Clinical trial NCT00125138: Melperone (an Anti-Psychotic) in Patients With Psychosis Associated With Parkinson's Disease
Official title: Safety and Efficacy of Melperone in the Treatment of Patients With Psychosis Associated With Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Parkinson's Disease
Psychotic Disorders
Lead sponsor: Lundbeck LLC
Sponsor class: INDUSTRY
First posted: 2005-07-29
Enrollment: 90
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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 α-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.

Primary outcomes:
measure: Patient Evaluation of Symptoms of Psychosis.
timeFrame: 6 weeks (from Baseline to end of Maintenance Period)
Secondary outcomes:
measure: Investigator/Caregiver Evaluations of Motor Function
timeFrame: 6 weeks (from Baseline to end of Maintenance Period)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Northwest Neurospecialists, PLLC
state: Arizona
city: Bradenton
country: United States
facility: Bradenton Research Center, Inc
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
city: Bingham Farms
country: United States
facility: Quest Research Institute
state: Michigan
city: Golden Valley
country: United States
facility: Struthers Parkinson's Center, Park Nicollet Health Services
state: Minnesota
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Charlotte
country: United States
facility: Neurology Consultants of the Carolinas
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: San Antonio
country: United States
facility: Neurology Associates
state: Texas
city: Visakhapatnam
country: India
facility: Department of Neurology, Rajendra Prasad Ward, King George Hospital, Visakhapatnam
state: Andhra Pradesh
city: Bangalore
country: India
facility: Department of Neurology, Manipal Hospital
state: Karnataka
city: Bangalore
country: India
facility: M. S. Ramasah Memorial Hospital
state: Karnataka
city: Belgaum
country: India
facility: KLE Hospital, Belgaum
state: Karnataka
city: Mangalore
country: India
facility: Kasturra Medical College, Hospital, Attavar
state: Karnataka
city: Trivandrum
country: India
facility: SCTIMST
state: Kerla
city: Mumbai
country: India
facility: Jaslok Hospital and Research Center
state: Maharastra
city: Chennai
country: India
facility: Apollo Hospitals Educational and Research Foundation
state: Tamilnadu
city: Chieti Scalo
country: Italy
facility: Fondazione Universita di Chieti C.E.S.I. Centro Studi sull'Invecchiamento
state: Ambruzzo
city: Rome
country: Italy
facility: U.O. Neurologia IRCCS San Raffaele Pisana
state: Lazio
city: Messina
country: Italy
facility: IRCCS Centro Neurolesi "Bonino Pulejo"
state: Sicily
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References: