Parkinson Disease
Conditions
Brief summary
This is a double blind, fixed dose, parallel group study to characterize the dose response of ropinirole PR as adjunctive therapy to L-dopa in patients with late stage Parkinson's disease. The primary endpoint of this study, mean change from baseline in total awake time spent off' is the same endpoint as used in the ropinirole PR pivotal study for advanced Parkinson's disease patients. This study includes a wide range of ropinirole doses (4-24mg) with the 8mg, 12mg, and 16mg per day doses powered to detect a 1.7 hour difference in total awake time spent off compared with placebo. The dose of Ldopa will remain stable through the study, unless the subject experiences tolerability issues that require an L-dopa dose reduction. Up to three L-dopa dose reductions are allowed, making a total reduction of up to approximately 30%. Keeping the L-dopa dose constant where possible is important to avoid confounding the efficacy data. Clinical review of the primary and secondary endpoints will be performed in order to establish the lowest maximally effective therapeutic dose.
Interventions
DRUGropinirole/L-dopa
Ropinirole as adjunctive therapy with L-dopa
DRUGplacebo/L-dopa
Placebo as adjunctive therapy with L-dopa
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of idiopathic Parkinson's disease (according to modified Hoehn & Yahr criteria Stages II-IV) and demonstrating lack of control with L-dopa therapy (e.g. end of dose akinesia, simple on/off fluctuations). * Subjects receiving a stable dose of L-dopa for at least 4 weeks prior to screening. * A minimum of 3 hours awake off-time for each diary day recorded during the baseline period. * Men or non-pregnant/non-breast-feeding women of at least 30 years of age at screening. Women of child-bearing potential must be practicing a clinically accepted method of contraception during the study and for at least one month prior to randomization and one month following completion of the study. Acceptable contraceptive methods include abstinence, oral contraception, injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, surgical sterilisation, male partner sterilization, intrauterine device \[IUD\], or double barrier method: condom or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/gel/film/cream/suppository. * Provide written informed consent for this study. * Be willing and able to comply with study procedures, including diary card completion and follow-up clinic visits.
Exclusion criteria
* Late stage advanced subjects demonstrating incapacitating peak dose or diphasic dyskinesia on their stable dose of L-dopa * Consumption of any dopamine agonist, including ropinirole, within four weeks of randomization in the study. * Subjects with severe, clinically significant condition(s) other than Parkinson's disease which, in the opinion of the investigator, would render the subject unsuitable for the study (e.g., psychiatric, haematological, renal, hepatic, endocrinology, neurological \[other than Parkinson's disease\], cardiovascular, or active malignancy \[other than basal cell carcinoma\]). * Subjects with crippling degenerative arthritis or other physical or mental conditions which would preclude accurate assessment of efficacy or safety. * Subjects with prior or current major psychosis (e.g., schizophrenia or psychotic depression) e.g. scoring 3 or 4 on UPDRS item 2 \[thought disorder\] or item 3 \[depression\]. * Subjects with severe clinical dementia e.g. scoring 3 or 4 on UPDRS item 1 \[mentation\]. * Subjects with severe dizziness or fainting due to postural hypotension on standing. * Subjects with a personal history of melanoma. * Subjects with clinically significant abnormalities in laboratory or ECG tests at Screening. If findings are outside the normal range and the subject is included, it must be documented by the investigator that the findings are not of clinical significance. * Subjects who are diagnosed with an impulse control disorder. The modified MIDI will be conducted at screening. Subjects who score positive for this screen must be referred to a specialist for diagnostic evaluation. * Subjects who have an active suicidal plan/intent or have had active suicidal thoughts in the past 6 months. Subjects who have a history of suicide attempt in the last 2 years or more than 1 lifetime suicide attempt. * Current alcohol or drug dependence. * Definite or suspected personal or family history of clinically significant adverse reactions or hypersensitivity to ropinirole (or to drugs with a similar chemical structure) that would preclude long-term dosing with ropinirole. * Withdrawal, introduction, or change in dose of hormone replacement therapy and/or any drug known to substantially inhibit CYP1A2 (e.g. ciprofloxacine, fluvoxamine, cimetidine, ethinyloestradiol) or induce CYP1A2 (e.g. tobacco, omeprazole) within 7 days prior to enrolment (randomization). Subjects already on chronic therapy with any of these agents may be enrolled but doses must have remained stable from 7 days prior to enrolment (randomization) through the end of the treatment period. * Women who are pregnant or breast-feeding. * Use of an investigational drug from 30 days or 5 half-lives (whichever is longer) prior to enrolment (randomization) through to the end of the treatment period. 15. Women who are pregnant or breast-feeding. 16. Use of an investigational drug from 30 days or 5 half-lives (whichever is longer) prior to enrolment (randomization) through to the end of the treatment period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (BL) in Total Awake Time Spent Off at Week 4 of Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Off time is defined as the state in which the participants(par) symptoms include lack of mobility(bradykinesia) with or without additional features such as tremor or rigidity. Par were asked to record awake time off , awake time on, troublesome dyskinesias(TD) during awake time on, or time asleep for 30 minute intervals in 24 hr diary cards for 2 days preceding visits. Total number of awake hrs spent off per 24-hr period was the average of the 2 diary cards of the sum of awake hours spent off in each 24-hr diary card. BL is the last non-missing assessment measured on or before the first dose, change from BL was calculated by subtracting the BL values from the MP Week 4 values. Mixed Model Repeated Measures (MMRM) model used BL total awake time 'Off', treatment, visit and treatment by visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a >=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. Percentage of participants meeting the criterion (LS mean on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline 'off-time', treatment, visit and treatment\*visit are included in the model. |
| Percentage of Participants With a >=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. Percentage of participants meeting the criterion (LS mean on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline 'off-time', treatment, visit and treatment\*visit are included in the model. |
| Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period | Week 4 of the Maintenance Period (Study Week 17) | The CGI-I scale allows the investigator to rate the participant's total improvement since the beginning of treatment (Baseline). Baseline is defined as the last non-missing assessment measured on or before the first dose date. The scale is rated from 1-7 where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The responder rate is defined as the percentage of participants with a score of 1 or 2. The Generalized Estimating Equations (GEE) model was used to determine CGI responder rate with treatment, visit, and treatment by visit interaction included in the model. Only scheduled visits were included. |
| Change From Baseline in Absolute Awake Time Spent on Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Dyskinesias are involuntary twisting, turning movements caused by medication during on time in Parkinson's Disease (PD). TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit. The total number of awake hours spent on without TD per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on without TD in each 24 hour diary card. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from Mixed Model Repeated Measures (MMRM). Par with a non-missing efficacy observation at BL and during the MP were analyzed. |
| Change From Baseline in Absolute Awake Time Spent on at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of the awake hours spent on in each 24 hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Percent Change From Baseline in Awake Time Spent Off at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | The off state is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia), with or without additional features such as tremor or rigidity. Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent off per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent off in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values multiplied (×) the results with 100. LS means, 95% CIs and P-values were estimated from MMRM. |
| Percent Change From Baseline in Awake Time Spent on Without TD at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Dyskinesias are involuntary twisting, turning movements caused by medication during on time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on without TD per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on without TD in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values × 100. LS means, 95% CIs and P-values were estimated from MMRM. |
| Percent Change From Baseline in Awake Time Spent on at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Par. were asked to recordawake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values × 100. LS means, 95% CIs and P-values were estimated from MMRM. |
| Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL value × 100. LS means, 95% CIs and P-values were estimated from MMRM. |
| Change From Baseline in the Percent Awake Time Spent Off at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | The off state is defined as the state in which the participants' symptoms include lack of mobility(bradykinesia), with or without additional features such as tremor or rigidity. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent off per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent off in each 24-hour diary card. The percentage of awake time spent off= Awake time spent off divided by (Awake time spent off + Awake time spent on) × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) Off Time at Week-4 of Maintenance Period | Week 4 of the Maintenance Period (Study Week 17) | The responder rate was defined as the percentage of par with greater than or equal to (\>=) 20 percent (%) reduction in their individual BL off time at Week 4 of the Maintenance Period. The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. Responder Rate (Least Squares \[LS\] means on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline total awake time 'Off', treatment, visit and treatment\*visit are included in the model. |
| Change From Baseline in the Percent Awake Time Spent on at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on in each 24-hour diary card. The percentage of awake time spent on= Awake time spent on divided by (Awake time spent on + Awake time spent off) × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an on State, at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | The UPDRS Part II is the ADL score and can range from 0 to 52 as determined by the physician. The higher score indicates the worse condition. Test were performed when the par. is in the on state of PD. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Change From Baseline in the Percent of a 24-hour Day Spent Off at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | The off state is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia), with or without additional features such as tremor or rigidity. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of day awake hours spent off per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent off in each 24-hour diary card. The percentage of 24 hour day spent off= awake time spent off divided by 24 x 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Change From Baseline in the Percent of a 24- Hour Day Spent on Without TD at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Dyskinesias are involuntary twisting, turning movements caused by medication during on time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hr diary cards for the 2 days preceding each visit. The total number of day awake hr spent on without TD per 24-hr period was the average across the 2 diary cards of the sum of awake hours spent on without TD in each 24-hour diary card. The percentage of 24 hr day spent on without TD= awake time spent on without TD divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date, change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Change From Baseline in the Percent of a 24-hour Day Spent on at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of day awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on in each 24-hour diary card. The percentage of a 24-hour day spent on = Awake time spent on divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. The percentage of a 24-hour day spent asleep during the night time hours = Total sleep hours during the night time hours of sleep divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an on State, at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the par.. One of the six features include the Part III-motor examination where scores can range 0 to 108 with par. in an on state where the maximum score indicates the worse condition. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Change From Baseline in UPDRS ADL Score With Participants in an Off State, at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | The UPDRS Part II is the ADL score and can range from 0 to 52 as determined by the physician. The higher score indicates the worse condition. Test was performed when the par is in the off state of PD. The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period | Baseline (BL) and Week 4 of the Maintenance Period (Study Week 17) | The UPDRS Part I scores mentation, behavior and mood as determined by a physician and par. were tested during the on phase of PD. This component of the UPDRS is the total score for 4 items (the items 1 to 4 include intellectual impairment, thought disorder, motivation / initiative, and depression) and may have a value ranging from 0 to 16 as determined by a physician. The higher score (16) indicates the maximum score and the worse condition. All 4 items have to be present for a total score to be calculated. If one or more items are missing, the total score for the component would also be missing. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the individual post-randomization values. LS means, 95% CIs and P-values were estimated from MMRM. |
| Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy | From start of study treatment until end of treatment (assessed up to 18 weeks) | The percentage of participants who withdrew from the study due to lack of efficacy as defined by either the participant or the investigator is presented here. All participants with a non-missing efficacy observation at Baseline and at least one post-Baseline efficacy assessment at any time during the study were analyzed. |
| Change From Baseline in the Percent Awake Time Spent on Without TD at Week 4 of the Maintenance Period | Baseline and Week 4 of the Maintenance Period (Study Week 17) | Dyskinesias are involuntary twisting, turning movements caused by medication during on time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hr diary cards for the 2 days preceding each visit of the study. The total number of awake hr spent on without TD per 24-hr period was the average across the 2 diary cards of the sum of awake hr spent on without TD in each 24-hr diary card. Percentage of awake time spent onwithout TD= Awake time spent on without TD divided by(Awake time spent on + Awake time spent off) × 100. BL is defined as the last non-missing assessment measured on or before the first dose date, change from BL was calculated by subtracting BL values from MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM. |
Countries
Argentina, Chile, Estonia, Russia, Slovakia, South Korea, United States
Participant flow
Recruitment details
Eligible participants(par) were diagnosed with advanced stage idiopathic Parkinson's Disease (PD), demonstrated lack of control with Levo(L)-dopa therapy, and on a stable dose of L-dopa for a minimum of 4 weeks prior to screening. Par were randomized into one of six treatment arms to receive placebo or ropinirole prolonged release(PR) tablets.
Pre-assignment details
After screening, par underwent a 13 Week up-titration period until reaching their target dose then continued on their target dose during a 4 Week Maintenance Period up to Week 17. All par underwent a 1 Week down-titration period and then a follow-up visit 2 Weeks after receiving the last dose of study medication.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Group A: Placebo Participants (par.) were administered a matching prolonged release (PR) placebo tablet once daily (OD) for up to 17 Weeks. Par. completed a follow-up visit 2 weeks after receiving the last dose of study medication. | 75 |
| Treatment Group B: 4 mg/Day Par. were administered a ropinirole PR tablet totalling 2 milligrams per day (mg/day), OD for one week. Par. were up-titrated to 4 mg/day at Week 2 and continued this dose up to study Week 17. Par. reaching their target dose and completing the Maintenance Period or withdrawing prematurely were switched to placebo for down-titration for 1 Week before completing a follow-up visit 2 weeks after receiving the last dose of study medication. | 25 |
| Treatment Group C: 8 mg/Day Par. were administered a ropinirole PR tablet totalling 2 mg/day, OD for one week. Par. were up-titrated to 4 mg/day at Week 2, 6 mg/day at Week 3, and 8 mg/day at Week 4. Par. continued this dose up to study Week 17. Par. reaching their target dose and completing the Maintenance Period or withdrawing prematurely were switched to ropinirole PR 6.0 mg/day for 4 days then 4.0 mg/day for 3 days for down-titration before completing a follow-up visit 2 weeks after receiving the last dose of study medication. | 76 |
| Treatment Group D: 12 mg/Day Par. were administered a ropinirole PR tablet totalling 2 mg/day, OD for one week. Par. were up-titrated to 4 mg/day at Week 2, 6 mg/day at Week 3, 8 mg/day at Week 4 and 12 mg/day at Week 6. Par. continued this dose up to study Week 17. Par. reaching their target dose and completing the Maintenance Period or withdrawing prematurely were switched to ropinirole PR 8.0 mg/day for 4 days then 4.0 mg/day for 3 days for down-titration before completing a follow-up visit 2 weeks after receiving the last dose of study medication. | 75 |
| Treatment Group E: 16 mg/Day Par. were administered a ropinirole PR tablet totalling 2 mg/day, OD for one week. Par. were up-titrated to 4 mg/day at Week 2, 6 mg/day at Week 3, 8 mg/day at Week 4, 12 mg/day at Week 6 and 16 mg/day at Week 8. Par. continued this dose up to study Week 17. Par. reaching their target dose and completing the Maintenance Period or withdrawing prematurely were switched to ropinirole PR 12.0 mg/day for 4 days then 6.0 mg/day for 3 days for down-titration before completing a follow-up visit 2 weeks after receiving the last dose of study medication. | 76 |
| Treatment Group F: 24 mg/Day Par. were administered a ropinirole PR tablet totalling 2 mg/day, OD for one week. Par. were up-titrated to 4 mg/day at Week 2, 6 mg/day at Week 3, 8 mg/day at Week 4, 12 mg/day at Week 6, 16 mg/day at Week 8, 20 mg/day at Week 10, and 24 mg/day at Week 12. Par. continued this dose up to study Week 17. Par. reaching their target dose and completing the maintenance or withdrawing prematurely were switched to ropinirole PR 16.0 mg/day for 4 days then 8.0 mg/day for 3 days for down-titration before completing a follow-up visit 2 weeks after receiving the last dose of study medication. | 25 |
| Total | 352 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 1 | 8 | 6 | 5 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Physician Decision | 0 | 1 | 1 | 2 | 0 | 0 |
| Overall Study | Protocol-defined stopping criteria | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Protocol deviation | 2 | 1 | 3 | 2 | 3 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 4 | 3 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Treatment Group F: 24 mg/Day | Treatment Group E: 16 mg/Day | Treatment Group D: 12 mg/Day | Treatment Group C: 8 mg/Day | Treatment Group B: 4 mg/Day | Treatment Group A: Placebo |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 64.8 Years STANDARD_DEVIATION 9.26 | 66.9 Years STANDARD_DEVIATION 7.94 | 63.7 Years STANDARD_DEVIATION 9.13 | 65.2 Years STANDARD_DEVIATION 9.62 | 65.6 Years STANDARD_DEVIATION 9.19 | 66.5 Years STANDARD_DEVIATION 7.45 | 63.7 Years STANDARD_DEVIATION 9.98 |
| Race/Ethnicity, Customized African American/African Heritage | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 20 Participants | 1 Participants | 6 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 3 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 325 Participants | 24 Participants | 69 Participants | 68 Participants | 73 Participants | 21 Participants | 70 Participants |
| Sex: Female, Male Female | 168 Participants | 10 Participants | 38 Participants | 33 Participants | 33 Participants | 12 Participants | 42 Participants |
| Sex: Female, Male Male | 184 Participants | 15 Participants | 38 Participants | 42 Participants | 43 Participants | 13 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 31 / 75 | 9 / 25 | 27 / 76 | 40 / 75 | 43 / 76 | 11 / 25 |
| serious Total, serious adverse events | 0 / 75 | 0 / 25 | 3 / 76 | 0 / 75 | 1 / 76 | 0 / 25 |
Outcome results
Primary
Change From Baseline (BL) in Total Awake Time Spent Off at Week 4 of Maintenance Period
Off time is defined as the state in which the participants(par) symptoms include lack of mobility(bradykinesia) with or without additional features such as tremor or rigidity. Par were asked to record awake time off , awake time on, troublesome dyskinesias(TD) during awake time on, or time asleep for 30 minute intervals in 24 hr diary cards for 2 days preceding visits. Total number of awake hrs spent off per 24-hr period was the average of the 2 diary cards of the sum of awake hours spent off in each 24-hr diary card. BL is the last non-missing assessment measured on or before the first dose, change from BL was calculated by subtracting the BL values from the MP Week 4 values. Mixed Model Repeated Measures (MMRM) model used BL total awake time 'Off', treatment, visit and treatment by visit
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: The Intent to Treat(ITT) Population included all randomized par who received at least one dose of study medication, had a BL efficacy assessment for the outcome, and at least one respective Post-BL efficacy assessment. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline (BL) in Total Awake Time Spent Off at Week 4 of Maintenance Period | -1.91 Hours |
| Treatment Group B: 4 mg/Day | Change From Baseline (BL) in Total Awake Time Spent Off at Week 4 of Maintenance Period | -2.04 Hours |
| Treatment Group C: 8 mg/Day | Change From Baseline (BL) in Total Awake Time Spent Off at Week 4 of Maintenance Period | -2.92 Hours |
| Treatment Group D: 12 mg/Day | Change From Baseline (BL) in Total Awake Time Spent Off at Week 4 of Maintenance Period | -2.34 Hours |
| Treatment Group E: 16 mg/Day | Change From Baseline (BL) in Total Awake Time Spent Off at Week 4 of Maintenance Period | -2.80 Hours |
| Treatment Group F: 24 mg/Day | Change From Baseline (BL) in Total Awake Time Spent Off at Week 4 of Maintenance Period | -2.37 Hours |
Comparison: 4mg/day vs Placebop-value: 0.814Mixed Models Analysis
Comparison: 8 mg/day vs Placebop-value: 0.013Mixed Models Analysis
Comparison: 12 mg/day vs Placebop-value: 0.287Mixed Models Analysis
Comparison: 16 mg/day vs Placebop-value: 0.027Mixed Models Analysis
