Clinical trial NCT01628926: A Placebo- and Ropinirole-Controlled Study for SPM 962 in Advanced Parkinson's Disease Patients
Official title: A Double-Blind, 3-Arm, Parallel Group, Placebo- and Ropinirole-Controlled Study for SPM 962 in Advanced Parkinson's Disease Patients With Concomitant Treatment of L-dopa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Parkinson's Disease
Lead sponsor: Otsuka Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2012-06-27
Enrollment: 420
Sex: ALL
Minimum age (years): 30
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: * To demonstrate the non-inferiority of SPM 962 to ropinirole in terms of efficacy in order to confirm clinical value of SPM 962.
* To demonstrate the superiority of SPM 962 to placebo in terms of efficacy.
* To investigate the tolerability and safety of SPM 962 up to 36.0 mg/day.


Eligibility criteria: Inclusion Criteria:

* Subject diagnosed as having Parkinson's disease in accordance with "Diagnostic Criteria established by the Research Committee of MHLW-specified Intractable Neurodegenerative Diseases (1995)".
* Subject is 30 and more and less than 80 years of age at the time of informed consent.
* Hoehn \& Yahr stage 2-4 (on time).
* Total UPDRS Part 3 score is over 10 at screening test (on time).
* Subject is on a stable dose of L-dopa with no change in daily dose or dosing regimen for at least 28 days prior to the initial treatment of SPM 962.
* Subject has any of the following problematic symptoms; 1) Wearing off phenomenon (including frozen gait at off time and dystonia at off time) 2) On and off phenomenon 3) Delayed-on and/or No-on phenomenon 4) Dyskinesia 5) Not well controlled with L-dopa.

Exclusion Criteria:

* Subject who has previously participated in a clinical trial of SPM962 and taken the investigational product (IP).
* Subject has psychiatric symptoms, e.g. confusion, hallucination, delusion, excitation, delirium, abnormal behavior at screening test or baseline.
* Subject whose SBP declines by at least 30 mmHg from supine to standing position based on the orthostatic hypotension assessment, or subject who develops orthostatic hypotension at baseline.
* Subject has a history of epilepsy, convulsion and other.
* Subject who has complications or a history of serious cardiac diseases or arrhythmia (eg, congestive heart failure of class 3 or 4 in the NYHA classification, second or third degree atrioventricular block, complete left bundle branch block, sick sinus syndrome, ventricular fibrillation, myocardial infarction within 12 months prior to the screening test, or a complication of angina pectoris).
* Subjects has QTc-interval \>450 msec twice at screening. Subject has a the average QTc-interval from two ECGs \>450 msec in males and \>470 msec in females at baseline.
* Subject has congenital long QT syndrome.
* Subject whose serum potassium level is \< 3.5mEq/L at the screening test.
* Subject has a total bilirubin \>= 3.0 mg/dL or AST(GOT) or ALT(GPT) greater than 2.5 times of the upper limit of the reference range (or \>= 100 IU/L) at screening test, or suffers complications of active phase of chronic hepatitis or liver cirrhosis.
* Subject has BUN \>= 30 mg/dL or serum creatinine \>= 2.0 mg/dl at screening test.
* Subject has a history of allergic reaction to topical agents such as transdermal patch.
* Subject has a history of known intolerance/hypersensitivity to ropinirole and/or adverse drug reactions that prevent subject from receiving treatment.
* Subject is pregnant or nursing or woman who plans pregnancy during the trial.
* Subject is receiving therapy with prohibited drug specified in the study protocol.
* Subject has a history of pallidotomy, thalamotomy, deep brain stimulation or fetal tissue transplant.
* Subject has dementia, including DLB and PDD (MMSE score \<= 24 at screening).
* Subject who has a complication or history of malignant neoplastic disease, or received treatment for the disease within 12 months prior to the screening test.
* Subject is unable to give consent.
* Subject who is unable to properly record information in a diary.
* Subject is participating in another trial of IPs or received other IPs within 12 weeks prior to commencement of study treatment.
* Investigator judges that subject is inappropriate as a study subject with other reasons.

Primary outcomes:
measure: Unified Parkinson's Disease Rating Score (UPDRS) Part 3 Sum Score
timeFrame: baseline, 16 weeks after dosing
Secondary outcomes:
measure: UPDRS Part 3 Sum Score
timeFrame: baseline, 8 and 10 weeks after dosing
measure: UPDRS Part 2 Sum Score
timeFrame: Baseline, 16 weeks after dosing
measure: Off Time
timeFrame: Baseline, 16 weeks after dosing
measure: Parkinson's Disease Sleep Scale-2 (PDSS-2)
timeFrame: Baseline, 16 weeks after dosing
measure: On Time
timeFrame: Baseline, 16 weeks after dosing
measure: On Time Without Dyskinesia Disturbing Daily Activities
timeFrame: Baseline, 16 weeks after dosing
measure: On Time With Dyskinesia Disturbing Daily Activities
timeFrame: Baseline, 16 weeks after dosing
measure: Effective Rate in UPDRS Part 3 Sum Score
timeFrame: Baseline, 16 weeks after dosing
measure: Effective Rate in UPDRS Part 2 Sum Score
timeFrame: Baseline, 16 weeks after dosing
measure: Effective Rate in Off Time
timeFrame: Baseline, 16 weeks after dosing
measure: Clinical Global Impression (CGI)
timeFrame: Baseline, 16 weeks after dosing
measure: Dystonia (at an Early Hour)
timeFrame: Baseline, 16 weeks after dosing
measure: Dystonia (in the Daytime)
timeFrame: Baseline, 16 weeks after dosing
Other outcomes:
Locations:
city: Chubu Region
country: Japan
city: Chugoku Region
country: Japan
city: Hokkaido Region
country: Japan
city: Kanto Region
country: Japan
city: Kinki Region
country: Japan
city: Kyushu Region
country: Japan
city: Shikoku Region
country: Japan
city: Tohoku Region
country: Japan
Study officials:
affiliation: Otsuka Pharmaceutical Co., Ltd.
name: Kyoji Imaoka, Mr
role: STUDY_DIRECTOR
References: