A Dose-finding Study for SPM 962 in Advanced Parkinson's Disease Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01628848
First received: June 24, 2012
Last updated: February 3, 2014
Last verified: February 2014
  Purpose

The primary objective of this study is to investigate efficacy and safety of SPM 962 in advanced Parkinson's Disease (PD) patients in a multi-center, placebo-controlled study following once-daily multiple transdermal doses of SPM 962 within a range of 4.5 to 36.0 mg (12 weeks of dose titration/maintenance period). Recommended maintenance dose range is also to be investigated with distribution of the maintenance dose and accumulated response rate of efficacy.


Condition Intervention Phase
Parkinson's Disease
Drug: SPM 962
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Placebo-controlled Dose-finding Study for SPM 962 in Advanced Parkinson's Disease Patients With Concomitant Treatment of L-dopa

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Co., Ltd.:

Primary Outcome Measures:
  • Unified Parkinson's Disease Rating Scale (UPDRS) Part 3 Sum Score [ Time Frame: baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]

    Mean change (LOCF) from baseline in UPDRS Part 3 sum score at 12 weeks after dosing.

    UPDRS is a scale for monitoring Parkinson's Disease-related disability and impairment. The UPDRS consists of the following four sub-scales. Part 1: Mentation, Part 2: Activities of Daily Living, Part 3: Motor, Part 4: Complications. Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.



Secondary Outcome Measures:
  • UPDRS Part 2 Sum Score (Average Score of on State and Off State) [ Time Frame: baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]

    Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average scores of on state and off state) at 12 weeks after dosing.

    Mean change (LOCF) from baseline in UPDRS Part 2 sum score (average score of on state and off state) at 12 weeks after dosing.

    UPDRS sub-scale Part 2 assesses 13 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.


  • Off Time [ Time Frame: baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]
    Mean change (LOCF) from baseline in off time at 12 weeks after dosing.

  • Effective Rate in UPDRS Part 3 Sum Score [ Time Frame: Baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]
    Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in UPDRS Part 3 sum score at 12 weeks after dosing.

  • UPDRS Part 1 Sum Score [ Time Frame: Baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]

    Mean change (LOCF) from baseline in UPDRS Part 1 sum score at 12 weeks after dosing.

    UPDRS sub-scale Part 1 assesses 4 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.


  • Effective Rate in Off Time [ Time Frame: Baseline, 12 weeks after dosing. ] [ Designated as safety issue: No ]
    Effective rate (percentage of subjects with 20% or 30% decrease) (LOCF) in off time at 12 weeks after dosing.

  • UPDRS Part 2 Sum Score (on State) [ Time Frame: Baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]

    Mean change (LOCF) from baseline in UPDRS Part 2 sum score (on state) at 12 weeks after dosing.

    UPDRS sub-scale Part 2 assesses 13 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.


  • UPDRS Part 2 Sum Score (Off State) [ Time Frame: Baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]

    Mean change (LOCF) from baseline in UPDRS Part 2 sum score (off state) at 12 weeks after dosing.

    UPDRS sub-scale Part 2 assesses 13 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.


  • UPDRS Part 4 Sum Score [ Time Frame: Baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]

    Mean change (LOCF) from baseline in UPDRS Part 4 sum score at 12 weeks after dosing.

    UPDRS sub-scale Part 4 assesses 11 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.


  • Total of UPDRS Part 2 Sum Score (Average Score of on State and Off State) and UPDRS Part 3 Sum Score [ Time Frame: Baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]

    Mean change (LOCF) from baseline in total of UPDRS Part 2 sum score (average score of on state and off state), and UPDRS Part 3 sum score at 12 weeks after dosing.

    UPDRS sub-scale Part 2 assesses 13 items and Part 3 assesses 14 items. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.


  • Total of UPDRS Part 1 Sum Score, UPDRS Part 2 Sum Score (Average Score of on State and Off State), UPDRS Part 3 Sum Score, and UPDRS Part 4 Sum Score. [ Time Frame: Baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]

    Mean change (LOCF) from baseline in total of UPDRS Part 1 sum score, UPDRS Part 2 sum score (average score of on state and off state), UPDRS Part 3 sum score, and UPDRS Part 4 sum score at 12 weeks after dosing.

