Clinical trial NCT00982020: Study in Adolescents With Schizophrenia or Bipolar Disorder
Official title: A Long-Term, Open-Label, Safety Study of Oral Olanzapine in Adolescents With Bipolar I Disorder (Manic or Mixed Episodes) or Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar I Disorder
Schizophrenia
Keywords: safety
schizophrenia
bipolar I (manic or mixed)
adolescents
weight management
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2009-09-22
Enrollment: 203
Sex: ALL
Minimum age (years): 13
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Open-label safety study of oral olanzapine treatment in adolescents, aged 13 to 17 years, with bipolar I disorder (manic or mixed episodes) or schizophrenia.


Eligibility criteria: Inclusion Criteria:

* Participants must have a diagnosis of bipolar I disorder and display an acute manic or mixed episode (with or without psychotic features) or a diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR)and confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime (K-SADS-PL).
* Participants with a diagnosis of schizophrenia must obtain a Brief Psychiatric Rating Scale for Children (BPRS-C) total score \>30, with a minimum score of 3 on at least one of the following items at both screening and randomization - hallucinations, delusions, peculiar fantasies.
* Participants with a diagnosis of bipolar I disorder must have a Young Mania Rating Scale (YMRS) total score greater than or equal to 15 at both screening and randomization.
* Has given assent (when applicable); and has a parent or authorized legal representative who has given informed consent, is reliable, has a level of understanding sufficient to permit participant to perform all tests and examinations required by the protocol, and understands the nature of the study.

Exclusion Criteria:

* History of mental retardation, current comorbid autism, or current comorbid Pervasive Developmental Disorder.
* Have DSM-IV-TR substance (except nicotine and caffeine) dependence within the past 30 days prior to randomization.
* Been judged clinically to be at any suicidal risk.
* History of allergic reaction or hypersensitivity to olanzapine.
* Receiving current pharmaceutical treatment for weight management or are participating in a structured behavioral diet and/or exercise weight loss program.
* Other antipsychotics, mood stabilizers, or anticonvulsants (for mood stabilization) used for the primary study conditions (bipolar I disorder or schizophrenia)
* Have acute, serious, or unstable medical conditions
* Have any illness such that death is anticipated within 1 year or intensive care unit hospitalization for the illness is anticipated within 12 months (365 days).
* Have had one or more seizures without a clear and resolved etiology.
* Baseline alanine aminotransferase (ALT) values greater than or equal to 2 times the upper limit of normal (ULN) of the performing laboratory or aspartate aminotransferase (AST) values greater than or equal to 2 times the ULN or total bilirubin values greater than or equal to 1.5 times the ULN at screening.
* Have leukopenia or history of leukopenia without a clear and resolved etiology or known history of agranulocytosis (absolute neutrophil count \<500 cubic millimeter \[mm\^3\], \<0.5 GI/L, or \<0.5 10E\^3/microliters \[μL\]) during the participant's lifetime.
* Prolactin level of \>200 nanograms per milliliter (ng/mL) \[\>200 micrograms per liter (ug/L), or \>4228 milli-International unit per liter (mIU/L)\] at screening.
* Have QTc (Bazett's) \>450 milliseconds (males) or \>460 milliseconds (females) at screening.
* Previously been randomized in this study and/or participated in a clinical trial of another investigational drug, including olanzapine, within 1 month (30 days) prior to screening.
* Currently prescribed olanzapine for greater than or equal to 5 days within 1 month (30 days) prior to screening.
* Are investigator site personnel directly affiliated with this study and/or their immediate families OR are employed by or representatives of Lilly.
* Pregnant or nursing.
* Have received treatment within the last 30 days with an investigational new drug that has not received regulatory approval for any indication at the time of study entry.
* Treatment with clozapine within 14 days prior to randomization.
* Participants who have used olanzapine (that is, oral olanzapine, intramuscular \[IM\] olanzapine, or olanzapine orally disintegrating tablets) and have had treatment withdrawn due to clinically significant and/or intolerable adverse effects, or who have exhibited a lack of efficacy/response to treatment to olanzapine including treatment resistance.

Primary outcomes:
measure: Mean Change From Baseline to 52 Weeks in Body Mass Index (BMI) for All Participants
timeFrame: Baseline, 52 weeks
Secondary outcomes:
measure: Mean Change From Baseline to Endpoint in Body Mass Index (BMI) for Participants With Duration of Treatment of at Least 6 Months
timeFrame: Baseline, 52 weeks
measure: Time to Event for 7%, 15%, and 25% Weight Gain for All Participants
timeFrame: Baseline up to 52 weeks
measure: Mean Change From Baseline to 52 Weeks in Adolescent Structured Young Mania Rating Scale (YMRS) for Participants With Bipolar I Disorder
timeFrame: Baseline, 52 weeks
measure: Mean Clinical Global Impression of Improvement (CGI-I) at 52 Weeks for All Participants
timeFrame: 52 weeks
measure: Mean Change From Baseline to 52 Weeks in Waist Circumference for All Participants
timeFrame: Baseline, 52 weeks
measure: Mean Change From Baseline to 52 Weeks in Clinical Global Impression - Severity (CGI-S) for All Participants
timeFrame: Baseline, 52 weeks
measure: Mean Change From Baseline to 52 Weeks in Anchored Version of the Brief Psychiatric Rating Scale for Children (BPRS-C) for Participants With Schizophrenia
timeFrame: Baseline, 52 weeks
Other outcomes:
Locations:
city: Lauderhill
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Florida
city: Bloomfield Hills
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Michigan
city: St Louis
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Missouri
city: Bellevue
country: United States
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
state: Washington
city: Poznan
country: Poland
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Torun
country: Poland
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Wroclaw
country: Poland
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Caguas
country: Puerto Rico
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: San Juan
country: Puerto Rico
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Lipetsk
country: Russian Federation
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Moscow
country: Russian Federation
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Petrozavodsk
country: Russian Federation
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Saint Petersburg
country: Russian Federation
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
city: Saratov
country: Russian Federation
facility: For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern Time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References:
citation: Detke HC, DelBello MP, Landry J, Hoffmann VP, Heinloth A, Dittmann RW. A 52-Week Study of Olanzapine with a Randomized Behavioral Weight Counseling Intervention in Adolescents with Schizophrenia or Bipolar I Disorder. J Child Adolesc Psychopharmacol. 2016 Dec;26(10):922-934. doi: 10.1089/cap.2016.0010. Epub 2016 Sep 27.