Rotigotine Versus Placebo As Double Blind Study To Evalua... | NCT01646268

Status Module

Label	Type	Description	Intervention Names
Rotigotine	Experimental	Rotigotine, daily doses, treatment group	Drug: Rotigotine
Placebo	Placebo Comparator	Placebo, daily doses, placebo group	Drug: Placebo Patch

Name	Type	Description	Arm Group Labels	Other Names
Rotigotine	Drug	Transdermal Patch Content: 2 mg /24 h (10 cm^2), 4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2) For early-stage Parkinson's disease, receive Rotigotine patches in escalating weekly dose (starting with daily doses 2 mg/24 h to 8 mg/24 h) for a maximum 4-week Titration Period, then 24 week maintenance period

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in the Sum of the Score From the Activities of Daily Living (ADL) Scale and Motor Examination in the Unified Parkinson's Disease Rating Scale (UPDRS) (Parts II+III, a UPDRS Subtotal) From Baseline to the End of Double-blind Maintenance Period	The UPDRS assessments (Parts II+III) will be performed at every visit. For the assessment of the subject's disability, Part II of the UPDRS will be used. Data will be gathered pertaining to the subject's disease state in the "on" state. Subjects will respond to questions about their general state in the week prior to their scheduled visit in conjunction with any observations made by the investigator (or designee). For the assessment of the subject's motor function, Part III of the UPDRS will be used and the assessments will be done while the subject is in the "on" state. The UPDRS Part II (Activities of Daily Living) consists of 13 items scored between 0 and 4. The UPDRS Part III (motor subscale) consists of 27 items and sub items scored between 0 and 4. The sum score is calculated as sum of these 27 individual scores. The sum score ranges from 0 to 160, higher scores denote greater disability.	From Baseline (Week 0) to end of Maintenance Period (up to Week 24)

Secondary Outcomes

Measure	Description	Time Frame
Response to Therapy, Defined as ≥20 % Decrease in the Sum of Scores From Activities of Daily Living (ADL) & Motor Examination in Unified Parkinson's Disease Rating Scale (UPDRS Parts II+III, a UPDRS Subtotal) From Baseline to End of Maintenance Period	The UPDRS assessments (Parts II+III) will be performed at every visit. For the assessment of the subject's disability, Part II of the UPDRS will be used. Data will be gathered pertaining to the subject's disease state in the "on" state. Subjects will respond to questions about their general state in the week prior to their scheduled visit in conjunction with any observations made by the investigator (or designee). For the assessment of the subject's motor function, Part III of the UPDRS will be used and the assessments will be done while the subject is in the "on" state. The UPDRS Part II (Activities of Daily Living) consists of 13 items scored between 0 and 4. The UPDRS Part III (motor subscale) consists of 27 items and sub items scored between 0 and 4. The sum score is calculated as sum of these 27 individual scores. A higher score denotes greater disability.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

An Independent Ethics Committee (IEC)-approved written informed consent is signed and dated by the subject or by the legal representative
Subject/legal representative is considered reliable and capable of adhering to the protocol, visit schedule or study medication intake according to the judgment of the investigator
Subject has Idiopathic Parkinson's Disease of ≤5 years' duration, defined by the cardinal sign, Bradykinesia, plus the presence of at least 1 of the following: resting tremor, rigidity, or impairment of postural reflexes, and without any other known or suspected cause of Parkinsonism
Subject is Hoehn & Yahr stage ≤3
Subject is male or female aged ≥30 years at Screening (Visit 1)
Subject has a Mini Mental State Examination (MMSE) score of ≥25
Subject has a Unified Parkinson's Disease Rating Scale (UPDRS) motor score (Part III) of ≥10 at Baseline (Visit 2)
If the subject is receiving an Anticholinergic agent (eg, Benztropine, Trihexyphenidyl, Parsitan, Procyclidine, Biperiden), a monoamine oxidase (MAO)-B inhibitor (eg, Selegiline), an N-methyl-d-aspartate (NMDA) antagonist (eg, Amantadine), he/she must have been on a stable dose for at least 28 days prior to Baseline (Visit 2) and be maintained on that dose for the duration of the study

Exclusion Criteria:

