Melperone (an Anti-Psychotic) in Patients With Psychosis Associated With Parkinson's Disease

Parkinson's Disease Clinical Trial

Official title:

Safety and Efficacy of Melperone in the Treatment of Patients With Psychosis Associated With Parkinson's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00125138
• Other study ID #: 13104A
• Secondary ID: OV1003
• Status: Completed
• Phase: Phase 2
• First received: July 27, 2005
• Last updated: May 17, 2011
• Start date: July 2005
• Est. completion date: April 2008

Study information

• Verified date: May 2011
• Source: Lundbeck LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of three target doses of melperone compared to placebo in the treatment of psychosis associated with Parkinson's disease. Subjects will be enrolled at approximately 20 investigational sites in the United States (U.S.) and 15 Ex-US sites. The maximum study duration will be 10 weeks. Subjects will have the option of continuing in an open-label extension study.

Description:

Parkinson's Disease is a progressive neurodegenerative disorder characterized by bradykinesia, rigidity, tremor and abnormal posture and gait. Many patients can have mild to moderate symptoms, while others with advanced disease have symptoms which interfere with activities of daily living to a severe degree. Although effective in addressing motor dysfunction, long-term use of anti-Parkinsonian agents has been implicated as a component in the development of psychiatric side effects including psychosis. Treatment of psychosis with typical antipsychotics is not recommended in this patient population, since even low potency typical antipsychotics can cause marked exacerbations of parkinsonism in Parkinson's disease patients. The use of atypical antipsychotics (e.g., clozapine, risperidone and quetiapine) has shown some efficacy in the treatment of psychosis in PD patients. Melperone is classified atypical antipsychotic. European experience with melperone spans more than 30 years, and it encompasses an established antipsychotic efficacy profile in the treatment of confusion, anxiety, unrest (particularly in the elderly) and schizophrenia as well as a favorable safety and tolerability profile. Eligible subjects with Parkinson's disease psychosis will participate in a 1-2 week Screening/Washout Period, a 5 week Titration Phase (one of three doses of melperone or placebo), a 1 week Maintenance Phase and a Taper/Follow-up Period up to 2 weeks. Following the Day 43 assessment, subjects may be given the option of receiving melperone in an open-label extension study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: April 2008
• Est. primary completion date: March 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• The subject or subject's legally authorized representative (LAR) must sign and date the IRB/IEC approved Informed Consent Form and HIPAA Authorization (applicable to US sites only) prior to study participation.

• Male or female subjects. If female:

• Subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy), or if of childbearing potential, must comply with a method of birth control acceptable to the investigator during the study, for at least one month prior to randomization and for one month following completion of the study.

• Subject is not breastfeeding

• Subjects of childbearing potential must have a negative serum pregnancy test at the screening visit and on Day 1.

• Subjects with a clinical diagnosis of idiopathic Parkinson's Disease, defined as the presence of at least three of the following cardinal features, in the absence of alternative explanations or atypical features:

• Rest tremor

• Rigidity

• Bradykinesia and/or akinesia

• Postural and gait abnormalities

• Subjects with psychosis:

• Presence of visual and/or auditory hallucinations, with or without delusions, occurring during the four weeks prior to the screening visit.

• Symptoms severe enough to clinically warrant treatment with an antipsychotic agent.

• A Hallucinations or Delusions total item score (frequency x severity) of > 4 on the Neuropsychiatric Inventory (NPI).

• Subjects currently being treated with an antipsychotic agent who have not had visual and/or auditory hallucinations, with or without delusions, during the four weeks prior to screening, and/or have a Hallucinations or Delusions total item score <4 on the NPI at the screening visit may be washed out (for 7 days or 5 half-lives, whichever is longer) and return for a repeat screening visit. The NPI Hallucinations or Delusions total item score must be =4 at the repeat visit to be considered for study entry.

• Subject is on a stable dose of anti-Parkinsonian medication(s) for at least 7 days or 5 half-lives, whichever is longer, prior to the screening visit and is expected to remain on a stable dose for the duration of the study.

• Subject is willing and able to comply with all study procedures.

Exclusion Criteria:

• Subject has any systemic factor contributing to the psychosis such as urinary infection, liver disease, renal failure, anemia, infection or cancer.

• Subject has a history of significant psychotic disorders prior to the diagnosis of Parkinson's Disease, including but not limited to schizophrenia or bipolar disorder.

• Subject has Dementia with Lewy-bodies (DLB).

• Subject has dementia or a major depressive disorder precluding accurate assessment on rating scales.

• Subject has an acute depressive episode at the time of the screening visit.

• A score on the Mini-Mental State Examination (MMSE) of < 21.

• Subject has had a dose adjustment of their antidepressant medication within 30 days prior to the screening visit, or dose adjustments are planned during the duration of the trial.

• Subject has had dose adjustments of an anxiolytic, cognitive enhancer, or other psychotropic medication (excluding antipsychotics) within 30 days prior to screening or dose adjustments are planned during the duration of the trial.