Comparison: 24 mg/day vs Placebop-value: 0.39Mixed Models Analysis
Comparison: 4mg/day vs Placebop-value: 0.844ANCOVA
Comparison: 8 mg/day vs Placebop-value: 0.03ANCOVA
Comparison: 12 mg/day vs Placebop-value: 0.437ANCOVA
Comparison: 16 mg/day vs Placebop-value: 0.034ANCOVA
Comparison: 24 mg/day vs Placebop-value: 0.808ANCOVA
Secondary
Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period
Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period | 0.22 Hours |
| Treatment Group B: 4 mg/Day | Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period | 0.86 Hours |
| Treatment Group C: 8 mg/Day | Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period | 0.22 Hours |
| Treatment Group D: 12 mg/Day | Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period | 0.15 Hours |
| Treatment Group E: 16 mg/Day | Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period | 0.14 Hours |
| Treatment Group F: 24 mg/Day | Change From Baseline for Total Sleep Time During the Night Time Hours of Sleep at Week 4 of the Maintenance Period | 0.04 Hours |
p-value: 0.073Mixed Models Analysis
p-value: 0.996Mixed Models Analysis
p-value: 0.791Mixed Models Analysis
p-value: 0.747Mixed Models Analysis
p-value: 0.6Mixed Models Analysis
Secondary
Change From Baseline in Absolute Awake Time Spent on at Week 4 of the Maintenance Period
Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of the awake hours spent on in each 24 hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in Absolute Awake Time Spent on at Week 4 of the Maintenance Period | 1.70 Hours |
| Treatment Group B: 4 mg/Day | Change From Baseline in Absolute Awake Time Spent on at Week 4 of the Maintenance Period | 1.20 Hours |
| Treatment Group C: 8 mg/Day | Change From Baseline in Absolute Awake Time Spent on at Week 4 of the Maintenance Period | 2.69 Hours |
| Treatment Group D: 12 mg/Day | Change From Baseline in Absolute Awake Time Spent on at Week 4 of the Maintenance Period | 2.23 Hours |
| Treatment Group E: 16 mg/Day | Change From Baseline in Absolute Awake Time Spent on at Week 4 of the Maintenance Period | 2.62 Hours |
| Treatment Group F: 24 mg/Day | Change From Baseline in Absolute Awake Time Spent on at Week 4 of the Maintenance Period | 2.34 Hours |
p-value: 0.419Mixed Models Analysis
p-value: 0.026Mixed Models Analysis
p-value: 0.23Mixed Models Analysis
p-value: 0.033Mixed Models Analysis
p-value: 0.266Mixed Models Analysis
Secondary
Change From Baseline in Absolute Awake Time Spent on Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period
Dyskinesias are involuntary twisting, turning movements caused by medication during on time in Parkinson's Disease (PD). TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit. The total number of awake hours spent on without TD per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on without TD in each 24 hour diary card. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from Mixed Model Repeated Measures (MMRM). Par with a non-missing efficacy observation at BL and during the MP were analyzed.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in Absolute Awake Time Spent on Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period | 1.76 Hours |
| Treatment Group B: 4 mg/Day | Change From Baseline in Absolute Awake Time Spent on Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period | 1.21 Hours |
| Treatment Group C: 8 mg/Day | Change From Baseline in Absolute Awake Time Spent on Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period | 2.69 Hours |
| Treatment Group D: 12 mg/Day | Change From Baseline in Absolute Awake Time Spent on Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period | 2.16 Hours |
| Treatment Group E: 16 mg/Day | Change From Baseline in Absolute Awake Time Spent on Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period | 2.49 Hours |
| Treatment Group F: 24 mg/Day | Change From Baseline in Absolute Awake Time Spent on Without Troublesome Dyskinesia (TD) at Week 4 of the Maintenance Period | 2.24 Hours |
p-value: 0.376Mixed Models Analysis
p-value: 0.036Mixed Models Analysis
p-value: 0.362Mixed Models Analysis
p-value: 0.089Mixed Models Analysis
p-value: 0.403Mixed Models Analysis
Secondary
Change From Baseline in the Percent Awake Time Spent Off at Week 4 of the Maintenance Period
The off state is defined as the state in which the participants' symptoms include lack of mobility(bradykinesia), with or without additional features such as tremor or rigidity. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent off per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent off in each 24-hour diary card. The percentage of awake time spent off= Awake time spent off divided by (Awake time spent off + Awake time spent on) × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in the Percent Awake Time Spent Off at Week 4 of the Maintenance Period | -12.43 Percentage of off time in hours |
| Treatment Group B: 4 mg/Day | Change From Baseline in the Percent Awake Time Spent Off at Week 4 of the Maintenance Period | -11.60 Percentage of off time in hours |
| Treatment Group C: 8 mg/Day | Change From Baseline in the Percent Awake Time Spent Off at Week 4 of the Maintenance Period | -18.41 Percentage of off time in hours |
| Treatment Group D: 12 mg/Day | Change From Baseline in the Percent Awake Time Spent Off at Week 4 of the Maintenance Period | -15.36 Percentage of off time in hours |
| Treatment Group E: 16 mg/Day | Change From Baseline in the Percent Awake Time Spent Off at Week 4 of the Maintenance Period | -17.81 Percentage of off time in hours |
| Treatment Group F: 24 mg/Day | Change From Baseline in the Percent Awake Time Spent Off at Week 4 of the Maintenance Period | -15.01 Percentage of off time in hours |
p-value: 0.822Mixed Models Analysis
p-value: 0.025Mixed Models Analysis
p-value: 0.267Mixed Models Analysis
p-value: 0.039Mixed Models Analysis
p-value: 0.458Mixed Models Analysis
Secondary
Change From Baseline in the Percent Awake Time Spent on at Week 4 of the Maintenance Period
Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on in each 24-hour diary card. The percentage of awake time spent on= Awake time spent on divided by (Awake time spent on + Awake time spent off) × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in the Percent Awake Time Spent on at Week 4 of the Maintenance Period | 12.43 Percentage of on time in hours |
| Treatment Group B: 4 mg/Day | Change From Baseline in the Percent Awake Time Spent on at Week 4 of the Maintenance Period | 11.60 Percentage of on time in hours |
| Treatment Group C: 8 mg/Day | Change From Baseline in the Percent Awake Time Spent on at Week 4 of the Maintenance Period | 18.41 Percentage of on time in hours |
| Treatment Group D: 12 mg/Day | Change From Baseline in the Percent Awake Time Spent on at Week 4 of the Maintenance Period | 15.36 Percentage of on time in hours |
| Treatment Group E: 16 mg/Day | Change From Baseline in the Percent Awake Time Spent on at Week 4 of the Maintenance Period | 17.81 Percentage of on time in hours |
| Treatment Group F: 24 mg/Day | Change From Baseline in the Percent Awake Time Spent on at Week 4 of the Maintenance Period | 15.01 Percentage of on time in hours |
p-value: 0.822Mixed Models Analysis
p-value: 0.025Mixed Models Analysis
p-value: 0.267Mixed Models Analysis
p-value: 0.039Mixed Models Analysis
p-value: 0.458Mixed Models Analysis
Secondary
Change From Baseline in the Percent Awake Time Spent on Without TD at Week 4 of the Maintenance Period
