premature discontinuation (i.e., withdrawal before Week 52) was the event, and participants who had completed the study were censored. | Days 0-419 |
| Number of Participants Scored as Responders on the Clinician's Global Impression (CGI) Scale at Week 52 and FAP | CGI is measured on the following 7-point scale: 1, Very much improved; 2, Much Improved; 3, Minimally improved; 4, No change; 5, Minimally worse; 6, Much worse; and 7, Very much worse. Responders are defined as those participants scored as "very much improved" or "much improved." | Week 52 and FAP (up to Week 52) |
| Mean Change From Baseline in Awake Time "Off" (Hours) and Awake Time "On" (Hours) at Week 52 and FAP in the ROP+L-Dopa Group Excluding Participants With "0" Off (Hour) at Baseline | "Off" state is where PD symptoms are not adequately controlled by the drug. "On" state is where PD symptoms are well controlled by the drug. The "off's" duration (awake time spent "off") and the "on's" duration (awake time spent "on") on each day were calculated. | Baseline, Week 52, and FAP (up to Week 52) |
| Fukuoka |
| 814-0180 |
| Japan |
| GSK Investigational Site | Fukuoka | 816-0943 | Japan |
| GSK Investigational Site | Fukuoka | 819-8585 | Japan |
| GSK Investigational Site | Hyōgo | 651-2273 | Japan |
| GSK Investigational Site | Ibaraki | 300-0053 | Japan |
| GSK Investigational Site | Kanagawa | 247-8533 | Japan |
| GSK Investigational Site | Kanagawa | 253-8558 | Japan |
| GSK Investigational Site | Kyoto | 616-8255 | Japan |
| GSK Investigational Site | Miyagi | 982-8555 | Japan |
| GSK Investigational Site | Miyagi | 989-2202 | Japan |
| GSK Investigational Site | Numakunai | 020-8505 | Japan |
| GSK Investigational Site | Osaka | 543-8555 | Japan |
| GSK Investigational Site | Osaka | 558-8558 | Japan |
| GSK Investigational Site | Osaka | 578-8588 | Japan |
| GSK Investigational Site | Osaka | 590-0132 | Japan |
| GSK Investigational Site | Osaka | 598-0048 | Japan |
| GSK Investigational Site | Saga | 849-8501 | Japan |
| GSK Investigational Site | Saitama | 364-8501 | Japan |
| GSK Investigational Site | Tokyo | 154-8551 | Japan |
| GSK Investigational Site | Tokyo | 160-0017 | Japan |
| GSK Investigational Site | Tokyo | 187-8551 | Japan |
| Protocol Violation |
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| Withdrawal by Subject |
|
| BG001 | Ropinirole Hydrochloride | Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | participants |
|
| ID | Title | Description |
|---|
| OG000 | ROP+L-Dopa | Participants received ropinirole hydrochloride (ROP) tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 milligrams (mg)/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. The dosing regimen of L-dopa remained unchanged from 4 weeks prior to the start of the Screening Phase throughout the study. |
| OG001 | Ropinirole Hydrochloride | Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study. |
|
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| Secondary | Mean Change From Baseline in the Japanese UPDRS Part I Total Score at Week 52 and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. This participant as well as those prematurely withdrawn from the study in each group was not included at Week 52. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 52, and FAP (up to Week 52) |
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| Secondary | Mean Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. "Off" state is where PD symptoms are not adequately controlled by the drug. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. Some participants were not included at FAP as having no post-baseline data in "on" state, not having "off" state at baseline, or no data in "off" state at Week 52/withdrawal. These participants as well as those prematurely withdrawn were not included at Week 52. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 52, and FAP (up to Week 52) |
|
|
|
| Secondary | Mean Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP in the ROP Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants prematurely withdrawn from the study were not included at Week 52. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 52, and FAP (up to Week 52) |
|
|
|
| Secondary | Mean Change From Baseline in the Japanese UPDRS Part IV Total Score at Week 52 and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. This participant as well as those prematurely withdrawn from the study in each group was not included at Week 52. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 52, and FAP (up to Week 52) |
|