• Subject has received depot antipsychotic agents within the past 3 months.

• Subject has previously failed treatment with clozaril for psychosis in Parkinson's disease. Subjects who discontinued clozaril due to intolerability may be enrolled.

• Subject has used any investigational product within 30 days or 5 half-lives, whichever is longer, prior to screening.

• Subject cannot tolerate a wash-out of antipsychotic medication prior to randomization.

• Subject has a history of a serious respiratory, gastrointestinal, renal, hematologic or other medical disorder.

• Subject has a history of a serious cardiovascular condition (including, but not limited to, Class IV angina or Class IV heart failure) and/or a history of risk factors for Torsade de pointes (Tdp) (including but not limited to current treatment for hypokalemia or family history of long QT syndrome).

• Subject had myocardial infarction within 6 months prior to screening.

• Subject has a screening ECG with corrected QT interval by Bazett's correction formula (QTcB) of greater than 450 msec, if female, or 430 msec, if male.

• Subject requires treatment with an a-agonist agent.

• Subject has uncontrolled seizures, uncontrolled angina, or uncontrolled symptomatic orthostatic hypotension (or orthostatic hypotension leading to a history of falls 3 months prior to screening), or other medical disorders which would make the subject a poor candidate for a clinical trial.

• Subject has a history of severe adverse reactions to antipsychotic medications and/or quinine.

• Subject has clinically significant abnormal laboratory values, ECG, or findings on physical exam.

• Subject has a recent history or current evidence of substance dependence or abuse.

• Subject is unable to ingest liquid medication.

• Subject is currently being treated with Deep Brain Stimulation (DBS).

Randomization Criteria

• Subject has a Hallucinations or Delusions total item score (frequency x severity) of > 4 on the NPI.

• Female subjects of childbearing potential must have a negative serum pregnancy test.

• Subject has remained on a stable dose of anti-Parkinsonian medications.

• Subject has not had a dose adjustment in their antidepressant medication since the screening visit.

• Subjects have been washed out of previous antipsychotic agents for 5 half-lives or 7 days, whichever is longer, after the last dose of medication.

• Subject has not had dose adjustments in an anxiolytic, cognitive enhancer or other psychotropic medication (excluding antipsychotics) since the Screening Visit.

Study Design

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

Related Conditions & MeSH terms

• Mental Disorders
• Parkinson Disease
• Parkinson's Disease
• Psychotic Disorders

Intervention

Drug:
• Melperone HCl
20 mg/day. Strength of melperone syrup is 5 mg/mL
• Melperone HCl
40 mg/day. Strength of melperone syrup is 5 mg/mL
• Melperone HCl
60 mg/day. Strength of melperone syrup is 5 mg/mL
• Placebo
Syrup formulation

Locations

Country	Name	City	State
India	Department of Neurology, Manipal Hospital	Bangalore	Karnataka
India	M. S. Ramasah Memorial Hospital	Bangalore	Karnataka
India	KLE Hospital, Belgaum	Belgaum	Karnataka
India	Apollo Hospitals Educational and Research Foundation	Chennai	Tamilnadu
India	Kasturra Medical College, Hospital, Attavar	Mangalore	Karnataka
India	Jaslok Hospital and Research Center	Mumbai	Maharastra
India	SCTIMST	Trivandrum	Kerla
India	Department of Neurology, Rajendra Prasad Ward, King George Hospital, Visakhapatnam	Visakhapatnam	Andhra Pradesh
Italy	Fondazione Universita di Chieti C.E.S.I. Centro Studi sull'Invecchiamento	Chieti Scalo	Ambruzzo
Italy	IRCCS Centro Neurolesi "Bonino Pulejo"	Messina	Sicily
Italy	U.O. Neurologia IRCCS San Raffaele Pisana	Rome	Lazio
United States	Quest Research Institute	Bingham Farms	Michigan
United States	Bradenton Research Center, Inc	Bradenton	Florida
United States	Neurology Consultants of the Carolinas	Charlotte	North Carolina
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	Struthers Parkinson's Center, Park Nicollet Health Services	Golden Valley	Minnesota
United States	The University of Kansas Medical Center	Kansas City	Kansas
United States	Neurology Associates	San Antonio	Texas
United States	Washington University School of Medicine	St. Louis	Missouri
United States	University of South Florida	Tampa	Florida
United States	Northwest Neurospecialists, PLLC	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Lundbeck LLC

Countries where clinical trial is conducted

United States,  India,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Patient Evaluation of Symptoms of Psychosis.	The change in the Scale for Assessment of Positive Symptoms (SAPS) total score. The SAPS total score ranges from 0 to 170, with higher scores indicating more severe psychosis.	6 weeks (from Baseline to end of Maintenance Period)	No
Secondary	Investigator/Caregiver Evaluations of Motor Function	The change in the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS III - motor exam) score. Scores on the UPDRS III - motor exam range from 0 to 108, with higher scores indicating more severe motor symptoms.	6 weeks (from Baseline to end of Maintenance Period)	No