The SUSTAIN Study Compares the Effects of Sustained and I... | NCT03521635

NCT03521635

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Pramipexole SR	Experimental		Drug: Pramipexole SR
Pramipexole IR	Active Comparator		Drug: Pramipexole IR

Name	Type	Description	Arm Group Labels	Other Names
Pramipexole SR	Drug	Tablets	Pramipexole SR	MIRAPEX®/SIFROL

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to Week 18 in Parkinson's Disease Sleep Scale 2nd Version (PDSS-2) Total Score	Parkinson's disease Sleep Scale 2nd version (PDSS-2) consists of 15 questions about various sleep and nocturnal disturbances which are to be rated by the patients using one of five categories, from 0 (never) to 4 (very often). Patients were asked to rate the severity of each question based on their experience during the past week (7 days) from 0 (Never) to 4 (Very often, that meant 6 to 7 days a week). PDSS-2 total score ranges from 0 (no disturbance) to 60 (maximum nocturnal disturbance).	Baseline and Week 18

Secondary Outcomes

Measure	Description	Time Frame
Nocturnal Hypokinesia Questionnaire (NHQ) Score (Change From Baseline)	The Nocturnal Hypokinesia Questionnaire (NHQ) is designed to assess hypokinesia symptoms in night in Parkinson's disease (PD) patients, composed of two sections. Section 1 is assessed by PD patients with 10 one-point items evaluating "turning over in bed", "getting out of bed", "parkinsonian motor symptoms", and "others". Section 2 is assessed by spouses or caregivers who are with the patients during the night with 10 one-point items evaluating the same aspects as Section 1. The score for each section is by summing up points from the items in the respective section. Score of each of the two Sections is from 0 to 10, with a higher score indicating worse symptoms. The score was reported by section: Section 1 by patients, Section 2 by caregivers.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female patient with advanced idiopathic Parkinson's disease (PD) confirmed by at least bradykinesia and one of the following signs: resting tremor, rigidity.
Diagnosed as Parkinson's disease, with at least 2 years' PD history.
Of age ≥ 30 years at time of diagnosis.
Modified Hoehn and Yahr stage of 2 to 4 at on-time.
They must have clinically relevant sleep disturbances (i.e. Parkinson's Disease Sleep Scale 2nd version (PDSS-2) total score ≥18 at baseline).
They must feel uncomfortable at night because they were unable to turn around in bed or move due to immobility (i.e. the scoring of question 9 in PDSS-2 ≥ 2, that means frequency is at least 2 to 3 days during the past week).
They must have early morning off (i.e. the frequency of "feeling like bodily movements are poor when you wake up?" is at least 2 to 3 days during the past week).
Patient must have motor fluctuations (at least 2 cumulative hours of off-time every day during waking hours, documented on a patient diary completed for 2 consecutive days before randomization visit).
Patients must be treated with Levodopa combined with a Dopa-Decarboxylase-inhibitor (L-Dopa+) (i.e. standard and/or controlled release Levodopa/DDC inhibitor), or with a combination of L-Dopa+ and entacapone, at an optimized dose according to investigator's judgment, this dose being stable for at least 4 weeks prior to randomization visit.
Patients must not have been treated with sustained release dopaminergic drug (i.e. sustained release Levodopa/Dopa-Decarboxylase (DDC) inhibitor) after supper, or any anti-PD medication after 9pm within 4 weeks prior to randomization visit.
Patients must not have been treated with dopamine agonists within 4 weeks prior to randomization visit. A concomitant treatment with one or more of the following drugs will be allowed (at a stable dose for at least 4 weeks prior to randomization visit and the investigator does not intend to change this treatment during the treatment phase):
- Anti-parkinsonian anticholinergics;
- Selegiline, rasagiline, or other Monoamine Oxydase (MAO)-B-Inhibitor;
- Amantadine;
- Entacapone (or other Catechol-O-Methyltransferase (COMT)-Inhibitor).
Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information.
Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial.

Exclusion criteria:

Secondary parkinsonian syndromes due to drugs (e.g., metoclopramide, flunarizine), metabolic disorders (e.g., Wilson's disease), encephalitis or degenerative diseases (e.g., progressive supranuclear palsy).
Dementia, as defined by a Mini-Mental State Exam score < 24 at screening visit.
Any psychiatric disorder according to DSM-V Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria that could prevent compliance or completion of the study and/or put the patient at risk if he/she takes part in the study.
History of psychosis, except history of drug induced hallucinations (provided the investigator considers that participation to the trial would not represent a significant risk for the patient).
History of deep brain stimulation.
History of nucleus lesioning.
Clinically significant electrocardiogram (ECG) abnormalities at screening visit, according to investigator's judgement.
Clinically significant hypotension (i.e. supine systolic blood pressure < 90 mmHg) and/or symptomatic orthostatic hypotension (i.e. clinical symptoms of orthostatic hypotension associated with a decline ≥ 20 mmHg in systolic blood pressure and a decline ≥ 10 mmHg in diastolic blood pressure, at 1 minute after standing compared with the previous supine systolic and diastolic blood pressure obtained after 5 minutes of quiet rest) at screening or randomization visit.
Major surgery (major according to the investigator's assessment) performed within 12 weeks prior to randomization or planned within 12 months after screening, e.g. hip replacement.
Any other clinically significant disease, whether treated or not, that could put the patient at risk or could prevent compliance or completion of the study.
Serious Sleep Apnea Hypopnea Syndrome (i.e. the scoring of question 15 in Parkinson's Disease Sleep Scale 2nd version (PDSS-2)≥ 3, that means frequency is at least 4 to 5 days during the past week )
Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or in situ carcinoma of uterine cervix.
Serum levels of Aspartate Aminotransferase (AST)(SGOT), Alanine Aminotransferase (ALT)(SGPT), alkaline phosphatases or total bilirubin >2 ULN (on screening lab test).
Patients with a creatinine clearance < 50 mL/min (estimated by the local lab / the investigator using the Modification of Diet in Renal Disease (MDRD, please refer to Appendix 10.1), and calculated on screening lab test).
Any hypnotic medication within 4 weeks prior to the randomization visit (i.e. diazepam, clonazepam, estazolam, alprazolam, zolpidem, etc.).
Any medication (including intra-muscular formulations) with central dopaminergic antagonist activity within 4 weeks prior to the randomization visit (i.e. typical neuroleptics, atypical antipsychotics, reserpine, methyldopa, centrally-active antiemetics, etc.).
Any of the following drugs within 4 weeks prior to randomization visit: methylphenidate, cinnarizine, amphetamines.
Flunarizine within 3 months prior to randomization visit.
Known hypersensitivity to Pramipexole or its excipients.
Patients who must or wish to continue the intake of restricted medications or any drug considered likely to interfere with the safe conduct of the trial.
Previous enrolment in this trial.
Currently enrolled in another investigational device or drug trial, or less than 30 days since ending another investigational device or drug trial(s), or receiving other investigational treatment(s).
Chronic alcohol or drug abuse or any condition that, in the investigator's opinion, makes them an unreliable trial patient or unlikely to complete the trial.
Women who are pregnant, nursing, or who plan to become pregnant in the trial.

Contacts/Locations Module

Facility	Status	City	State	ZIP	Country	Contacts
Peking Union Medical College Hospital		Beijing		100032	China
Beijing Hospital

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 18, 2018	Dec 18, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Treated set (TS) was defined as all patients who were dispensed study medication and were documented to have at least one dose of investigational treatment.

Arm/Group Information

ID	Title	Description
BG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
BG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00049 BG00149 BG00298

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00061.1± 10.80 BG00160.9± 8.83 BG00261.0± 9.82

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00021 BG00118 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Parkinson's disease Sleep Scale 2nd version (PDSS-2) total score

Patients were asked to rate the severity of each question based on their experience during the past week (7 days) from 0 (Never) to 4 (Very often, that meant 6 to 7 days a week). PDSS-2 total score ranges from 0 (no disturbance) to 60 (maximum nocturnal disturbance).

Mean

Standard Deviation

Score on scale

Title

Denominators

Categories

Title	Measurements
	BG00027.8± 6.45 BG001

Parkinson's disease Questionnaire (PDQ) -8 score

The PDQ-8 is a self-reported questionnaire consisting of 8 questions regarding the subject's disease symptoms, each item ranging from 0 to 4, and the responses consist of 0=Never, 1=Occasionally, 2=Sometimes, 3=Often, and 4=Always or cannot do at all, total score ranging from 0 (never have problems/issues) to 32 (always have problems or cannot do at all).

Mean

Standard Deviation

Score on a scale

Title

Denominators

Categories

Title	Measurements
	BG00011.3± 4.83 BG001

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

Change From Baseline to Week 18 in Parkinson's Disease Sleep Scale 2nd Version (PDSS-2) Total Score

Parkinson's disease Sleep Scale 2nd version (PDSS-2) consists of 15 questions about various sleep and nocturnal disturbances which are to be rated by the patients using one of five categories, from 0 (never) to 4 (very often). Patients were asked to rate the severity of each question based on their experience during the past week (7 days) from 0 (Never) to 4 (Very often, that meant 6 to 7 days a week). PDSS-2 total score ranges from 0 (no disturbance) to 60 (maximum nocturnal disturbance).

Full analysis set (FAS) was defined as all patients who were randomised to treatment and received at least one dose of study drug and providing a baseline and at least one PDSS-2 total score measurement in maintenance period.

Posted

Mean

Standard Error

Score on a scale

Baseline and Week 18

ID	Title	Description
OG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
OG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.

Units	Counts
Participants	OG00045 OG00143

Title

Denominators

Categories

Title	Measurements
	OG000-13.7± 1.16 OG001-14.4± 1.20

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Mean changes from baseline of PDSS-2 score were analysed using a restricted maximum likelihood (REML) - based repeated measures approach. Analyses included the fixed, categorical effects of treatment, visit in the maintenance period, and treatment-by-visit interaction, and the continuous, fixed covariates of baseline and baseline-by-visit interaction.	REML-based repeated measures approach	Restricted maximum likelihood (REML) - based repeated measures approach was applied.	0.688		Adjusted mean difference	0.7	Standard Error of the Mean	1.68	2-Sided	95	-2.7	4.0			Mean difference was calculated as Pramipexole Sustained Release minus Pramipexole immediate Release

Secondary

Nocturnal Hypokinesia Questionnaire (NHQ) Score (Change From Baseline)

The Nocturnal Hypokinesia Questionnaire (NHQ) is designed to assess hypokinesia symptoms in night in Parkinson's disease (PD) patients, composed of two sections. Section 1 is assessed by PD patients with 10 one-point items evaluating "turning over in bed", "getting out of bed", "parkinsonian motor symptoms", and "others". Section 2 is assessed by spouses or caregivers who are with the patients during the night with 10 one-point items evaluating the same aspects as Section 1. The score for each section is by summing up points from the items in the respective section. Score of each of the two Sections is from 0 to 10, with a higher score indicating worse symptoms. The score was reported by section: Section 1 by patients, Section 2 by caregivers.

Posted

Mean

Standard Error

Score on a scale

Baseline and Week 18

ID	Title	Description
OG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
OG001

Secondary

Scale for Outcomes in Parkinson's Disease (SCOPA)-Sleep Score (Change From Baseline)

SCOPA-Sleep score is composed of three parts: a night-time scale (5 item scale with 4 Response Options (0-not at all to 3-very much) addressing night time disturbances. Total night-time scale score runs from 0 to 15, with a higher score indicating more severe problems, a single-item about perceived quality of nocturnal sleep (7-point scale ranging from slept very well to slept very badly.), and a daytime sleepiness scale (6 items with 4 Response options, from 0 (never) to 3 (often), and a maximum total score of 18.).

Posted

Mean

Standard Error

Score on a scale

Baseline and Week 18

ID	Title	Description
OG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
OG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.

Secondary

Early Morning Off (EMO) Score (Change From Baseline)

The EMO is measured by the question of "do you feel like your bodily movements are poor when you wake up?" Patients answered this question according to the frequency during the previous one week by scoring from 0 ("never") to 4 ("very often" or "6 to 7 days a week").

Posted

Mean

Standard Error

Score on a scale

Baseline and Week 18

ID	Title	Description
OG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
OG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.

Secondary

Responder Rate for Parkinson's Disease Sleep Scale 2nd Version (PDSS-2) Total Score<18

Parkinson's disease Sleep Scale 2nd version (PDSS-2) consists of 15 questions about various sleep and nocturnal disturbances which are to be rated by the patients using one of five categories, from 0 (never) to 4 (very often) based on their experience during the past week. PDSS-2 total score ranges from 0 (no disturbance) to 60 (maximum nocturnal disturbance). The PDSS-2 total score less < 18 were compared between groups.

