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

Idiopathic Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01523301
• Other study ID #: SP1041
• Status: Completed
• Phase: Phase 4
• First received: January 27, 2012
• Last updated: November 16, 2015
• Start date: April 2012
• Est. completion date: October 2014

Study information

• Verified date: November 2015
• Source: UCB Pharma
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Ministry of Food and Drug Safety (MFDS)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 380
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Idiopathic Parkinson's Disease
• Parkinson Disease

Intervention

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
Transdermal Patch Size: 10 cm^2, 20 cm^2, 30 cm^2, 40 cm^2 Subjects randomized to placebo received matching placebo patches

Locations

Country	Name	City	State
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

Sponsors (1)

Lead Sponsor	Collaborator
UCB Korea Co., Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline to the End of Maintenance Period in the Score of the Hamilton Depression Scale (HAM-D)	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.	From Baseline (Week 0) to end of Maintenance Period (up to Week 15)	No
Secondary	Change From Baseline to the End of Maintenance Period in the Score of Beck Depression Inventory (BDI-II)	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.	From Baseline (Week 0) to end of Maintenance Period (up to Week 15)	No
Secondary	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)	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).	From Baseline (Week 0) to end of Maintenance Period (up to Week 15)	No
Secondary	Change From Baseline to the End of Maintenance Period in the Score of Unified Parkinson's Disease Rating Scale (UPDRS) Part III (Motor Subscale)	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).	From Baseline (Week 0) to end of Maintenance Period (up to Week 15)	No
Secondary	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)	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).	From Baseline (Week 0) to end of Maintenance Period (up to Week 15)	No
Secondary	Change From Baseline to the End of Maintenance Period in the Score of Apathy Scale (AS)	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.	From Baseline (Week 0) to end of Maintenance Period (up to Week 15)	No
Secondary	Change From Baseline to the End of Maintenance Period in the Score of Snaith-Hamilton Pleasure Scale (SHAPS)	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.	From Baseline (Week 0) to end of Maintenance Period (up to Week 15)	No