Rotigotine Versus Placebo to Evaluate the Efficacy on Depressive Symptoms in Idiopathic Parkinson's Disease Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma ( UCB Korea Co., Ltd. )
ClinicalTrials.gov Identifier:
NCT01523301
First received: January 27, 2012
Last updated: November 16, 2015
Last verified: November 2015
  Purpose
The purpose of this study was to show superiority of Rotigotine over placebo on improvement of depressive symptoms in subjects with idiopathic Parkinson's disease.

Condition Intervention Phase
Idiopathic Parkinson's Disease
Drug: Rotigotine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Double Blind, Placebo-controlled, Parallel, Multicenter, Randomized Interventional Phase IV Study to Evaluate the Efficacy of Rotigotine on Depressive Symptoms in Idiopathic Parkinson's Disease Patients

Resource links provided by NLM:


Further study details as provided by UCB Pharma:

Primary Outcome Measures:
  • Change From Baseline to the End of Maintenance Period in the Score of the Hamilton Depression Scale (HAM-D) [ Time Frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 15) ] [ Designated as safety issue: No ]
    The HAM-D consists of 17 items. Nine of the items are scored on a 5-point scale, ranging from 0 to 4. The remaining 8 items are scored on a 3-point scale, from 0 to 2. Therefore, the total score ranges between 0 to 52, with a cutoff score of 15/16 diagnosing major depressive disorder.


Secondary Outcome Measures:
  • Change From Baseline to the End of Maintenance Period in the Score of Beck Depression Inventory (BDI-II) [ Time Frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 15) ] [ Designated as safety issue: No ]
    The Beck Depression Inventory II (BDI-II) is a self-report instrument to measure Depression symptoms and severity. There are 21 items in the BDI-II. Scores of 0-13 are considered minimal depression; 14-19 indicates mild depression; 20-28 indicates moderate depression; and 29-63 indicates severe depression.

  • Change From Baseline to the End of Maintenance Period in the Score of Unified Parkinson's Disease Rating Scale (UPDRS) Part II (Activities of Daily Living-ADL Subscale) [ Time Frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 15) ] [ Designated as safety issue: No ]
    The UPDRS Part II is a tool to measure Activities in Daily Living - it includes speech, salivation, swallowing, handwriting, cutting food and handling utensils, dressing, hygiene, turning in bed and adjusting clothes, falling (unrelated to freezing), freezing when walking, walking, tremor, and sensory complaints related to Parkinsonism. Each of the 13 questions is measured on a scale from 0 (normal) to 4 (severe). The total score of UPDRS part II ranges from 0 (normal) to 52 (severe).

  • Change From Baseline to the End of Maintenance Period in the Score of Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Subscale) [ Time Frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 15) ] [ Designated as safety issue: No ]
    Improvement of motor symptoms is measured by the change from Baseline in UPDRS Part III motor score. The UPDRS Part III is an accepted and validated scale for the assessment of motor function in Parkinson's disease. Each of the elements in the UPDRS Part III is measured on a scale of 0 to 4, where 0 is normal and 4 represents severe abnormalities. The total score of UPDRS part III ranges from 0 (normal) to 108 (severe abnormalities).

  • Change From Baseline to the End of Maintenance Period in the Combined Score of Unified Parkinson's Disease Rating Scale (UPDRS) Part II (ADL) Plus Part III (Motor Subscale) [ Time Frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 15) ] [ Designated as safety issue: No ]
    The combined score of UPDRS part II and UPDRS part III is the sum of the individual scores and threfore ranges from 0 (normal) to 160 (severe).

  • Change From Baseline to the End of Maintenance Period in the Score of Apathy Scale (AS) [ Time Frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 15) ] [ Designated as safety issue: No ]
    The AS is an abbreviated version of the Apathy Scale (AS). The AS consists of 14 items phrased as questions that are to be answered on a four-point Likert scale. It was developed specifically for patients with Parkinson Disease (PD). For questions 1-8, the scoring system is the following: not at all = 3 points; slightly = 2 points; some =1 point, a lot = 0 point. For questions 9-14: the scoring system is the following: not at all = 0 points; slightly = 1 point; some = 2 points; a lot = 3 points. Adding all scores provides the final score with a range from 0 to 42.

  • Change From Baseline to the End of Maintenance Period in the Score of Snaith-Hamilton Pleasure Scale (SHAPS) [ Time Frame: From Baseline (Week 0) to end of Maintenance Period (up to Week 15) ] [ Designated as safety issue: No ]
    The SHAPS is a self-report instrument developed for the assessment of hedonic capacity. The sum of the 14 items scores ranges from 0 to 14. A higher score represents more anhedonic symptoms.


Enrollment: 380
Study Start Date: April 2012
Study Completion Date: October 2014
Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rotigotine
Rotigotine, daily doses, treatment group
Drug: 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, Subjects received 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 8 week Maintenance period
  • For advanced-stage Parkinson's disease, Subjects received Rotigotine patches in escalating weekly dose (starting with daily doses 4 mg/24 h to 16 mg/24 h) for a maximum 7-week Titration Period, then 8 week Maintenance period
Placebo Comparator: Placebo
Placebo, daily doses, placebo group
Drug: Placebo

Transdermal Patch

Size:

10 cm^2, 20 cm^2, 30 cm^2, 40 cm^2

Subjects randomized to placebo received matching placebo patches


Detailed Description:

The study included a maximum 2-week Screening Period, a maximum 4-week Titration Period for early-stage Parkinson's disease or maximum 7-week Titration Period for advanced-stage Parkinson's disease, 8-week Maintenance Period, a maximum 6-day De-escalation Period for early-stage Parkinson's disease or maximum 12-day De-escalation Period for advanced-stage Parkinson's disease and 30-day Safety Follow-Up Period.

The maximum study durations for an individual subject with early-stage Parkinson's disease and with advanced-stage Parkinson's disease were 19 weeks and 23 weeks, respectively.

  Eligibility

Ages Eligible for Study:   20 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects ≥ 20 years old
  • Subjects diagnosed with idiopathic Parkinson's disease (according to the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria for Parkinson's disease) at modified Hoehn and Yahr Scale stages I-III; do not have motor fluctuations, dyskinesia, and have stable motor symptom at least 4 weeks prior to the Screening Visit as judged by the local investigator
  • Subject has a Beck Depression Inventory II (BDI-II) score ≥ 16 as evidenced by depression rating scale study in Parkinson's disease (Schrag A et al, 2007)
  • Subject has a Mini-Mental State Examination (MMSE) score ≥ 24
  • If subject is taking Levodopa (L-DOPA) and derivatives, Monoamine Oxidase (MAO) B-inhibitors, anticholinergics agents, Catechol-O-Methyl Transferase (COMT) inhibitor or N-Methyl-D-Aspartate (NMDA) antagonist, he/she must have been on stable dose for at least 28 days prior to the Screening Visit
  • If subject is taking an antidepressant drug such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), bupropion, tricyclic antidepressants (TCAs), he/she must have been on a stable dose for at least 28 days prior to the Screening Visit and be maintained on that dose for the duration of the trial

Exclusion Criteria:

  • Subject has any medical or psychiatric condition (ie, bipolar disorder, dementia, hallucinations or psychosis) that, in the opinion of the investigator, could jeopardize or would compromise the subject's ability to participate in this study
  • Subject has a lifetime history of suicide attempt (including an active 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 C-SSRS at Screening (Visit 1)
  • Current psychotherapy or behavior therapy while participating in this study
  • Subject has received electroconvulsive therapy within 12 weeks of the Screening Visit
  • Subject who has received dopamine agonists within 28 days of the Screening Visit
  • Subject who has received neuroleptics, methylphenidate, reserpine, alpha-methyldopa, metoclopramide, levosulpiride or amphetamine derivatives within 28 days of the Screening Visit
  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: NCT01523301

Locations
Korea, Republic of
03
Ansan, Korea, Republic of
19
Anyang, Korea, Republic of
08
Busan, Korea, Republic of
26
Busan, Korea, Republic of
23
Chungbuk, Korea, Republic of
04
Daegu, Korea, Republic of
05
Daegu, Korea, Republic of
16
Daejon, Korea, Republic of
28
Goyang, Korea, Republic of
24
Gwangju, Korea, Republic of
29
Gwangju, Korea, Republic of
11
Gyeonggi-Do, Korea, Republic of
15
Jinju, Korea, Republic of
01
Seoul, Korea, Republic of
02
Seoul, Korea, Republic of
06
Seoul, Korea, Republic of
07
Seoul, Korea, Republic of
09
Seoul, Korea, Republic of
10
Seoul, Korea, Republic of
12
Seoul, Korea, Republic of
13
Seoul, Korea, Republic of
14
Seoul, Korea, Republic of
17
Seoul, Korea, Republic of
18
Seoul, Korea, Republic of
20
Seoul, Korea, Republic of
21
Seoul, Korea, Republic of
22
Seoul, Korea, Republic of
27
Seoul, Korea, Republic of
25
Yangsan, Korea, Republic of
Sponsors and Collaborators
UCB Korea Co., Ltd.
Investigators
Study Director: UCB Clinical Trial Call Center +1 877 822 9493 (UCB)
  More Information

Responsible Party: UCB Korea Co., Ltd.
ClinicalTrials.gov Identifier: NCT01523301     History of Changes
Other Study ID Numbers: SP1041 
Study First Received: January 27, 2012
Results First Received: October 12, 2015
Last Updated: November 16, 2015
Health Authority: South Korea: Ministry of Food and Drug Safety (MFDS)

Keywords provided by UCB Pharma:
Rotigotine
Neupro
Depressive Symptom
Idiopathic Parkinson's disease

Additional relevant MeSH terms:
Parkinson Disease
Depression
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Behavioral Symptoms
N 0437
Dopamine Agonists
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2016