    UPDRS sub-scale Part 1, 2, 3, and 4 assess 4, 13, 14, and 11 items respectively. Each item is scored from 0 (normal) to 4 (severe). The sum score serves as the sub-scale score. A higher score indicates a greater severity of symptoms. Thus a decrease in the scores means improvement.


  • The Modified Hoehn & Yahr Severity of Illness [ Time Frame: Baseline, 12 weeks after dosing ] [ Designated as safety issue: No ]

    Mean change (LOCF) from baseline in the Modified Hoehn & Yahr Severity of Illness at 12 weeks after dosing.

    The Modified Hoehn & Yahr criteria are measured on the following 8-point scale for staging: 0, No signs of disease; 1, Unilateral disease; 1.5, Unilateral plus axial involvement; 2, Bilateral disease without impairment of balance; 2.5, Mild bilateral disease with recovery on pull test; 3, Mild to moderate bilateral disease, some postural instability, physically independent 4, Severe disability, still able to walk or stand unassisted; and 5, Wheelchair bound or bedridden unless aided.



Enrollment: 174
Study Start Date: August 2006
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SPM 962
SPM 962 transdermal patch
Drug: SPM 962
SPM 962 transdermal patch once a daily up to 36.0 mg/day
Placebo Comparator: Placebo
Placebo transdermal patch
Drug: Placebo
Placebo transdermal patch

  Eligibility

Ages Eligible for Study:   30 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 2) On and off phenomenon 3) Delayed-on and/or No-on phenomenon 4) Not well controlled with L-dopa due to adverse effect 5) Weakening of L-dopa efficacy.

Exclusion Criteria:

  • Subject has previously participated in a trial with SPM 962.
  • Subject is on other dopamine agonist treatment within 28 days prior to the initial treatment.
  • Subject has psychiatric symptoms, e.g. confusion, hallucination, delusion, excitation, delirium, abnormal behavior at screening test or baseline.
  • Subject has orthostatic hypotension.
  • Subject has a history of epilepsy, convulsion and other.
  • Subject has a complication of serious cardiac disorder or has the history.
  • Subject has arrhythmia and treated with class 1a antiarrhythmic drugs (e.g. quinidine, procainamide etc.) or class 3 antiarrhythmic drugs (e.g. amiodarone, sotalol etc.).
  • At screening and baseline, subject develops serious ECG abnormality. 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 has hypokalaemia.
  • 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.
  • Subject has BUN >= 25 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 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.
  • Subject is unable to give consent.
  • Subject is participating in another trial of an investigational drug or done so within 24 weeks prior to the initial treatment.
  • Investigator judges that subject is inappropriate as a study subject with other reasons.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01628848

Locations
Japan
Chubu Region, Japan
Hokkaido Region, Japan
Kanto Region, Japan
Kinki Region, Japan
Kyushu Region, Japan
Shikoku Region, Japan
Tohoku Region, Japan
Sponsors and Collaborators
Otsuka Pharmaceutical Co., Ltd.
Investigators
Study Director: Kyoji Imaoka, Mr Otsuka Pharmaceutical Co., Ltd.
  More Information

No publications provided

Responsible Party: Otsuka Pharmaceutical Co., Ltd.
ClinicalTrials.gov Identifier: NCT01628848     History of Changes
Other Study ID Numbers: 243-05-001, JapicCTI-060287
Study First Received: June 24, 2012
Results First Received: February 3, 2014
Last Updated: February 3, 2014
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Otsuka Pharmaceutical Co., Ltd.:
SPM 962
rotigotine
Parkinson's disease
concomitant use of L-dopa

Additional relevant MeSH terms:
Parkinson Disease
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Movement Disorders
Nervous System Diseases
Neurodegenerative Diseases
Parkinsonian Disorders

ClinicalTrials.gov processed this record on October 23, 2014