High-Dose Oral Ziprasidone Versus Conventional Dosing in Participants With Residual Schizophrenia Symptoms
Condition: Schizophrenia
MeSH terms: Schizophrenia
Intervention: Ziprasidone 80-160 mg/d; Placebo; Ziprasidone 160 mg/d
Intervention description: Participants will be instructed to take one study capsule of ziprasidone orally twice daily (80 mg/d). After the first week, the study drug will be increased to two capsules twice daily (160 mg/d).; Participants will be instructed to take one study capsule of matching placebo orally twice daily. After the first week, the matching placebo will be increased to two capsules twice daily.; Participants will be taking open-label ziprasidone 80 mg orally twice daily for a total dose of 160 mg/d from at least 3 weeks before randomization to end of study 8 weeks after randomization.
Intervention MeSH terms: Ziprasidone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 131.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Schizophrenia

Summary:

      The primary aims of this study are to assess tolerability of ziprasidone dose escalation to
      320 milligrams per day (mg/d) compared to continued standard treatment (placebo) as measured
      by the Side Effect Checklist, Simpson Angus Scale for Extrapyramidal Symptoms (SAS), Barnes
      Akathisia Scale (BAS), serum prolactin concentrations, vital signs, electrocardiogram (EKG)
      and completion rates and to assess whether ziprasidone dose escalation improves overall
      psychopathology compared to continued standard treatment as measured by the change from
      baseline in the Positive and Negative Syndrome Scale (PANSS) total score and response rates
      as defined by a 20% or greater reduction in PANSS total score.

      The secondary aims of this study are to assess whether ziprasidone dose escalation improves
      psychotic symptoms compared to continued standard treatment as measured by the Positive
      Symptom Subscale of the PANSS, to assess whether ziprasidone dose escalation improves
      negative symptoms compared to standard treatment as measured by the Negative Symptom Subscale
      of the PANSS, to assess whether ziprasidone dose escalation improves depressive symptoms
      compared to continued standard treatment as measured by the Calgary Depression Rating Scale
      (CDRS), and to assess whether ziprasidone dose escalation improves overall functioning with
      the Clinical Global Impression - Severity (CGI-S), Clinical Global Impression - Improvement
      (CGI-I), Global Assessment of Functioning (GAF) and the Schizophrenia Cognition Rating Scale
      (SCoRS).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Schizophrenia or Schizoaffective disorder, any subtype

          -  Age 18-65 years

          -  Treated with ziprasidone at a dose of 160 mg/d for at least 3 weeks with adequate
             compliance

          -  Concomitant standing or other medications as needed (except other antipsychotics and
             those noted as contraindicated in the ziprasidone package insert) are permitted during
             all treatment phases if they were present at a stable dose for at least 6 weeks prior
             to the start of initial ziprasidone treatment

          -  A score of 4 (moderate) or greater on any of the 7 items of the PANSS Positive Symptom
             Subscale

          -  Clinical judgment by the investigator that doses higher than 160 mg/day are warranted
             due to suboptimal clinical outcome despite adequate treatment at that dose

          -  Participant is judged capable of understanding all relevant risks and potential
             benefits of the study and has signed informed consent

          -  Comorbid axis 1 conditions (including anxiety disorders, eating disorders, impulse
             control disorders) are permitted if they have been stable and have not been a primary
             focus of treatment over the previous 6 months

        Exclusion Criteria:

          -  Past or current intolerance of ziprasidone side effects

          -  Presence of significant cardiac disease, including uncompensated congestive heart
             failure, myocardial infarction within the past 6 months or known history of congenital
             long QT interval syndrome

          -  Corrected QT interval (QTc) greater than or equal to 500 milliseconds (msec)

          -  Serum potassium and magnesium concentrations outside of normal limits.

          -  Currently taking any medications which may affect cardiac conduction

          -  Presence of any unstable or untreated medical disorder

          -  Any history of seizures or seizure disorder other than febrile seizures of childhood

          -  History of positive hepatitis B surface antigen

          -  Human immunodeficiency virus (HIV) positive or has diagnosis of acquired immune
             deficiency syndrome (AIDS)

          -  Any abnormal laboratory test that is judged to be clinically significant by the
             investigator

          -  History of neuroleptic malignant syndrome (NMS), hypersensitivity or allergic response
             to antipsychotic therapy, including ziprasidone

          -  History of clozapine treatment for refractory psychotic symptoms

          -  Alcohol or substance dependence within the past 12 months or abuse within the past 3
             months. Any subject with positive urine toxicology or alcohol use that is considered
             abnormal at baseline.

          -  Clinically significant suicidal or homicidal behavior or attempts within past 6 months

          -  Any subject judged by the investigator to present a danger to self or others.

          -  Women of childbearing potential who are not using adequate contraception (oral
             contraceptives, barrier methods or who are clearly abstinent)

          -  Pregnancy or breast-feeding

          -  Any subject who is judged by the investigator to be unable or unlikely to comply with
             all study requirements, including adherence with prescribed medication regimen