A Study for Assessing Treatment of Patients Ages 10-17 With Bipolar Depression

Bipolar Depression Clinical Trial

Official title:

Study to Assess the Efficacy and Safety of Olanzapine and Fluoxetine Combination Versus Placebo in Patients Ages 10-17 in the Treatment of Major Depressive Episodes Associated With Bipolar I Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00844857
• Other study ID #: 12116
• Secondary ID: H6P-MC-HDAX
• Status: Completed
• Phase: Phase 4
• First received: February 13, 2009
• Last updated: January 16, 2013
• Start date: April 2009
• Est. completion date: February 2012

Study information

• Verified date: January 2013
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationRussia: Ethics CommitteeMexico: Ministry of HealthTurkey: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The main goal of this study is to help answer the following research question(s) and not to treat the child's illness.

• Can this study drug make children with bipolar depression feel better?

• Does this study drug work better than a placebo (sugar pill)?

• Does this study drug cause side effects in children who take it?

• Is this drug safe to use in children? (The study drug is a mixture of olanzapine and fluoxetine)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 291
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 17 Years

Eligibility

Inclusion Criteria:

• Male or female inpatients or outpatients, 10-17 years of age, who have not reached their 18th birthday prior to screening. Patient must weigh at least 20 kilograms (kg) at screening.

• Must meet diagnostic criteria for current major depressive episode of Bipolar I Disorder according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Version (DSM-IV-TR) and confirmed by Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime (K-SADS-PL)

• Patients entering the study will also be scored by the Children's Depression Rating Scale-Revised (CDRS-R) (entry score of greater than or equal to 40) as well as the adolescent-structured Young Mania Rating Scale (YMRS) (entry score of less than or equal to 15 with YMRS Item 1 [elevated mood] score less than equal to 2).

Exclusion Criteria:

• Patients will be excluded if they are, in the opinion of the investigator, actively suicidal

• Have an acute, serious or unstable medical condition

• Have clinically significant laboratory abnormalities

• Have had one or more seizures of unclear etiology

• Have a current or lifetime diagnosis of any of the following according to DSM-IV criteria: Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, Delusional Disorder, Psychotic Disorder Not Otherwise Specified, Delirium of any type, Amnestic Disorder, any Substance-Induced Disorder, or any Psychotic Disorder due to a General Medical Condition, unless there is substantive reason to believe patient was misdiagnosed

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Depression
• Bipolar Disorder
• Depression
• Depressive Disorder

Intervention

Drug:
• Olanzapine Fluoxetine Combination (OFC)
OFC doses are capsules of 3 milligrams (mg) olanzapine and 25 mg fluoxetine (3/25), 6/25, 12/25, 6/50, or 12/50 mg to be taken orally once daily in the evening for 8 weeks.
• Placebo
Orally, once daily in the evening for 8 weeks.

