Melperone (an Anti-Psychotic) in Patients With Psychosis Associated With Parkinson's Disease
Condition: Parkinson's Disease; Psychotic Disorders
MeSH terms: Parkinson Disease; Psychotic Disorders; Mental Disorders
Intervention: Melperone HCl; Melperone HCl; Melperone HCl; Placebo
Intervention description: 20 mg/day. Strength of melperone syrup is 5 mg/mL; 40 mg/day. Strength of melperone syrup is 5 mg/mL; 60 mg/day. Strength of melperone syrup is 5 mg/mL; Syrup formulation
Intervention MeSH terms: Metylperon
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 90.0
Sex: All
Healthy volunteers: No

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.
    

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.