Posted

Number

95% Confidence Interval

Percentage of participants

At Week 18

ID	Title	Description
OG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
OG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.

Secondary

Responder Rate for Early Morning Off (EMO) Score

The responder of EMO is the patient with an improvement of at least 1 comparing to his/her baseline condition. The EMO is measured by the question of "do you feel like your bodily movements are poor when you wake up?" Patients answered this question according to the frequency during the previous one week by scoring from 0 ("never") to 4 ("very often" or "6 to 7 days a week").

Posted

Number

95% Confidence Interval

Percentage of participants

At Week 18

ID	Title	Description
OG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
OG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.

Secondary

The Parkinson's Disease Questionnaire (PDQ)-8 Score (Change From Baseline)

The PDQ-8 is a self-reported questionnaire consisting of 8 questions regarding the subject's disease symptoms. The total score summed up the items together and transformed onto a score from 0 (never have problems/issues) to 100 (always have problems or cannot do at all).

Posted

Mean

Standard Error

Score on a scale

Baseline and Week 18

ID	Title	Description
OG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
OG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.

Secondary

Responder Rate for Clinical Global Impression of Improvement (CGI-I)

The responder of CGI-I is the patient rated of any improvement (1 = Very much better, 2 = Much better, or 3 = A little better). The CGI-I was rated (from 1: very much improved, to 7: very much worse) by the same evaluator to assess the overall status of Parkinson's disease.

Posted

Number

95% Confidence Interval

Percentage of participants

At Week 18

ID	Title	Description
OG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
OG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.

Secondary

Responder Rate for Patient Global Impression of Improvement (PGI-I)

The responder of PGI-I is the patient rated of any improvement (1 = Very much better, 2 = Much better, or 3 = A little better). The PGI-I scale is a patient-rated instrument (from 1: very much better, to 7: very much worse) which was used to measure the improvement of the patient's Parkinson disease symptoms throughout the study.

Posted

Number

95% Confidence Interval

Percentage of participants

At Week 18

ID	Title	Description
OG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
OG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.

Secondary

Epworth Sleepiness Scale (ESS) Score (Change From Baseline)

The ESS is a patient-rated scale about how likely one is to fall asleep during situations of passive and inconsequential to active. The total score ranges from 0-24 where higher values indicate greater daytime sleepiness.

Posted

Mean

Standard Error

Score on a scale

Baseline and Week 18

ID	Title	Description
OG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.
OG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pramipexole Sustained Release	Tablets of Pramipexole sustained release (SR) with unit strength of 0.375 milligram (mg) and 0.75 mg were administered orally once daily at 7-9 pm before bedtime to achieve daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg for a treatment period of 18 weeks. The dose of Pramipexole SR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.	0	49	0	49	4	49
EG001	Pramipexole Immediate Release	Tablets of Pramipexole immediate release (IR) with unit strength of 0.25 milligram (mg) and 1.0 mg were administered in equally divided doses three times per day to achieve a total daily dose of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg, or 4.5 mg, the third dose at 7-9 pm before bedtime for a treatment period of 18 weeks. The dose of Pramipexole IR was titrated to an optimised level, to achieve a maximum therapeutic effect without intolerable side effects.	0	49	1	49	7	49

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Mechanical ileus	Gastrointestinal disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected49 at risk EG0011 affected49 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected49 at risk EG0011 affected49 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 22.1	Systematic Assessment	EG0000 affected49 at risk EG0011 affected49 at risk
Femoral neck fracture	Injury, poisoning and procedural complications	MedDRA 22.1	Systematic Assessment	EG0000 affected49 at risk EG0011 affected49 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dizziness	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0003 affected49 at risk EG0013 affected49 at risk
Dyskinesia	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected49 at risk EG0013 affected49 at risk
Somnolence	Nervous system disorders	MedDRA 22.1	Systematic Assessment	EG0001 affected49 at risk EG0013 affected49 at risk

According to the study results, the decision was made to stop transitioning to Stage II. Therefore, only results of Stage I were reported.

Certain Agreements

First MCP Posted Date

ID	Term
D010300	Parkinson Disease

Ancestor Terms

ID	Term
D020734	Parkinsonian Disorders
D001480	Basal Ganglia Diseases
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D009069	Movement Disorders
D000080874	Synucleinopathies
D019636	Neurodegenerative Diseases