Locations

Country	Name	City	State
Russian Federation	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.	Lipetsk
Russian Federation	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.	Moscow
Russian Federation	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.	Saratov
Russian Federation	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.	Stavropol
Russian Federation	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.	Tver
Russian Federation	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.	Yaroslavl
United States	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.	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With at Least One Treatment-Emergent Incident of Parkinsonism Up to Week 8	Parkinsonism was measured using the Simpson-Angus Scale with a total scores range from 0 to 40. A score > 3 was considered abnormal. Simpson-Angus Scale consists of 10 items, each rated on a 5-point scale, 0 (complete absence of the condition) to 4 (presence of the condition in extreme form).	Baseline, Week 8	Yes
Other	Percentage of Participants With at Least One Treatment-Emergent Incident of Dyskinesia Up to Week 8	Dyskinesia was measured using the Abnormal Involuntary Movement Scale (AIMS) a 12-item scale designed to record the occurrence of dyskinetic movements. Items 1 through 10 are rated on a 5-point scale: 0 (no dyskinetic movements) to 4 (severe dyskinetic movements). Items 11 and 12 are yes/no questions regarding the dental condition of a patient. Total score (0-40) is obtained by adding the scores of the first 10 items. An abnormal result is defined as having a score =3 for at least 1 of the first 7 items or a score =2 for at least two of the first 7 items.	Baseline, Week 8	Yes
Other	Change From Baseline in the Quality of Life Questionnaire for Children and Adolescents (KINDL) Kid and Kiddo Combined Scale Up to Week 8	The KINDL consists of 24 Likert-scale items. Kid-KINDL was administered to ages 8-11 and Kiddo-KINDL to ages 12-16. Total scores were standardized to a 0 (lowest quality of life) to 100 (highest quality of life). LS mean was adjusted for baseline, country, and treatment.	Baseline, Week 8	Yes
Other	Change From Baseline in Weight Up to Week 8	Weight LS mean was adjusted for baseline and treatment.	Baseline, Week 8	Yes
Other	Change From Baseline in Fasting Metabolic Parameters Up to Week 8	Fasting glucose, fasting cholesterol and fasting triglycerides. LS means were adjusted for baseline and treatment.	Baseline, Week 8	Yes
Other	Change From Baseline in Alanine Aminotransferase/Serum Glutamic-Pyruvic Transaminase (ALT/SGPT) Up to Week 8	ALT/SGPT LS mean was adjusted for baseline and treatment.	Baseline, Week 8	Yes
Other	Change From Baseline in Prolactin Up to Week 8	Prolactin LS mean was adjusted for baseline and treatment.	Baseline, Week 8	Yes
Other	Change From Baseline in Electrocardiogram (ECG) QTcF Interval Up to Week 8	QTcF is defined as ECG QT interval corrected for heart rate using the Fridericia correction factor.	Baseline, Week 8	Yes
Primary	Change From Baseline in the Children's Depression Rating Scale Revised (CDRS-R) Total Score at Week 8	CDRS-R Total score measures the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. A rating of 1 indicates normal functioning. Total scores range from 17 to 113. In general, scores below 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. Least Square (LS) mean was adjusted for baseline, country, treatment, visit, and treatment times (*) visit interaction.	Baseline, Week 8	No
Secondary	Percentage of Participants With Remission Up to Week 8	Remission is defined as a CDRS-R total score less than or equal to (=)28, and Young Mania Rating Scale (YMRS) total score = 8 and Clinical Global Impressions-Bipolar Version (CGI-BP) total score =3. CDRS-R is a 17-item scale measuring presence/severity of depression in children and is scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. Scores range: 17 to 113. Scores <20 indicate an absence of depression, scores 20 to 30 indicate borderline depression, scores 40 to 60 indicate moderate depression. The YMRS is an 11-item scale measuring severity of manic episodes; 4 items are rated on a scale from 0 (symptoms not present) to 8 (symptom extremely severe) with remaining items rated on a scale from 0 (symptoms not present) to 4 (symptom extremely severe). YMRS score ranges from 0 to 60. CGI-BP measures participant's overall severity of bipolar symptoms. Scores range: 1 (normal, not at all ill ) to 7 (among the most extremely ill participants).	Baseline up to Week 8	No
Secondary	Percentage of Participants With Response Up to Week 8	Response is defined as a CDRS-R total score greater than or equal to (=)50% reduction from baseline and YMRS elevated mood score =2. CDRS-R Total score measure the presence and severity of depression in children. The scale consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. Scores range: 17 to 113. In general, <20 indicate an absence of depression, scores 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptoms not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptoms not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60.	Baseline up to Week 8	No