Dyskinesias are involuntary twisting, turning movements caused by medication during on time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hr diary cards for the 2 days preceding each visit of the study. The total number of awake hr spent on without TD per 24-hr period was the average across the 2 diary cards of the sum of awake hr spent on without TD in each 24-hr diary card. Percentage of awake time spent onwithout TD= Awake time spent on without TD divided by(Awake time spent on + Awake time spent off) × 100. BL is defined as the last non-missing assessment measured on or before the first dose date, change from BL was calculated by subtracting BL values from MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in the Percent Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 12.89 Percentage of on time in hours |
| Treatment Group B: 4 mg/Day | Change From Baseline in the Percent Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 11.58 Percentage of on time in hours |
| Treatment Group C: 8 mg/Day | Change From Baseline in the Percent Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 18.34 Percentage of on time in hours |
| Treatment Group D: 12 mg/Day | Change From Baseline in the Percent Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 14.99 Percentage of on time in hours |
| Treatment Group E: 16 mg/Day | Change From Baseline in the Percent Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 17.05 Percentage of on time in hours |
| Treatment Group F: 24 mg/Day | Change From Baseline in the Percent Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 14.56 Percentage of on time in hours |
p-value: 0.734Mixed Models Analysis
p-value: 0.048Mixed Models Analysis
p-value: 0.443Mixed Models Analysis
p-value: 0.123Mixed Models Analysis
p-value: 0.641Mixed Models Analysis
Secondary
Change From Baseline in the Percent of a 24-hour Day Spent Off at Week 4 of the Maintenance Period
The off state is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia), with or without additional features such as tremor or rigidity. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of day awake hours spent off per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent off in each 24-hour diary card. The percentage of 24 hour day spent off= awake time spent off divided by 24 x 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in the Percent of a 24-hour Day Spent Off at Week 4 of the Maintenance Period | -7.94 Percentage of off time in hours |
| Treatment Group B: 4 mg/Day | Change From Baseline in the Percent of a 24-hour Day Spent Off at Week 4 of the Maintenance Period | -8.50 Percentage of off time in hours |
| Treatment Group C: 8 mg/Day | Change From Baseline in the Percent of a 24-hour Day Spent Off at Week 4 of the Maintenance Period | -12.17 Percentage of off time in hours |
| Treatment Group D: 12 mg/Day | Change From Baseline in the Percent of a 24-hour Day Spent Off at Week 4 of the Maintenance Period | -9.75 Percentage of off time in hours |
| Treatment Group E: 16 mg/Day | Change From Baseline in the Percent of a 24-hour Day Spent Off at Week 4 of the Maintenance Period | -11.65 Percentage of off time in hours |
| Treatment Group F: 24 mg/Day | Change From Baseline in the Percent of a 24-hour Day Spent Off at Week 4 of the Maintenance Period | -9.86 Percentage of off time in hours |
p-value: 0.027Mixed Models Analysis
p-value: 0.39Mixed Models Analysis
p-value: 0.814Mixed Models Analysis
p-value: 0.013Mixed Models Analysis
p-value: 0.287Mixed Models Analysis
Secondary
Change From Baseline in the Percent of a 24-hour Day Spent on at Week 4 of the Maintenance Period
Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of day awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on in each 24-hour diary card. The percentage of a 24-hour day spent on = Awake time spent on divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in the Percent of a 24-hour Day Spent on at Week 4 of the Maintenance Period | 7.08 Percentage of on time in hours |
| Treatment Group B: 4 mg/Day | Change From Baseline in the Percent of a 24-hour Day Spent on at Week 4 of the Maintenance Period | 4.99 Percentage of on time in hours |
| Treatment Group C: 8 mg/Day | Change From Baseline in the Percent of a 24-hour Day Spent on at Week 4 of the Maintenance Period | 11.20 Percentage of on time in hours |
| Treatment Group D: 12 mg/Day | Change From Baseline in the Percent of a 24-hour Day Spent on at Week 4 of the Maintenance Period | 9.28 Percentage of on time in hours |
| Treatment Group E: 16 mg/Day | Change From Baseline in the Percent of a 24-hour Day Spent on at Week 4 of the Maintenance Period | 10.94 Percentage of on time in hours |
| Treatment Group F: 24 mg/Day | Change From Baseline in the Percent of a 24-hour Day Spent on at Week 4 of the Maintenance Period | 9.76 Percentage of on time in hours |
p-value: 0.419Mixed Models Analysis
p-value: 0.026Mixed Models Analysis
p-value: 0.23Mixed Models Analysis
p-value: 0.033Mixed Models Analysis
p-value: 0.266Mixed Models Analysis
Secondary
Change From Baseline in the Percent of a 24- Hour Day Spent on Without TD at Week 4 of the Maintenance Period
Dyskinesias are involuntary twisting, turning movements caused by medication during on time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hr diary cards for the 2 days preceding each visit. The total number of day awake hr spent on without TD per 24-hr period was the average across the 2 diary cards of the sum of awake hours spent on without TD in each 24-hour diary card. The percentage of 24 hr day spent on without TD= awake time spent on without TD divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date, change from BL was calculated by subtracting the BL values from the MP Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in the Percent of a 24- Hour Day Spent on Without TD at Week 4 of the Maintenance Period | 7.32 Percentage of on time in hours |
| Treatment Group B: 4 mg/Day | Change From Baseline in the Percent of a 24- Hour Day Spent on Without TD at Week 4 of the Maintenance Period | 5.03 Percentage of on time in hours |
| Treatment Group C: 8 mg/Day | Change From Baseline in the Percent of a 24- Hour Day Spent on Without TD at Week 4 of the Maintenance Period | 11.19 Percentage of on time in hours |
| Treatment Group D: 12 mg/Day | Change From Baseline in the Percent of a 24- Hour Day Spent on Without TD at Week 4 of the Maintenance Period | 8.99 Percentage of on time in hours |
| Treatment Group E: 16 mg/Day | Change From Baseline in the Percent of a 24- Hour Day Spent on Without TD at Week 4 of the Maintenance Period | 10.40 Percentage of on time in hours |
| Treatment Group F: 24 mg/Day | Change From Baseline in the Percent of a 24- Hour Day Spent on Without TD at Week 4 of the Maintenance Period | 9.34 Percentage of on time in hours |
p-value: 0.376Mixed Models Analysis
p-value: 0.036Mixed Models Analysis
p-value: 0.362Mixed Models Analysis
p-value: 0.089Mixed Models Analysis
p-value: 0.403Mixed Models Analysis
Secondary
Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period
Par were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. The percentage of a 24-hour day spent asleep during the night time hours = Total sleep hours during the night time hours of sleep divided by 24 × 100. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period | 0.91 Percentage of time in hours |
| Treatment Group B: 4 mg/Day | Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period | 3.57 Percentage of time in hours |
| Treatment Group C: 8 mg/Day | Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period | 0.92 Percentage of time in hours |
| Treatment Group D: 12 mg/Day | Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period | 0.63 Percentage of time in hours |
| Treatment Group E: 16 mg/Day | Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period | 0.58 Percentage of time in hours |
| Treatment Group F: 24 mg/Day | Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep as a Percentage of a 24-hour Day, at Week 4 of the Maintenance Period | 0.18 Percentage of time in hours |
p-value: 0.073Mixed Models Analysis
p-value: 0.996Mixed Models Analysis
p-value: 0.791Mixed Models Analysis
p-value: 0.747Mixed Models Analysis
p-value: 0.6Mixed Models Analysis
Secondary
Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an on State, at Week 4 of the Maintenance Period
The UPDRS is a clinician based rating scale used to measure motor impairments and disability. The UPDRS assesses six features of PD impairment. These are evaluated using a combination of data collected by interview and examination of the par.. One of the six features include the Part III-motor examination where scores can range 0 to 108 with par. in an on state where the maximum score indicates the worse condition. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an on State, at Week 4 of the Maintenance Period | -4.75 Score on scale |
| Treatment Group B: 4 mg/Day | Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an on State, at Week 4 of the Maintenance Period | -10.38 Score on scale |
| Treatment Group C: 8 mg/Day | Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an on State, at Week 4 of the Maintenance Period | -8.43 Score on scale |
| Treatment Group D: 12 mg/Day | Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an on State, at Week 4 of the Maintenance Period | -8.34 Score on scale |
| Treatment Group E: 16 mg/Day | Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an on State, at Week 4 of the Maintenance Period | -8.86 Score on scale |
| Treatment Group F: 24 mg/Day | Change From Baseline in Unified Parkinson Disease Rating Scale (UPDRS) Motor Score With Participants in an on State, at Week 4 of the Maintenance Period | -10.06 Score on scale |
p-value: 0.007Mixed Models Analysis
p-value: 0.014Mixed Models Analysis
p-value: 0.016Mixed Models Analysis
p-value: 0.005Mixed Models Analysis
p-value: 0.008Mixed Models Analysis
Secondary
Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an on State, at Week 4 of the Maintenance Period
The UPDRS Part II is the ADL score and can range from 0 to 52 as determined by the physician. The higher score indicates the worse condition. Test were performed when the par. is in the on state of PD. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an on State, at Week 4 of the Maintenance Period | -1.32 Score on scale |
| Treatment Group B: 4 mg/Day | Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an on State, at Week 4 of the Maintenance Period | -3.08 Score on scale |
| Treatment Group C: 8 mg/Day | Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an on State, at Week 4 of the Maintenance Period | -3.06 Score on scale |
| Treatment Group D: 12 mg/Day | Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an on State, at Week 4 of the Maintenance Period | -2.18 Score on scale |
| Treatment Group E: 16 mg/Day | Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an on State, at Week 4 of the Maintenance Period | -2.63 Score on scale |
| Treatment Group F: 24 mg/Day | Change From Baseline in UPDRS Activities of Daily Living (ADL) Score With Participants in an on State, at Week 4 of the Maintenance Period | -3.04 Score on scale |
p-value: 0.047Mixed Models Analysis
p-value: 0.005Mixed Models Analysis
p-value: 0.172Mixed Models Analysis
p-value: 0.034Mixed Models Analysis
p-value: 0.039Mixed Models Analysis
Secondary
Change From Baseline in UPDRS ADL Score With Participants in an Off State, at Week 4 of the Maintenance Period
The UPDRS Part II is the ADL score and can range from 0 to 52 as determined by the physician. The higher score indicates the worse condition. Test was performed when the par is in the off state of PD. The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in UPDRS ADL Score With Participants in an Off State, at Week 4 of the Maintenance Period | -2.94 Score on scale |
| Treatment Group B: 4 mg/Day | Change From Baseline in UPDRS ADL Score With Participants in an Off State, at Week 4 of the Maintenance Period | -4.50 Score on scale |
| Treatment Group C: 8 mg/Day | Change From Baseline in UPDRS ADL Score With Participants in an Off State, at Week 4 of the Maintenance Period | -4.72 Score on scale |
| Treatment Group D: 12 mg/Day | Change From Baseline in UPDRS ADL Score With Participants in an Off State, at Week 4 of the Maintenance Period | -4.29 Score on scale |
| Treatment Group E: 16 mg/Day | Change From Baseline in UPDRS ADL Score With Participants in an Off State, at Week 4 of the Maintenance Period | -5.76 Score on scale |
| Treatment Group F: 24 mg/Day | Change From Baseline in UPDRS ADL Score With Participants in an Off State, at Week 4 of the Maintenance Period | -4.77 Score on scale |
p-value: 0.292Mixed Models Analysis
p-value: 0.068Mixed Models Analysis
p-value: 0.17Mixed Models Analysis
p-value: 0.003Mixed Models Analysis
p-value: 0.153Mixed Models Analysis
Secondary
Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period
The UPDRS Part I scores mentation, behavior and mood as determined by a physician and par. were tested during the on phase of PD. This component of the UPDRS is the total score for 4 items (the items 1 to 4 include intellectual impairment, thought disorder, motivation / initiative, and depression) and may have a value ranging from 0 to 16 as determined by a physician. The higher score (16) indicates the maximum score and the worse condition. All 4 items have to be present for a total score to be calculated. If one or more items are missing, the total score for the component would also be missing. BL is defined as the last non-missing assessment measured on or before the first dose date. The change from BL was calculated by subtracting the BL values from the individual post-randomization values. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline (BL) and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period | -0.24 Score on scale |
| Treatment Group B: 4 mg/Day | Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period | -0.44 Score on scale |
| Treatment Group C: 8 mg/Day | Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period | -0.33 Score on scale |
| Treatment Group D: 12 mg/Day | Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period | -0.24 Score on scale |
| Treatment Group E: 16 mg/Day | Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period | -0.47 Score on scale |
| Treatment Group F: 24 mg/Day | Change From Baseline in UPDRS Part I at Week 4 of the Maintenance Period | -0.45 Score on scale |
p-value: 0.409Mixed Models Analysis
p-value: 0.598Mixed Models Analysis
p-value: 0.992Mixed Models Analysis
p-value: 0.169Mixed Models Analysis
p-value: 0.348Mixed Models Analysis
Secondary
Percentage of Participants With a >=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period
The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. Percentage of participants meeting the criterion (LS mean on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline 'off-time', treatment, visit and treatment\*visit are included in the model.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Percentage of Participants With a >=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 72.1 percentage of participants |
