Study on the Tolerability of Duloxetine in Depressed Patients With Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT00437125
• Recruitment Status: Completed
• First Posted: February 19, 2007
• Results First Posted: August 16, 2010
• Last Update Posted: September 8, 2010
• Sponsor: Eli Lilly and Company
• Information provided by: Eli Lilly and Company

Study Description

Brief Summary:

This study aims to assess the tolerability of duloxetine, 60mg once daily, in open label fashion, in depressed patients with Parkinson's disease during 12 weeks treatment.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder; Idiopathic Parkinson Disease	Drug: Duloxetine hydrochloride	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 151 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Pilot Study on the Tolerability of Duloxetine in the Treatment of Depressed Patients With Parkinson's Disease
• Study Start Date: March 2007
• Actual Primary Completion Date: July 2009
• Actual Study Completion Date: July 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Duloxetine; Participants received duloxetine 30 milligram (mg) orally once daily (QD) for 1 week, followed by duloxetine 60 mg orally QD for 11 weeks	Drug: Duloxetine hydrochloride; Duloxetine 30 milligram (mg) once daily (QD) orally (PO) for 1 week, then duloxetine 60 mg QD PO for 11 weeks; Other Name: LY248686; Cymbalta

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Reporting Serious Adverse Events or Other Adverse Events Leading Either to Discontinuation or to Death [ Time Frame: baseline through 12 weeks ]
   The results reported are the number of participants who discontinued the study as a result of an adverse event (serious or other) or death.

Secondary Outcome Measures :

1. Change From Baseline to 12 Weeks on the Unified Parkinson's Disease Rating Scale (UPDRS) Total Score [ Time Frame: baseline, 12 weeks ]
   Rating tool to follow the longitudinal course of Parkinson's Disease. It is composed of Section I: Mentation, Behavior, and Mood; Section II: Activities of Daily Living; Section III: Motor Examination; Section IV: Complications of therapy. These are evaluated by interview. Some sections require that multiple grades be assigned to each extremity. Only Sections II and III were rated in this study. A total of 160 points are possible (52 in Section II and 108 in Section III), where 0 represents no disability and 160 indicates maximal grade of disability.
2. Change From Baseline to 12 Weeks on the UKU (Udvalg for Kliniske Undersogelser: Committee for Clinical Investigations) Side Effect Rating Scale [ Time Frame: baseline, 12 weeks ]
   Clinician-rated scale, providing side effect ratings of psychopharmacological medications. 48 items, each item is rated on a 4-point scale (0=not present; 1=mild; 2=moderate; 3=severe). The test is divided in 6 subscales, total scores for each subscale are calculated based on a weighted secondary scoring system. Subscales: psychic (score range:0-30), neurological (score range:0-24), autonomic (score range:0-33), other (score range:0-75), global assesment by subject (score range:0-3), and global assessment by doctor (score range:0-3). Higher ratings indicate greater impairment.
3. Change From Baseline on the Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: baseline, 4 weeks, 8 weeks, 12 weeks ]
   Self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. 19 individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The subject self-rates each of these seven areas of sleep. Scoring of answers is based on a 0 to 3 scale, whereby 3 reflects the negative extreme on the Likert Scale. The total score is the sum of the 7 component scores (total score range: 0-21).
4. Change From Baseline to 12 Weeks on the 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score [ Time Frame: baseline, 12 weeks ]
   The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
5. Change From Baseline to 12 Weeks on the Clinical Global Impression-Severity Scale [ Time Frame: baseline, 12 weeks ]
   Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).
6. Patient's Global Impression-Improvement at Week 12 [ Time Frame: 12 weeks ]
   A scale that measures the patient's perception of improvement at the time of assessment compared with the start of treatment. Scoring: 1=very much better; 2=much better; 3=low better; 4=no change; 5=low worse; 6=much worse; 7=very much worse.
7. Change From Baseline to 12 Weeks in Beck Depression Inventory (BDI) Total Score [ Time Frame: baseline, 12 weeks ]
   A 21-item, patient-completed questionnaire to assess characteristics of depression. Each of the 21 items corresponding to a symptom of depression is summed to give a single score. There is a four-point scale for each item ranging from 0 to 3. Total score of 0-13 is considered minimal range, 14-19 is mild, 20-28 is moderate, and 29-63 is severe.
8. Change From Baseline to 12 Weeks in Visual Analog Scale (VAS) [ Time Frame: baseline, 12 weeks ]
   VAS for pain consists of 6 questions that assess overall pain, headache, back pain, shoulder pain, pain interference with daily activities, and pain while awake. Participant rates pain on a 100 millimeter (mm) line between two anchors (0= no pain and 100=very severe pain). Here, the line was only 93 mm long due to an error on the clinical research form and scores were adjusted to 0 to 93.
9. Change From Baseline to 12 Weeks in Parkinson Disease Questionnaire - 39 Item Version (PDQ-39) Total Score [ Time Frame: baseline, 12 weeks ]
   The PDQ-39 has 39 items. Higher scores reflect lower quality of life. The PDQ-39 has eight subscales: mobility (10 items), activities of daily living (six items), emotional wellbeing (six items), stigma (four items), social support (three items), cognition (four items), communication (three items), and bodily discomfort (three items). Items in each subscale, as well in the total scale, can be summarized into an index and transformed linearly to a 0-100 scale.
10. Average Change From Baseline to 12 Weeks in Blood Pressure [ Time Frame: baseline through 12 weeks ]
    For each participant, changes across individual visits were averaged to obtain 1 measurement per participant.
11. Average Change From Baseline to 12 Weeks in Heart Rate [ Time Frame: baseline through 12 weeks ]
    For each participant, changes across individual visits were averaged to obtain 1 measurement per participant.
12. Number of Participants With Abnormal Electrocardiograms (ECG) During the 12 Week Study [ Time Frame: baseline through 12 weeks ]
    Included were participants with normal ECG at baseline who developed abnormal ECGs during the study.
13. Laboratory Analytes [ Time Frame: baseline through 12 weeks ]
    Laboratory analytes were collected to assess adverse events which are listed in the reported adverse events section.
14. Number of Participants Who Responded to Treatment by 12 Weeks [ Time Frame: 12 weeks ]
    Response was defined as a >= 50% reduction in 17-item Hamilton Depression rating scale (HAMD) scores. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
15. Number of Participants Who Reached Remission by 12 Weeks [ Time Frame: 12 weeks ]
    Remission was defined as reaching a 17-item Hamilton Depression Rating Scale (HAMD) total score <=7. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Are outpatients, male or female, 30 through 75 years of age
• Meet diagnostic criteria for major depression episode and a clinical diagnosis of idiopathic Parkinson's disease
• Have a clinician-rated 17-item Hamilton Depression Rating Scale (HAMD17) total score greater than or equal to 15, a Beck Depression Inventory (BDI) total score greater than or equal to 13 and a Clinical Global Impression of Severity (CGI-S) score greater than or equal to 3 at both Visit 1 and Visit 2
• Have satisfactory cognitive function
• Have been held on stable dosage of antiparkinsonian medications for at least 4 weeks immediately prior to Visit 1