Secondary	Percentage of Participants in Each Improvement Category Up to Week 8	CDRS-R scores: No/low improvement is < 25 percent (%) of maximum reduction from baseline. Mild improvement: maximum reduction from baseline on CDRS-R score = 25% up to <50% and YMRS elevated mood score = 2. Moderate improvement: maximum reduction from baseline on CDRS-R score =50% and <75% and YMRS elevated mood score = 2. Major improvement: maximum reduction from baseline on CDRS-R score =75% and YMRS elevated mood score = 2. CDRS-R measures presence/severity of depression in children. Scale is 17 items scored 1-to-5- or 1-to-7. Rating of 1 indicates normal function. Scores range: 17 to 113. Scores < 20 absence of depression, scores 20 to 30 borderline depression, scores 40 to 60 indicate moderate depression. YMRS is an 11-item scale that measures severity of manic episodes. Four items rated 0 (symptoms not present) to 8 (symptom extremely severe). Remaining items rated 0 (symptoms not present) to 4 (symptom extremely severe). Score range: 0 to 60.	Baseline up to Week 8	No
Secondary	Change From Baseline in the YMRS Total Score at Week 8	The YMRS is an 11-item scale measuring the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total scores ranges: 0 to 60. LS mean was adjusted for baseline, country, treatment, visit, and treatment * visit interaction.	Baseline, Week 8	No
Secondary	Change From Baseline in the Clinical Global Impression Scale - Bipolar Version (CGI-BP) Score at Week 8	CGI-BP measures severity of illness for bipolar illness. Scores range: 1 (normal, not ill at all) to 7 (among the most extremely ill patients). LS mean was adjusted for baseline, country, treatment, visit, and treatment * visit interaction.	Baseline, Week 8	No
Secondary	Change From Baseline in the CDRS-R Total Score Up to Week 8	CDRS-R Total score measure the presence and severity of depression in children and consists of 17 items scored on a 1-to-5- or 1-to-7-point scale. Rating of 1 indicates normal function. Total scores range from 17 to 113. In general, scores < 20 indicate an absence of depression, scores of 20 to 30 indicate borderline depression, and scores of 40 to 60 indicate moderate depression. LS mean was adjusted for baseline, country, and treatment.	Baseline, Week 8	No
Secondary	Percentage of Participants With at Least One Treatment-Emergent Incident of Akathisia Up to Week 8	Akathisia was measured using the Barnes Akathisia Rating Scale where the global scores range from 0 (absent) to 5 (severe) and a score = 2 is considered abnormal.	Baseline up to Week 8	Yes
Secondary	Percentage of Participants With Treatment Emergent Suicidal Ideation or Behavior Up to Week 8	Columbia-Suicide Severity Rating Scale (C-SSRS) captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Percentage of participants with suicidal ideation, behavior, and acts are provided. Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions, which includes wish to be dead, and 4 different categories of active suicidal ideation. Suicidal behavior: a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal act: a "yes" answer to actual attempt or completed suicide.	Baseline up to Week 8	Yes
Secondary	Percentage of Participants With at Least One Incident of Worsening of Mania Up to Week 8	Worsening of mania was defined as YMRS score of =20 and a CGI severity of mania score of = 5 at the same visit. The YMRS is an 11-item scale measuring severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe) with remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. CGI measures severity of the participant's overall severity of bipolar symptoms and scores range from 1 (normal) to 7 (among the most extremely ill participants).	Baseline up to Week 8	Yes
Secondary	Change From Baseline in Symptoms of Attention-Deficit/Hyperactivity Disorder Up to Week 8	Attention Deficit/Hyperactivity Disorder Rating Scale-IV-Parent Version (ADHDRS-IV-PI): Investigator Administered and Scored measures the 18 symptoms contained in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of Attention-Deficit/Hyperactivity Disorder. Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often). Scores range: 0 to 54. The LS mean was adjusted for baseline and treatment.	Baseline up to Week 8	No
Secondary	Change From Baseline in the Quality of Life Questionnaire for Children and Adolescents (KINDL) Parent Scale Up to Week 8	The KINDL consists of 24 Likert-scale items. Total scores were standardized to a 0 (lowest quality of life) to 100 (highest quality of life). LS mean was adjusted for baseline, country, and treatment.	Baseline, Week 8	No