| Treatment Group B: 4 mg/Day | Percentage of Participants With a >=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 70.1 percentage of participants |
| Treatment Group C: 8 mg/Day | Percentage of Participants With a >=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 80.6 percentage of participants |
| Treatment Group D: 12 mg/Day | Percentage of Participants With a >=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 73.5 percentage of participants |
| Treatment Group E: 16 mg/Day | Percentage of Participants With a >=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 83.2 percentage of participants |
| Treatment Group F: 24 mg/Day | Percentage of Participants With a >=1 Hour Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 81.4 percentage of participants |
p-value: 0.86195% CI: [0.31, 2.659]Generalized Estimating Equations model
p-value: 0.27795% CI: [0.684, 3.782]Generalized Estimating Equations model
p-value: 0.86995% CI: [0.461, 2.5]Generalized Estimating Equations model
p-value: 0.1495% CI: [0.808, 4.545]Generalized Estimating Equations model
p-value: 0.36295% CI: [0.547, 5.218]Generalized Estimating Equations model
Secondary
Percentage of Participants With a >=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period
The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values. Percentage of participants meeting the criterion (LS mean on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline 'off-time', treatment, visit and treatment\*visit are included in the model.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Percentage of Participants With a >=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 53.7 percentage of participants |
| Treatment Group B: 4 mg/Day | Percentage of Participants With a >=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 45.6 percentage of participants |
| Treatment Group C: 8 mg/Day | Percentage of Participants With a >=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 68.2 percentage of participants |
| Treatment Group D: 12 mg/Day | Percentage of Participants With a >=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 53.6 percentage of participants |
| Treatment Group E: 16 mg/Day | Percentage of Participants With a >=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 63.2 percentage of participants |
| Treatment Group F: 24 mg/Day | Percentage of Participants With a >=2 Hours Reduction in Baseline Off Time at Week 4 of the Maintenance Period | 51.3 percentage of participants |
p-value: 0.52595% CI: [0.266, 1.965]Generalized Estimating Equations model
p-value: 0.1395% CI: [0.834, 4.109]Generalized Estimating Equations model
p-value: 0.99295% CI: [0.444, 2.232]Generalized Estimating Equations model
p-value: 0.32995% CI: [0.674, 3.248]Generalized Estimating Equations model
p-value: 0.85695% CI: [0.315, 2.61]Generalized Estimating Equations model
Secondary
Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy
The percentage of participants who withdrew from the study due to lack of efficacy as defined by either the participant or the investigator is presented here. All participants with a non-missing efficacy observation at Baseline and at least one post-Baseline efficacy assessment at any time during the study were analyzed.
Time frame: From start of study treatment until end of treatment (assessed up to 18 weeks)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and at least one post-Baseline efficacy assessment at any time during the study were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group A: Placebo | Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy | 0 Percentage of participants |
| Treatment Group B: 4 mg/Day | Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy | 0 Percentage of participants |
| Treatment Group C: 8 mg/Day | Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy | 0 Percentage of participants |
| Treatment Group D: 12 mg/Day | Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy | 0 Percentage of participants |
| Treatment Group E: 16 mg/Day | Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy | 3 Percentage of participants |
| Treatment Group F: 24 mg/Day | Percentage of Participants Withdrawn From the Study Due to Lack of Efficacy | 0 Percentage of participants |
Secondary
Percent Change From Baseline in Awake Time Spent Off at Week 4 of the Maintenance Period
The off state is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia), with or without additional features such as tremor or rigidity. Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent off per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent off in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values multiplied (×) the results with 100. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Percent Change From Baseline in Awake Time Spent Off at Week 4 of the Maintenance Period | -30.44 Percentage of off time in hours |
| Treatment Group B: 4 mg/Day | Percent Change From Baseline in Awake Time Spent Off at Week 4 of the Maintenance Period | -30.47 Percentage of off time in hours |
| Treatment Group C: 8 mg/Day | Percent Change From Baseline in Awake Time Spent Off at Week 4 of the Maintenance Period | -46.65 Percentage of off time in hours |
| Treatment Group D: 12 mg/Day | Percent Change From Baseline in Awake Time Spent Off at Week 4 of the Maintenance Period | -37.26 Percentage of off time in hours |
| Treatment Group E: 16 mg/Day | Percent Change From Baseline in Awake Time Spent Off at Week 4 of the Maintenance Period | -48.36 Percentage of off time in hours |
| Treatment Group F: 24 mg/Day | Percent Change From Baseline in Awake Time Spent Off at Week 4 of the Maintenance Period | -34.37 Percentage of off time in hours |
p-value: 0.998Mixed Models Analysis
p-value: 0.017Mixed Models Analysis
p-value: 0.312Mixed Models Analysis
p-value: 0.008Mixed Models Analysis
p-value: 0.659Mixed Models Analysis
Secondary
Percent Change From Baseline in Awake Time Spent on at Week 4 of the Maintenance Period
Par. were asked to recordawake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values × 100. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Percent Change From Baseline in Awake Time Spent on at Week 4 of the Maintenance Period | 21.31 Percentage of on time in hours |
| Treatment Group B: 4 mg/Day | Percent Change From Baseline in Awake Time Spent on at Week 4 of the Maintenance Period | 15.05 Percentage of on time in hours |
| Treatment Group C: 8 mg/Day | Percent Change From Baseline in Awake Time Spent on at Week 4 of the Maintenance Period | 35.68 Percentage of on time in hours |
| Treatment Group D: 12 mg/Day | Percent Change From Baseline in Awake Time Spent on at Week 4 of the Maintenance Period | 31.28 Percentage of on time in hours |
| Treatment Group E: 16 mg/Day | Percent Change From Baseline in Awake Time Spent on at Week 4 of the Maintenance Period | 32.34 Percentage of on time in hours |
| Treatment Group F: 24 mg/Day | Percent Change From Baseline in Awake Time Spent on at Week 4 of the Maintenance Period | 32.43 Percentage of on time in hours |
p-value: 0.486Mixed Models Analysis
p-value: 0.026Mixed Models Analysis
p-value: 0.121Mixed Models Analysis
p-value: 0.081Mixed Models Analysis
p-value: 0.187Mixed Models Analysis
Secondary
Percent Change From Baseline in Awake Time Spent on Without TD at Week 4 of the Maintenance Period
