Study of Preladenant for the Treatment of Antipsychotic Induced Movement Disorders in Participants With Schizophrenia (Study P04628)
Condition: Akathisia, Drug-Induced; Dyskinesia, Drug-Induced; Parkinsonian Disorders
MeSH terms: Dyskinesias; Parkinsonian Disorders; Psychomotor Agitation; Dyskinesia, Drug-Induced; Akathisia, Drug-Induced; Schizophrenia
Intervention: Preladenant; Placebo
Intervention description: capsules; capsules
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Anti-Dyskinesia Agents; Antipsychotic Agents

Summary:

      This study was designed to determine if preladenant (SCH 420814, MK-3814) can reduce
      drug-induced involuntary movements in participants with schizophrenia or schizoaffective
      disorder. Participants were to be evaluated for two 14-day treatment periods with a 3-week
      washout period between treatment periods. The primary outcome measure, Extrapyramidal Symptom
      Rating Score (ESRS), was to be evaluated frequently during the treatment periods.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males or females >=18 and <=65 years old with a body mass index of 17-31 kg/m^2.

          -  Diagnosed with Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV)
             criteria for schizophrenia/schizoaffective (depressive type) disorder with
             antipsychotic-induced extrapyramidal symptoms (parkinsonism, akathisia, dystonia, or
             tardive dyskinesia [TD]) based on the following ESRS criteria:

               -  parkinsonism, dystonia, or TD - ESRS score >=2 on 2 items or >=3 on one item,

               -  akathisia - ESRS score >=3 on two items,

          -  Has total ESRS score >8.

          -  Must be receiving neuroleptics at a stable dosage for at least 7 days prior to
             enrollment.

          -  Clinical laboratory tests, physical exam, and electrocardiogram must be within normal
             limits or clinically acceptable to the investigator/sponsor (except signs and symptoms
             of Schizophrenia/Schizoaffective disorder).

          -  Liver function tests must be within normal limits at screening.

          -  Participant screening for drugs with a high potential for abuse must be negative.

          -  Must be free of any clinically significant disease other than
             schizophrenia/schizoaffective disorder that would interfere with the study evaluations
             or procedures.

          -  Must have a level of understanding sufficient to communicate with research staff,
             cooperate with all protocol required tests and examinations, and be able to adhere to
             protocol restrictions and schedules.

          -  Must be able to understand the nature of the study and must be willing to sign an
             informed consent (required for each patient or the patient's authorized legal
             representative) prior to study enrollment.

          -  Females must have a follicle stimulating hormone (FSH) >=40 lU/L and be greater than
             12 months since last menses or surgically sterilized.

        Exclusion Criteria:

          -  Has a history of clinically significant local or systemic infectious disease within 4
             weeks prior to initial treatment administration, clinically significant food or drug
             allergy, seizures, alcohol/drug dependence, previous neurosurgery, or coronary artery
             disease (including myocardial infarction [MI], cerebrovascular disease [stroke,
             transient ischemic attack (TIA)], or peripheral arterial disease).

          -  Has participated in a clinical trial of an investigational drug within 60 days or
             donated blood within the preceding 90 days prior to the start of the study.

          -  Has circulating human immunodeficiency virus (HIV), hepatitis C antibodies, or
             hepatitis B surface antigen.

          -  Is allergic to preladenant (SCH 420814, MK-3814) or any excipients in preladenant
             capsules (citric acid, lactose monohydrate, croscarmellose sodium, magnesium stearate
             [nonbovine, vegetable grade], Food, Drug, and Cosmetic [FD&C] blue, titanium dioxide,
             gelatin-national formulary [NF]).

          -  Females who are not surgically sterilized or postmenopausal.

          -  Males who are sexually active and who do not agree to use a barrier method of birth
             control during the study.

          -  Has severe/uncontrolled hypertension. (Participants with hypertension well controlled
             on a stable dose of standard anti-hypertensive medication for at least 4 weeks before
             randomization are eligible.)

          -  Has atrioventricular (AV) block, sick sinus syndrome, congestive heart failure, or
             participants with electrocardiograms (ECGs) consistent with ischemic heart disease, or
             significant Q waves.

          -  Has DSM-IV criteria of dementia (except due to schizophrenia/and schizoaffective
             disorder), or individuals who in the opinion of the investigator are not able to
             understand or comply with the study procedures or the instructions of the staff or are
             socially incapable to participate in the study.

          -  Does not comply with the requirement that participants should not use any drugs
             (except acetaminophen and other allowed medications) within 2 weeks prior to the
             study, nor alcohol (wine, beer) within 72 hours prior to drug administration.

          -  Judged clinically to be at suicidal risk too serious to be included in this study.

          -  Has received electroconvulsive therapy within 30 days before randomization.

          -  Is currently taking clozapine.