Subject has previously participated in this study or subject has previously received the study medication under investigation in this study
Subject is participating in another study of an investigational drug or has done so within 28 days prior to the Baseline Visit (Visit 2)
Subject has a history of significant skin hypersensitivity to adhesive or other transdermal preparations or recent unresolved contact Dermatitis
Subject has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has suicidal ideation in the past 6 months as indicated by a positive response ("Yes") to either Question 4 or Question 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening (Visit 1)
Subject has atypical Parkinson's syndrome(s) due to drugs (eg, Metoclopramide, Flunarizine), metabolic neurogenetic disorders (eg, Wilson's Disease), Encephalitis, Cerebrovascular Disease, or Degenerative Disease (eg, progressive Supranuclear Palsy)
Subject has a history of Pallidotomy, Thalamotomy, deep brain stimulation, or fetal tissue transplant
Subject has dementia, active psychosis or hallucinations, or severe depression
Subject is receiving therapy with a dopamine agonist either concurrently or has done so within 28 days prior to the Baseline Visit (Visit 2)
Subject is receiving therapy with L dopa/carbidopa and/or L-dopa/benserazide within 28 days of Baseline (Visit 2) or has received L-dopa/carbidopa and/or L-dopa/benserazide for more than 6 months since diagnosis
Subject is receiving therapy with 1 of the following drugs either concurrently or within 28 days prior to Baseline (Visit 2): Alpha-methyl dopa, Metoclopramide, Reserpine, Neuroleptics (except specific atypical neuroleptics: Olanzapine, Ziprasidone, Aripiprazole, Clozapine, Quetiapine), MAO-A inhibitors, Methylphenidate, or Amphetamine
Subject is currently receiving central nervous system (CNS) active therapy (eg, sedatives, hypnotics, antidepressants, anxiolytics), unless the dose has been stable for at least 28 days prior to Baseline Visit (Visit 2) and is likely to remain stable for the duration of the study
Subject has a current diagnosis of Epilepsy, has a history of seizures as an adult, has a history of stroke, or has had a transient ischemic attack within 1 year prior to Screening (Visit 1)
Subject has clinically relevant hepatic dysfunction (as defined as a total bilirubin >2.0 mg/dL or alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) greater than 2 times the upper limit of the reference range)
Subject has clinically relevant renal dysfunction (serum creatinine >2.0 mg/dL [>178 umol/L])
Subject has clinically relevant cardiac dysfunction (any cardiac disorder which in the opinion of the investigator would put the subject at risk of clinically relevant arrhythmia) and/or myocardial infarction within the last 12 months
Subject has a QT interval corrected for heart rate according to Bazett's formula (QTcB) of ≥500 ms at Screening (Visit 1)
Subject has a history of only symptomatic (not asymptomatic) orthostatic hypotension with a decrease of systolic blood pressure (SBP) from supine to standing position of ≥20 mmHg or of ≥10 mmHg in diastolic blood pressure (DBP) after 1 or 3 minutes within 28 days prior to the Baseline Visit (Visit 2), or SBP less than 105 mmHg at study entry
Subject has evidence of an impulse control disorder (ICD) at Screening (Visit 1)
Subject has a history of known intolerance/hypersensitivity to the following Antiemetics; Domperidone, Trimethobenzamide, Ondansetron, Tropisetron, Granisetron, and Glycopyrrolate
Subject has a history of chronic alcohol or drug abuse within the last 5 years
Subject is pregnant or nursing, or is of childbearing potential but (i) not surgically sterile or (ii) not using adequate birth control methods (including at least a double barrier method) or (iii) not sexually abstinent or (iv) not at least 2 years post-menopausal
Subject has any other clinically relevant medical condition, psychiatric condition, or laboratory abnormality, which would in the judgment of the investigator, interfere with the subject's ability to participate in the study

Name	Affiliation	Role
UCB Clinical Trial Call Center	1 877 822 9493	Study Director

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Rotigotine	Rotigotine, daily doses, treatment group Rotigotine: Transdermal Patch Content: 2 mg /24 h (10 cm^2), 4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2) For early-stage Parkinson's disease, receive Rotigotine patches in escalating weekly dose (starting with daily doses 2 mg/24 h to 8 mg/24 h) for a maximum 4-week Titration Period, then 24 week maintenance period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

ID	Title	Description
BG000	Rotigotine	Rotigotine, daily doses, treatment group Rotigotine: Transdermal Patch Content: 2 mg /24 h (10 cm^2), 4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2) For early-stage Parkinson's disease, receive Rotigotine patches in escalating weekly dose (starting with daily doses 2 mg/24 h to 8 mg/24 h) for a maximum 4-week Titration Period, then 24 week maintenance period.
BG001	Placebo	Placebo, daily doses, placebo group Placebo Patch: Transdermal Patch Size: 10 cm^2, 20 cm^2, 30 cm^2, 40 cm^2 Subjects randomized to placebo will receive matching placebo patches.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000124 BG001123 BG002247

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 in the Sum of the Score From the Activities of Daily Living (ADL) Scale and Motor Examination in the Unified Parkinson's Disease Rating Scale (UPDRS) (Parts II+III, a UPDRS Subtotal) From Baseline to the End of Double-blind Maintenance Period

The UPDRS assessments (Parts II+III) will be performed at every visit.

For the assessment of the subject's disability, Part II of the UPDRS will be used. Data will be gathered pertaining to the subject's disease state in the "on" state. Subjects will respond to questions about their general state in the week prior to their scheduled visit in conjunction with any observations made by the investigator (or designee). For the assessment of the subject's motor function, Part III of the UPDRS will be used and the assessments will be done while the subject is in the "on" state.

The UPDRS Part II (Activities of Daily Living) consists of 13 items scored between 0 and 4. The UPDRS Part III (motor subscale) consists of 27 items and sub items scored between 0 and 4. The sum score is calculated as sum of these 27 individual scores. The sum score ranges from 0 to 160, higher scores denote greater disability.

This analysis consists of the Full Analysis Set [Last Observation Carried Forward], which includes all subjects who are randomized, receive at least 1 dose of study medication, and have a Baseline efficacy measurement and at least 1 post-Baseline efficacy measurement.

Posted

Mean

Standard Deviation

units on a scale

From Baseline (Week 0) to end of Maintenance Period (up to Week 24)

ID	Title	Description
OG000	Rotigotine	Rotigotine, daily doses, treatment group Rotigotine: Transdermal Patch Content: 2 mg /24 h (10 cm^2), 4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2) For early-stage Parkinson's disease, receive Rotigotine patches in escalating weekly dose (starting with daily doses 2 mg/24 h to 8 mg/24 h) for a maximum 4-week Titration Period, then 24 week maintenance period.
OG001	Placebo	Placebo, daily doses, placebo group Placebo Patch: Transdermal Patch Size: 10 cm^2, 20 cm^2, 30 cm^2, 40 cm^2 Subjects randomized to placebo will receive matching placebo patches.

Units	Counts
Participants	OG000123 OG001121

Title

Denominators

Categories

Title	Measurements
	OG000-4.9± 9.9 OG001-0.2± 9.9

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	The null hypothesis (H0) is that there is no difference in the change in the sum of the score from the ADL and motor examination in the UPDRS (Parts II+II) between the active treatment and the placebo groups (i.e., the change from Baseline in the sum of the score from the ADL and motor examination in the UPDRS (Parts II+III) is the same for both groups).	ANCOVA		<0.0001		LS Means	-4.82	Standard Error of the Mean	1.20	2-Sided	95	-7.18	-2.45			Value describes the difference value of the mean change from baseline between Rotigotine and Placebo groups. The Value for this outcome was -4.6.	No

Secondary

Response to Therapy, Defined as ≥20 % Decrease in the Sum of Scores From Activities of Daily Living (ADL) & Motor Examination in Unified Parkinson's Disease Rating Scale (UPDRS Parts II+III, a UPDRS Subtotal) From Baseline to End of Maintenance Period

The UPDRS assessments (Parts II+III) will be performed at every visit. For the assessment of the subject's disability, Part II of the UPDRS will be used. Data will be gathered pertaining to the subject's disease state in the "on" state. Subjects will respond to questions about their general state in the week prior to their scheduled visit in conjunction with any observations made by the investigator (or designee). For the assessment of the subject's motor function, Part III of the UPDRS will be used and the assessments will be done while the subject is in the "on" state.

Posted

Number

percentage of responders

From Baseline (Week 0) to end of Maintenance Period (up to Week 24)

ID	Title	Description
OG000	Rotigotine	Rotigotine, daily doses, treatment group Rotigotine: Transdermal Patch Content: 2 mg /24 h (10 cm^2), 4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2) For early-stage Parkinson's disease, receive Rotigotine patches in escalating weekly dose (starting with daily doses 2 mg/24 h to 8 mg/24 h) for a maximum 4-week Titration Period, then 24 week maintenance period.

Secondary

Change in Unified Parkinson's Disease Rating Scale [UPDRS Part II (ADL)] From Baseline to the End of the Double-blind Maintenance Period

The UPDRS assessments (Parts II+III) will be performed at every visit.