Exclusion Criteria:

• Any current primary psychiatric diagnosis other than Major depressive episode, and any personality disorder that could interfere with the compliance with the study protocol
• Atypical or secondary parkinsonism due to drugs or diseases with features of Parkinson's disease
• Motor conditions for which it is to be expected to change the antiparkinsonian treatment during the course of the study
• Clinically significant laboratory abnormalities or serious, unstable medical illness
• Lack of response of current episode to two or more adequate courses of antidepressant therapy

Contacts and Locations

Locations

Italy

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Ancona, Italy, 60124

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Brescia, Italy, 25100

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Catania, Italy, 95125

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Genova, Italy, 16132

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Lido Di Camaiore, Italy, 55000

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Messina, Italy, 98122

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Milano, Italy, 20157

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Napoli, Italy, 80131

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Padova, Italy, 35100

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Pisa, Italy, 56100

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Pozzilli, Italy, 86077

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Rome, Italy, 00179

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Torino, Italy, 10126

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

Additional Information:

Lilly Clinical Trial Registry 

• Responsible Party: Chief Medical Officer, Eli Lilly
• ClinicalTrials.gov Identifier: NCT00437125
• Other Study ID Numbers: 11127; F1J-IT-HMFQ ( Other Identifier: Eli Lilly and Company )
• First Posted: February 19, 2007
• Results First Posted: August 16, 2010
• Last Update Posted: September 8, 2010
• Last Verified: September 2010

Additional relevant MeSH terms:

Parkinson Disease; Depressive Disorder; Depressive Disorder, Major; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Mood Disorders; Mental Disorders; Duloxetine Hydrochloride; Serotonin and Noradrenaline Reuptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Antidepressive Agents; Psychotropic Drugs; Dopamine Agents