Dyskinesias are involuntary twisting, turning movements caused by medication during on time in PD. TD is defined as those movements that interfere with function and cause meaningful discomfort. Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total number of awake hours spent on without TD per 24-hour period was the average across the 2 diary cards of the sum of awake hours spent on without TD in each 24-hour diary card. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL values × 100. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Percent Change From Baseline in Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 24.55 Percentage of on time in hours |
| Treatment Group B: 4 mg/Day | Percent Change From Baseline in Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 15.20 Percentage of on time in hours |
| Treatment Group C: 8 mg/Day | Percent Change From Baseline in Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 35.20 Percentage of on time in hours |
| Treatment Group D: 12 mg/Day | Percent Change From Baseline in Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 32.02 Percentage of on time in hours |
| Treatment Group E: 16 mg/Day | Percent Change From Baseline in Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 34.45 Percentage of on time in hours |
| Treatment Group F: 24 mg/Day | Percent Change From Baseline in Awake Time Spent on Without TD at Week 4 of the Maintenance Period | 29.58 Percentage of on time in hours |
p-value: 0.337Mixed Models Analysis
p-value: 0.126Mixed Models Analysis
p-value: 0.283Mixed Models Analysis
p-value: 0.148Mixed Models Analysis
p-value: 0.581Mixed Models Analysis
Secondary
Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period
Par. were asked to record awake time off, awake time on, TD during awake time on, or time asleep for all 30 minute time intervals in 24 hour diary cards for the 2 days preceding each visit of the study. The total sleep hours during the night time hours of sleep was the average across the 2 diary cards of the sum of time (hours) asleep during night time in each 24-hour diary card. BL is defined as the last non-missing assessment measured on or before the first dose date. The percent change from BL was calculated by subtracting the BL values from the Maintenance Period Week 4 values divided by BL value × 100. LS means, 95% CIs and P-values were estimated from MMRM.
Time frame: Baseline and Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period | 3.99 Percentage of total sleep time in hours |
| Treatment Group B: 4 mg/Day | Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period | 10.79 Percentage of total sleep time in hours |
| Treatment Group C: 8 mg/Day | Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period | 4.94 Percentage of total sleep time in hours |
| Treatment Group D: 12 mg/Day | Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period | 3.41 Percentage of total sleep time in hours |
| Treatment Group E: 16 mg/Day | Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period | 3.60 Percentage of total sleep time in hours |
| Treatment Group F: 24 mg/Day | Percent Change From Baseline in Total Sleep Time During the Night Time Hours of Sleep, at Week 4 of the Maintenance Period | 0.91 Percentage of total sleep time in hours |
p-value: 0.134Mixed Models Analysis
p-value: 0.768Mixed Models Analysis
p-value: 0.859Mixed Models Analysis
p-value: 0.903Mixed Models Analysis
p-value: 0.47Mixed Models Analysis
Secondary
Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period
The CGI-I scale allows the investigator to rate the participant's total improvement since the beginning of treatment (Baseline). Baseline is defined as the last non-missing assessment measured on or before the first dose date. The scale is rated from 1-7 where 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. The responder rate is defined as the percentage of participants with a score of 1 or 2. The Generalized Estimating Equations (GEE) model was used to determine CGI responder rate with treatment, visit, and treatment by visit interaction included in the model. Only scheduled visits were included.
Time frame: Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment Group A: Placebo | Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period | 35 Percentage of participants |
| Treatment Group B: 4 mg/Day | Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period | 28 Percentage of participants |
| Treatment Group C: 8 mg/Day | Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period | 39 Percentage of participants |
| Treatment Group D: 12 mg/Day | Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period | 42 Percentage of participants |
| Treatment Group E: 16 mg/Day | Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period | 46 Percentage of participants |
| Treatment Group F: 24 mg/Day | Responder Rate According to the Clinical Global Impression-global Improvement (CGI-I) Scale at Week 4 of the Maintenance Period | 56 Percentage of participants |
Secondary
Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) Off Time at Week-4 of Maintenance Period
The responder rate was defined as the percentage of par with greater than or equal to (\>=) 20 percent (%) reduction in their individual BL off time at Week 4 of the Maintenance Period. The off time is defined as the state in which the participants' symptoms include lack of mobility (bradykinesia) with or without additional features such as tremor or rigidity. BL is defined as the last non-missing assessment measured on or before the first dose date. Responder Rate (Least Squares \[LS\] means on inverse linked scale), odds ratio with 95% CI and p-value comparing against placebo were estimated by Generalized Estimating Equations (GEE) model. Baseline total awake time 'Off', treatment, visit and treatment\*visit are included in the model.
Time frame: Week 4 of the Maintenance Period (Study Week 17)
Population: ITT Population. Participants with a non-missing efficacy observation at Baseline and during the maintenance period were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Treatment Group A: Placebo | Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) Off Time at Week-4 of Maintenance Period | 65.4 percentage of participants |
| Treatment Group B: 4 mg/Day | Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) Off Time at Week-4 of Maintenance Period | 68.0 percentage of participants |
| Treatment Group C: 8 mg/Day | Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) Off Time at Week-4 of Maintenance Period | 75.4 percentage of participants |
| Treatment Group D: 12 mg/Day | Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) Off Time at Week-4 of Maintenance Period | 64.3 percentage of participants |
| Treatment Group E: 16 mg/Day | Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) Off Time at Week-4 of Maintenance Period | 77.9 percentage of participants |
| Treatment Group F: 24 mg/Day | Responder Rate Defined as the Percentage of Participants With a 20% Reduction in Baseline (BL) Off Time at Week-4 of Maintenance Period | 72.0 percentage of participants |
p-value: 0.82695% CI: [0.398, 3.166]Generalized Estimating Equations model
p-value: 0.23395% CI: [0.732, 3.593]Generalized Estimating Equations model
p-value: 0.90295% CI: [0.439, 2.065]Generalized Estimating Equations model
p-value: 0.12795% CI: [0.837, 4.158]Generalized Estimating Equations model
p-value: 0.56495% CI: [0.477, 3.888]Generalized Estimating Equations model