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| Secondary | Japanese UPDRS Part I Mean Total Score at Baseline, Week 52, and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. This participant as well as those prematurely withdrawn from the study in each group was not included at Week 52. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 52, and FAP (up to Week 52) |
|
|
|
| Secondary | Mean Percent Change From Baseline in the Japanese UPDRS Part I Total Score at Week 52 and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part I assesses mentation, behavior, and mood on 4 items. Participants receive a score of 0-4 points per item. The maximum total score is 16 points. A higher score indicates more severe mental symptoms. Percent change from baseline was calculated as (change from baseline score/baseline score) * 100; change from baseline was calculated as thescore at the observation day minus the baseline score. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. Some participants were not included at FAP as having a baseline value of zero, which could not be used for calculating the percent change, or having no post-baseline data. These participants as well as those prematurely withdrawn in each group were not included at Week 52. | Posted | Mean | Standard Deviation | percent change in score | Baseline, Week 52, and FAP (up to Week 52) |
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| Secondary | Japanese UPDRS Part II Mean Total Score at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. "Off" state is where PD symptoms are not adequately controlled by the drug. LOCF was used for the FAP data. Some participants were not included at FAP as having no post-baseline data in "on" state or having no data in "off" state at Week 52/withdrawal. | FAS. Participants without "off" state at baseline were not included in the analysis of baseline "off" state data. Participants not included at FAP as well as those prematurely withdrawn from the study were not included at Week 52. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 52, and FAP (up to Week 52) |
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| Secondary | Japanese UPDRS Part II Mean Total Score at Baseline, Week 52, and FAP in ROP Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants prematurely withdrawn from the study were not included at Week 52. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 52, and FAP (up to Week 52) |
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| Secondary | Mean Percent Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. "Off" state is where PD symptoms are not adequately controlled by the drug. Percent change from baseline was calculated as (change from baseline score/baseline score) * 100; change from baseline was calculated as thescore at the observation day minus the baseline score. | FAS. LOCF was used for FAP data. Some participants were not included at FAP as having a baseline value of zero, having no post-baseline data in "on" state, not having "off" state at baseline in "off" state, or having no data at Week 52/withdrawal in "off" state. These participants as well as those prematurely withdrawn were not included at Week 52. | Posted | Mean | Standard Deviation | percent change in score | Baseline, Week 52, and FAP (up to Week 52) |
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|
| Secondary | Mean Percent Change From Baseline in the Japanese UPDRS Part II Total Score at Week 52 and FAP in the ROP Group | The Japanese UPDRS assesses the status of PD patients objectively. Part II assesses activities of daily living on 13 items. Participants receive a score of 0-4 points per item. The maximum total score is 52 points. A higher score indicates more severe PD symptoms. Percent change from baseline was calculated as (change from baseline score/baseline score) * 100; change from baseline was calculated as thescore at the observation day minus the baseline score. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. Some participants were not included at FAP as having a baseline value of zero, which could not be used for calculating the percent change. These participants as well as those prematurely withdrawn were not included at Week 52 | Posted | Mean | Standard Deviation | percent change in score | Baseline, Week 52, and FAP (up to Week 52) |
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|
| Secondary | Japanese UPDRS Part III Mean Total Score (in "On" State for the ROP+L-Dopa Group) at Baseline, Week 52, and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. | FAS. Participants having "off" state at baseline were not included in the ROP+L-dopa group at baseline. The participant not included in the FAP as well as one having "off" state in the ROP+L-dopa group at Week 52 and those prematurely withdrawn in each group were not included at Week 52. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 52, and FAP (up to Week 52) |
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|
| Secondary | Mean Percent Change From Baseline in the Japanese UPDRS Part III Total Score (in "On" State for the ROP+L-Dopa Group) at Week 52 and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part III assesses motor examination on 27 items. Participants receive a score of 0-4 points per item. The maximum total score is 108 points. A higher score indicates more severe PD symptoms. "On" state is where PD symptoms are well controlled by the drug. Percent change from baseline was calculated as (change from baseline score/baseline score) * 100; change from baseline was calculated as thescore at the observation day minus the baseline score. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants with "off" state at baseline or without post-baseline data were not included in the ROP+L-dopa group at FAP. These participants as well as one with "off" state at Week 52 in that group and those prematurely withdrawn in each group were not included at Week 52. | Posted | Mean | Standard Deviation | percent change in score | Baseline, Week 52, and FAP (up to Week 52) |
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|
| Secondary | Japanese UPDRS Part IV Mean Total Score at Baseline, Week 52, and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. This participant as well as those prematurely withdrawn from the study in each group was not included at Week 52. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Week 52, and FAP (up to Week 52) |
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|
|
| Secondary | Mean Percent Change From Baseline in the Japanese UPDRS Part IV Total Score at Week 52 and FAP | The Japanese UPDRS assesses the status of PD patients objectively. Part IV assesses complications of therapy on 11 items. Participants receive a score of 0-4 or 0-1 points per item depending on the item. The maximum total score is 23 points. A higher score indicates more severe symptoms of complications. Percent change from baseline was calculated as (change from baseline score/baseline score) * 100; change from baseline was calculated as thescore at the observation day minus the baseline score. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. Some participants were not included at FAP as having a baseline value of zero, which could not be used for calculating the percent change, or having no post-baseline data. These participants as well as those prematurely withdrawn from the study were not included at Week 52. | Posted | Mean | Standard Deviation | percent change in score | Baseline, Week 52, and FAP (up to Week 52) |
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| Secondary | Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP by "On"/"Off" State in the ROP+L-Dopa Group | The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. LOCF was used for the FAP data to impute post-baseline missing values. Some participants in each state were not included at FAP as having no post-baseline data in the corresponding state or having no data in the corresponding state at Week 52/withdrawal. | FAS. Participants without "off" state at baseline were not included in the analysis of baseline "off" state data. Participants not included at FAP as well as those prematurely withdrawn from the study were not included at Week 52. | Posted | Number | participants | Baseline, Week 52, and FAP (up to Week 52) |
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|
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| Secondary | Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group | The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease; 2.5, Mild bilateral disease; 3, Mild to moderate bilateral disease; 4, Severe disability; and 5, Wheelchair bound or bedridden unless aided. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants prematurely withdrawn from the study were not included at Week 52. | Posted | Number | participants | Number of Participants at Each Stage of the Modified Hoehn & Yahr Scale at Baseline, Week 52, and FAP in the ROP Group |
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|
|
| Secondary | Mean Change From Baseline in the Schwab and England Activities of Daily Living Scale Score by Clinician at Week 52 and FAP by "On"/"Off" State in the ROP+L-Dopa Group | The Schwab and England Activities of Daily Living Scale Score is measured as percentage, from 100% (Completely independent. Able to do all chores without slowness, difficulty or impairment. Essentially normal. Unaware of any difficulty) to 0% (Vegetative functions such as swallowing, bladder and bowel functions are not functioning. Bedridden). | FAS. LOCF was used for the FAP data. Some participants were not included at FAP as having no post-baseline data in "on" state, not having "off" state at baseline in "off" state, or having no data in the corresponding state at Week 52/withdrawal. These participants as well as those prematurely withdrawn were not included at Week 52. | Posted | Mean | Standard Deviation | percent change | Baseline, Week 52, and FAP (up to Week 52) |
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|
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| Secondary | Mean Change From Baseline in the Schwab and England Activities of Daily Living Scale Score by Clinician at Week 52 and FAP in ROP Group | The Schwab and England Activities of Daily Living Scale Score is measured as percentage, from 100% (Completely independent. Able to do all chores without slowness, difficulty or impairment. Essentially normal. Unaware of any difficulty) to 0% (Vegetative functions such as swallowing, bladder and bowel functions are not functioning. Bedridden). | FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants prematurely withdrawn from the study were not included at Week 52. | Posted | Mean | Standard Deviation | percent change | Baseline, Week 52, and FAP (up to Week 52) |
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| Secondary | Percentage of Participants Remaining in the Study on the Indicated Days in the ROP+L-Dopa Group | The percentage of participants remaining in the study was presented by Kaplan-Meier method, where premature discontinuation (i.e., withdrawal before Week 52) was the event, and participants who had completed the study were censored. | FAS | Posted | Number | percentage of participants | Days 0-422 |
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| Secondary | Percentage of Participants Remaining in the Study on the Indicated Days in the ROP Group | The percentage of participants remaining in the study was presented by Kaplan-Meier method, where premature discontinuation (i.e., withdrawal before Week 52) was the event, and participants who had completed the study were censored. | FAS | Posted | Number | percentage of participants | Days 0-419 |
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| Secondary | Number of Participants Scored as Responders on the Clinician's Global Impression (CGI) Scale at Week 52 and FAP | CGI is measured on the following 7-point scale: 1, Very much improved; 2, Much Improved; 3, Minimally improved; 4, No change; 5, Minimally worse; 6, Much worse; and 7, Very much worse. Responders are defined as those participants scored as "very much improved" or "much improved." | FAS. LOCF was used for the FAP data to impute post-baseline missing values. One participant was not included in the ROP+L-dopa group at FAP as having no post-baseline data. This participant as well as those prematurely withdrawn from the study in each group was not included at Week 52. | Posted | Number | participants | Week 52 and FAP (up to Week 52) |
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| Secondary | Mean Change From Baseline in Awake Time "Off" (Hours) and Awake Time "On" (Hours) at Week 52 and FAP in the ROP+L-Dopa Group Excluding Participants With "0" Off (Hour) at Baseline | "Off" state is where PD symptoms are not adequately controlled by the drug. "On" state is where PD symptoms are well controlled by the drug. The "off's" duration (awake time spent "off") and the "on's" duration (awake time spent "on") on each day were calculated. | FAS. LOCF was used for the FAP data to impute post-baseline missing values. Participants having "off" hour of zero at baseline were not included at FAP. These participants as well as those prematurely withdrawn from the study were not included at Week 52. | Posted | Mean | Standard Deviation | hours | Baseline, Week 52, and FAP (up to Week 52) |
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|
|
| 7 |
| 65 |
| 42 |
| 65 |
