Clinical trial NCT00403546: High-Dose Oral Ziprasidone Versus Conventional Dosing in Participants With Residual Schizophrenia Symptoms
Official title: High-Dose Oral Ziprasidone Versus Conventional Dosing in Schizophrenia Patients With Residual Symptoms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Schizophrenia
Keywords: Schizophrenia
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2006-11-23
Enrollment: 131
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Number of Events Recorded Based on Ziprasidone Side Effects Checklist During Randomized Trial
timeFrame: From Baseline up to Week 8
measure: Change From Baseline in Simpson Angus Scale for Extrapyramidal Symptoms (SAS)
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8
measure: Change From Baseline in the Barnes Akathisia Scale (BAS)
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8
measure: Number of Participants With High and Low Levels in Serum Prolactin Concentration
timeFrame: Baseline, Week 8
measure: Vital Signs: Systolic and Diastolic Blood Pressure Levels
timeFrame: Baseline, Week 1, Week 2, Week 4, Week 6, Week 8
measure: Electrocardiogram (EKG): Number of Participants With an Increase From Baseline to Corrected QT (QTc) Interval >/= 500 Milliseconds (Msec)
timeFrame: 6 hours after dosing of Weeks 1, 2 and 8
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8
measure: Percentage of Participants With Response
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8
measure: Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Score
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8
measure: Number of Treatment-emergent Adverse Events During Randomized Trial
timeFrame: From Baseline up to Week 8
Secondary outcomes:
measure: Change From Baseline in Positive Subscale Score of PANSS
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8
measure: Change From Baseline in PANSS Negative Subscale Score
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8
measure: Change From Baseline in the Calgary Depression Rating Scale (CDRS) Total Score
timeFrame: Baseline, Week 2, Week 4, Week 6, Week 8
measure: Change From Baseline in Clinical Global Impression- Severity (CGI-S) Score
timeFrame: Baseline, Week 8
measure: Change From Baseline in Clinical Global Impression - Improvement (CGI-I) Score
timeFrame: Baseline, Week 8
measure: Change From Baseline in Global Assessment of Functioning (GAF) Score
timeFrame: Baseline, Week 8
measure: Change in Schizophrenia Cognition Rating Scale (SCoRS) Score
timeFrame: Baseline, Week 8
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Fall River
country: United States
facility: Corrigan Mental Health Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Touchstone innovare
state: Michigan
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Brooklyn
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: New York
country: United States
facility: The Lieber Center for Schizophrenia Research - Columbia University
state: New York
city: Orangeburg
country: United States
facility: Nathan Kline Institute
state: New York
city: Butner
country: United States
facility: Duke University - John Umstead Hospital
state: North Carolina
city: Plano
country: United States
facility: The Mech Center
state: Texas
Study officials:
affiliation: Massachusetts General Hospital
name: Donald Goff, M.D.
role: PRINCIPAL_INVESTIGATOR
References: