Carbidopa/Levodopa/Entacapone Versus Immediate Release (IR) Carbidopa/Levodopa on Non-Motor Symptoms in Patients With Idiopathic Parkinson's Disease

Condition(s) targeted: Parkinson's Disease

Intervention: Carbidopa/levodopa/entacapone, IR carbidopa/levodopa (Drug); Carbidopa/levodopa/entacapone, IR carbidopa/levodopa (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Novartis

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

Overall contact:
Novartis Pharmaceuticals, Phone: 862-778-8300

The purpose of this study is to test the effects of carbidopa/levodopa/entacapone compared to the effects of immediate-release carbidopa/levodopa on end-of-dose wearing off in persons who have Parkinson's disease.

Official title: An 8-Week, Prospective, Randomized, Double-Blind, Double-Dummy, Active-Controlled, Multi-Center Comparison Study of the Effects of Carbidopa/Levodopa/Entacapone Versus Immediate Release Carbidopa/Levodopa on Non-Motor Symptoms in Patients With Idiopathic Parkinson's Disease and Demonstrating Non-Motor Symptoms of Wearing

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Compare effects of carbidopa/levodopa/entacapone versus IR carbidopa/levodopa on the non-motor symptoms in patients with idiopathic PD and non-motor symptoms of wearing off using the non-motor subscale of the QWOQ-9 item from baseline to end of study

Secondary outcome:

Compare effects of carbidopa/levodopa/entacapone versus IR carbidopa/levodopa on the motor symptoms in patients with idiopathic PD and non motor symptoms of wearing off using the motor subscale of the QWOQ-9 (mQWOQ-9) from baseline to end of study.

Compare effects of carbidopa/levodopa/entacapone versus IR carbidopa/levodopa on the non-motor symptoms in patients with idiopathic PD and non-motor symptoms of wearing off using the Hamilton Anxiety Scale (HAM-A) from baseline to end of study.

Compare effects of carbidopa/levodopa/entacapone versus IR carbidopa/levodopa on apathy and depression using the Apathy Scale and Quick Inventory of Depressive Symptomatology-Self Reporting 16-item (QIDS-SR16) respectively, from baseline to end of study.

Assess occurrence and severity of symptoms of impulse control, as measured with the Modified Minnesota Impulsive Disorder Interview assessment (Modified MIDI), of carbidopa/levodopa/entacapone versus IR carbidopa/levodopa from baseline to end of study.

Minimum age: 30 Years. Maximum age: 85 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Be aged 30 to 85 years.

- Be male or female - female patients must be either not of childbearing potential

(defined as post menopausal for at least one year or surgically incapable of bearing children), or must be practicing contraceptive methods as outlined in the protocol.

- Have a clinical diagnosis of idiopathic Parkinson's Disease, exhibiting at least 2 of

3 symptoms (rigidity, resting tremor, bradykinesia)

- Have non-motor symptoms of end of dose wearing off i. e., the presence of at least one

non-motor symptom of Parkinson's Disease which improves with the next immediate release (IR) carbidopa/levodopa dose as determined by the Quantitative Wearing-Off Questionnaire 9 and investigator's assessment. At least one non-motor item has to show a severity of at least 2 points (of a maximum of 4) and show an improvement of at least 1 one hour after immediate release (IR) carbidopa/levodopa administration. (all criteria must be fulfilled)

- Be taking a stable dose of immediate release (IR) carbidopa/levodopa for at least 28

days prior to randomization at an equivalent total daily dose of immediate release (IR) carbidopa/levodopa between 300 to 600 mg. Dosing should be either 3 or 4 times per day.

- Be capable of satisfying the requirements of the protocol and must be willing and able

to give informed consent according to legal requirements.

Exclusion Criteria:

- Have a previous history of being non-responsive to entacapone or tolcapone treatment

or having experienced a serious or severe adverse event(s) which resulted in the discontinuation of treatment from the previous use of entacapone or tolcapone; current treatment with entacapone or tolcapone or discontinued treatment with either therapy or discontinued less than 60 days before randomization;

- Have a history, signs, or symptoms suggesting a diagnosis of secondary or atypical

parkinsonism;

- Have unstable Parkinson's Disease requiring frequent booster doses;

- Disabling dyskinesias, indicated by a score of greater than 1 on Unified Parkinson

Disease Rating Scale question #32, or a score of greater than 1 on Unified Parkinson Disease Rating Scale question #33;

- Have a history or current diagnosis of psychotic features according to the

investigator;

- Have a history or current diagnosis of symptoms of an impulse control disorder

according to a screening assessment with the modified Minnesota Impulsive Disorders Interview and the investigator's judgment;

- Have a diagnosis of Bipolar Disorder I or II according to the Diagnostic Statistical

Manual, Fourth Edition;

- Demonstrate indications of marked suicidal tendencies as assessed by the

investigator;

- Have undergone psychotherapy or psychiatric pharmacotherapy, currently or within 28

days prior to randomization;

- If female, be pregnant, trying to become pregnant or nursing an infant;

- Diagnostic and Statistical Manual, Fourth Edition, Text Revision; [American

Psychiatric Association, 2000] diagnosis of 1. dementia (of any cause); 2. moderate or severe major depression, present independent from the time of first diagnosis of Parkinson's Disease, as defined by a Quick Inventory of Depressive Symptomatology

- Self Rating 16 score of > 15; or 3. generalized anxiety disorder or panic disorder if

made prior to the diagnosis of Parkinson's Disease;

- Have received treatment with MAO-inhibitors;

- Diagnostic and Statistical Manual, Fourth Edition, Text Revision diagnosis of alcohol

or substance abuse (excluding nicotine or caffeine) during the 3 months prior to randomization) or alcohol or substance dependence (excluding nicotine or caffeine) during the 6 months prior to randomization. Alcohol should be avoided within the 12 hours preceding the Screening, Baseline, Week 2 and Week 8 visits;

- Diagnostic and Statistical Manual, Fourth Edition, Text Revision diagnosis of

dysthymia within the last 12 months;

- Have a history or current diagnosis of malignancy of any organ system, treated or

untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin.

Other protocol-defined inclusion/exclusion criteria may apply

Novartis Pharmaceuticals, Phone: 862-778-8300

Xenoscience, Inc, Phoenix, Arizona 85004, United States; Recruiting

University of California, Irvine, California 92697, United States; Recruiting

Coastal Neurological Medical Group, Inc, La Jolla, California 92037, United States; Recruiting

South Coast Health Center, Aliso Viejo, California 92656, United States; Recruiting

Georgetown University Hospital, Washington, District of Columbia 20007, United States; Recruiting

Sunrise Clinical Research, Inc, Hollywood, Florida 33021, United States; Recruiting

Charlotte Neurological Services, Port Charlotte, Florida 33952, United States; Recruiting

Cotton O'Neil Clinic, Topeka, Kansas 66606, United States; Recruiting
Kelly Knoebber-Carr, Phone: 785-368-0741, Email: kknoebbe@stormontvail.org

University of Maryland School of Medicine, Baltimore, Maryland 21201, United States; Recruiting

Dr. John's Mercy Medical Center, St. Louis, Missouri 63141, United States; Recruiting

Neurology, Inc, Columbia, Missouri 65201, United States; Recruiting

Creighton U Medical Center, Dept of Neurology, Omaha, Nebraska 68131, United States; Recruiting

Parkinson's Disease & Movement Disorders, Commack, New York 11725, United States; Recruiting

Neurological Care of Central NY, Syracuse, New York 13210, United States; Recruiting

Central New York Research Corporation, Syracuse, New York 13210, United States; Recruiting

Duke University, Durham, North Carolina 27705, United States; Recruiting

University of Pittsburg, Pittsburg, Pennsylvania 15213, United States; Recruiting

Neurology Associates, Monroeville, Pennsylvania 15146, United States; Recruiting

University of Texas Southwestern, Dallas, Texas 75390, United States; Recruiting

Scott & White Hospital, Temple, Texas 76508, United States; Recruiting

University of Texas Medical School, Houston, Texas 77030, United States; Recruiting

Starting date: February 2008
Last updated: November 10, 2008