| EG001 | Ropinirole Hydrochloride | Participants received ROP tablets 3 times daily. In the 4-week Fixed Titration Phase (from Week 0 as Baseline), the dose started at 0.75 mg/day was increased weekly by 0.75 mg/day up to 3.0 mg/day. In the 48-week Flexible Titration and Maintenance Phase, the dose was increased by 1.5 mg/day at intervals at least 1 week up to a maximum of 15.0 mg/day. The dose was maintained at a level without further symptomatic improvement expected. Concomitant use of L-dopa was prohibited during the study. | 3 | 58 | 43 | 58 |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
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| Parkinson's Disease | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Sudden onset of sleep | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 12.1 | Systematic Assessment |
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| Cataract | Eye disorders | MedDRA 12.1 | Systematic Assessment |
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| Pyelonephritis | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
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| Dehydration | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
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| Gastric cancer recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 12.1 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Parkinson's Disease | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Sudden onset of sleep | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Dyskinesia | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Tremor | Nervous system disorders | MedDRA 12.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 12.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
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| Dental caries | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
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| Stomatitis | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA 12.1 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 12.1 | Systematic Assessment |
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| Hallucination | Psychiatric disorders | MedDRA 12.1 | Systematic Assessment |
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| Orthostatic hypotension | Vascular disorders | MedDRA 12.1 | Systematic Assessment |
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| Contusion | Injury, poisoning and procedural complications | MedDRA 12.1 | Systematic Assessment |
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| Decreased appetite | Metabolism and nutrition disorders | MedDRA 12.1 | Systematic Assessment |
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GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
| D009422 | Nervous System Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D019636 | Neurodegenerative Diseases |
| FAP, n=64, 58 |
|
| FAP, n=64, 26 |
|
| Title | Measurements |
|---|---|
|
| FAP, n=64, 58 |
|
| FAP, n=64, 58 |
|
| Baseline, n=65, 27, Stage 1.5 |
|
| Baseline, n=65, 27, Stage 2 |
|
| Baseline, n=65, 27, Stage 2.5 |
|
| Baseline, n=65, 27, Stage 3 |
|
| Baseline, n=65, 27, Stage 4 |
|
| Baseline, n=65, 27, Stage 5 |
|
| Week 52, n=47, 16, Stage 0 |
|
| Week 52, n=47, 16, Stage 1 |
|
| Week 52, n=47, 16, Stage 1.5 |
|
| Week 52, n=47, 16, Stage 2 |
|
| Week 52, n=47, 16, Stage 2.5 |
|
| Week 52, n=47, 16, Stage 3 |
|
| Week 52, n=47, 16, Stage 4 |
|
| Week 52, n=47, 16, Stage 5 |
|
| FAP, n=63, 25, Stage 0 |
|
| FAP, n=63, 25, Stage 1 |
|
| FAP, n=63, 25, Stage 1.5 |
|
| FAP, n=63, 25, Stage 2 |
|
| FAP, n=63, 25, Stage 2.5 |
|
| FAP, n=63, 25, Stage 3 |
|
| FAP, n=63, 25, Stage 4 |
|
| FAP, n=63, 25, Stage 5 |
|
| Title | Measurements |
|---|---|
|
| Baseline, n=58, Stage 2 |
|
| Baseline, n=58, Stage 2.5 |
|
| Baseline, n=58, Stage 3 |
|
| Baseline, n=58, Stage 4 |
|
| Baseline, n=58, Stage 5 |
|
| Week 52, n=46, Stage 0 |
|
| Week 52, n=46, Stage 1 |
|
| Week 52, n=46, Stage 1.5 |
|
| Week 52, n=46, Stage 2 |
|
| Week 52, n=46, Stage 2.5 |
|
| Week 52, n=46, Stage 3 |
|
| Week 52, n=46, Stage 4 |
|
| Week 52, n=46, Stage 5 |
|
| FAP, n=58, Stage 0 |
|
| FAP, n=58, Stage 1 |
|
| FAP, n=58, Stage 1.5 |
|
| FAP, n=58, Stage 2 |
|
| FAP, n=58, Stage 2.5 |
|
| FAP, n=58, Stage 3 |
|
| FAP, n=58, Stage 4 |
|
| FAP, n=58, Stage 5 |
|
| Title | Measurements |
|---|
|
| Day 43 |
|
| Day 85 |
|
| Day 101 |
|
| Day 112 |
|
| Day 128 |
|
| Day 154 |
|
| Day 169 |
|
| Day 196 |
|
| Day 203 |
|
| Day 238 |
|
| Day 282 |
|
| Day 301 |
|
| Day 341 |
|
| Day 365 |
|
| Day 422 |
|
| Title | Measurements |
|---|
|
| Day 36 |
|
| Day 66 |
|
| Day 71 |
|
| Day 85 |
|
| Day 167 |
|
| Day 169 |
|
| Day 175 |
|
| Day 210 |
|
| Day 241 |
|
| Day 253 |
|
| Day 419 |
|