For the assessment of the subject's disability, Part II of the UPDRS will be used. Data will be gathered pertaining to the subject's disease state in the "on" state. Subjects will respond to questions about their general state in the week prior to their scheduled visit in conjunction with any observations made by the investigator (or designee). The UPDRS Part II (Activities of Daily Living) consists of 13 items scored between 0 and 4. The sum score ranges from 0 to 52, higher scores denote greater disability.

Posted

Mean

Standard Deviation

units on a scale

From Baseline (Week 0) to end of Maintenance Period (up to Week 24)

ID	Title	Description
OG000	Rotigotine	Rotigotine, daily doses, treatment group Rotigotine: Transdermal Patch Content: 2 mg /24 h (10 cm^2), 4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2) For early-stage Parkinson's disease, receive Rotigotine patches in escalating weekly dose (starting with daily doses 2 mg/24 h to 8 mg/24 h) for a maximum 4-week Titration Period, then 24 week maintenance period.
OG001	Placebo

Secondary

Change in Unified Parkinson's Disease Rating Scale [UPDRS Part III (Motor Examination)] From Baseline to the End of the Double-blind Maintenance Period

The UPDRS assessments (Parts II+III) will be performed at every visit.

For the assessment of the subject's motor function, Part III of the UPDRS will be used and the assessments will be done while the subject is in the "on" state.

The UPDRS Part III (motor subscale) consists of 27 items and sub items scored between 0 and 4. The sum score ranges from 0 to 108, higher scores denote greater disability.

Posted

Mean

Standard Deviation

units on a scale

From Baseline (Week 0) to end of Maintenance Period (up to Week 24)

ID	Title	Description
OG000	Rotigotine	Rotigotine, daily doses, treatment group Rotigotine: Transdermal Patch Content: 2 mg /24 h (10 cm^2), 4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2) For early-stage Parkinson's disease, receive Rotigotine patches in escalating weekly dose (starting with daily doses 2 mg/24 h to 8 mg/24 h) for a maximum 4-week Titration Period, then 24 week maintenance period.
OG001	Placebo	Placebo, daily doses, placebo group Placebo Patch: Transdermal Patch Size: 10 cm^2, 20 cm^2, 30 cm^2, 40 cm^2 Subjects randomized to placebo will receive matching placebo patches.

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	Rotigotine	Rotigotine, daily doses, treatment group Rotigotine: Transdermal Patch Content: 2 mg /24 h (10 cm^2), 4 mg /24 h (20 cm^2), 6 mg /24 h (30 cm^2), 8 mg /24 h (40 cm^2) For early-stage Parkinson's disease, receive Rotigotine patches in escalating weekly dose (starting with daily doses 2 mg/24 h to 8 mg/24 h) for a maximum 4-week Titration Period, then 24 week maintenance period.			6	124	35	124
EG001	Placebo	Placebo, daily doses, placebo group Placebo Patch: Transdermal Patch Size: 10 cm^2, 20 cm^2, 30 cm^2, 40 cm^2 Subjects randomized to placebo will receive matching placebo patches.			1	123	18	123

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Coronary artery disease	Cardiac disorders	MedDRA 16.1	Non-systematic Assessment	EG0000 events0 affected124 at risk EG0011 events1 affected123 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected123 at risk
Myocardial bridging	Congenital, familial and genetic disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected123 at risk
Gastric polyps	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected123 at risk
Large intestine polyp	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected123 at risk
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected123 at risk
Parathyroid tumour benign	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.1	Non-systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected123 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 16.1	Non-systematic Assessment	EG0001 events1 affected124 at risk EG0010 events0 affected123 at risk

Facility	Status	City	State	ZIP	Country	Contacts
001		Beijing			China
002

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

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG00016 events11 affected124 at risk EG0014 events4 affected123 at risk
Vomiting	Gastrointestinal disorders	MedDRA 16.1	Non-systematic Assessment	EG0009 events7 affected124 at risk EG0012 events2 affected123 at risk
Somnolence	Nervous system disorders	MedDRA 16.1	Non-systematic Assessment	EG00010 events10 affected124 at risk EG0014 events4 affected123 at risk
Dizziness	Nervous system disorders	MedDRA 16.1	Non-systematic Assessment	EG00013 events10 affected124 at risk EG0019 events7 affected123 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA 16.1	Non-systematic Assessment	EG00011 events8 affected124 at risk EG0012 events2 affected123 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 16.1	Non-systematic Assessment	EG00012 events10 affected124 at risk EG0015 events5 affected123 at risk