Olanzapine Treatment of Patients With Bipolar I Disorder

Eli Lilly and Company514 enrolled

Overview

The purpose of this study is to assess whether olanzapine is superior to placebo in patients with bipolar depression.

1. Dose range and administration mode: Oral Olanzapine 5mg - 20mg/day 2. Duration: 1. Screening phase is 2-28 days. 2. Double-blind treatment phase is 6 weeks 3. Open-label extension phase is 18 weeks

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

514

Conditions

Depression, Bipolar

Interventions

OlanzapineDRUG

5-20 mg, oral, once daily, for 24 weeks (participants randomized to olanzapine in double-blind treatment period) or 18 weeks (participants randomized to placebo in double-blind treatment period).

PlaceboDRUG

placebo tablets, oral, once daily at bedtime, 6 weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Each patient must be reliable, have a level of understanding sufficient to perform all tests and examinations required by the protocol, and must understand the nature of the study and have provided informed consent * All female patients must test negative for pregnancy and females of breast-feeding potential must agree not to breastfeed an infant during the study and for 1 month following the last dose of study drug * Patients must fulfill the criteria for a major depressive episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) as well as criteria for bipolar I disorder, depressed, as defined in the DSM-IV-TR, based on clinical assessment and confirmed by the structured diagnostic interview, the Mini International Neuropsychiatric Interview (MINI), at study entry * Patients must have a current 17-item Hamilton Depression Rating Scale (HAMD-17) score greater than or equal to 18 at Visit 1 and Visit 2 * Patients must have a current Young Mania Rating Scale (YMRS) total score less than or equal to 8 at Visit 2. Exclusion Criteria: * Has received treatment within the past 30 days with a drug (not including study drug) that has not received regulatory approval for any indication at the time of study entry * Has participated in a clinical trial of another investigational drug, including olanzapine, within 1 month (30 days) before study entry * Was previously treated with olanzapine and had bipolar depression considered to be treatment-resistant to olanzapine or to olanzapine in combination with an available selective serotonin reuptake inhibitor (SSRI) * Is experiencing (at the time of study entry) a current episode of bipolar depression that is greater than 90 days in duration * Has been treatment-resistant to any therapy prescribed for bipolar depression when olanzapine alone or with an SSRI prescribed at an appropriate dose and duration

Locations (16)

Outcomes

Primary Outcomes

Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score (Acute Phase)

The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

Time frame: Baseline, Endpoint (Week 6)

Secondary Outcomes

Percentage of Participants With Symptomatic Response at Endpoint (Acute Phase)

Response is defined as a reduction (from baseline to endpoint) of 50% or more in the MADRS total score. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

Time frame: Endpoint (Week 6)

Percentage of Participants With Symptomatic Remission At Any Time (Acute Phase)

Percentage of participants with symptomatic remission at any time as defined as a score of less than or equal to 12 in the MADRS total score. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

Time frame: Baseline through Endpoint (Week 6)

Change From Baseline to Endpoint in Clinical Global Improvement- Bipolar (CGI-BP) Severity of Illness Scores-Mania, Depression, Overall Bipolar Illness Scores (Acute Phase)

CGI-BP is a measure of illness severity especially adapted for bipolar illness. It allows rating of mania, depression, and overall illness. The score ranges from 1 (normal, not ill) to 7 (very seriously ill).

Time frame: Baseline, Endpoint (Week 6)

Percentage of Participants With Recovery (Acute Phase)

Data from ClinicalTrials.gov

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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.

Beijing, China

Changsha, China

Chengdu, China

Guangzhou, China

Hangzhou, China

Harbin, China

Kunming, China

Nanjing, China

Shanghai, China

Wuhan, China

...and 6 more locations

Percentage of participants with recovery defined as a value of less than or equal to 12 in the MADRS total score for at least 4 weeks of post-baseline treatment. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

Time frame: Baseline through Endpoint (Week 6 )

Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Acute Phase)

The YMRS is an 11-item scale that measures 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 score ranges from 0 to 60.

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Hamilton Depression Rating Scale-17 (HAMD-17) Total Score (Acute Phase)

The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).

Time frame: Baseline, Endpoint (Week 6)

Percentage of Participants With Major Depressive Episode at Endpoint on Mini International Neuropsychiatric Interview (MINI), Depressive Episode Module (Acute Phase)

In the MINI Major Depressive Episode module, participants are asked a series of Yes/No questions to determine whether or not they are experiencing a major depressive episode or a major depressive episode with melancholic features.

Time frame: Endpoint (Week 6)

Percentage of Participants With Current Hypomanic Episode at Endpoint on MINI Manic Episode Module (Acute Phase)

In the MINI Manic Episode module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing hypomanic or manic episodes.

Time frame: Endpoint (Week 6)

Percentage of Participants With Psychotic Disorders and Mood Disorders With Psychotic Features at Endpoint on MINI Psychotic Disorders Module (Acute Phase)

In the MINI Psychotic Features Episode module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing mood disorder with psychotic features or current psychotic disorders.

Time frame: Endpoint (Week 6)

Percentage of Participants With Alcohol Dependence and Abuse at Endpoint on MINI Alcohol Dependence/Abuse Module (Acute Phase)

In the MINI Alcohol Abuse and Dependence Module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing symptoms indicating current alcohol dependence or abuse.

Time frame: Endpoint (Week 6)

Percentage of Participants With Non-Alcohol Psychoactive Substance Use Disorder at Endpoint on MINI Substance Dependence/Abuse Module (Acute Phase)

In the MINI Substance Dependence and Abuse Module, participants are asked a series of Yes/No questions to determine whether or not they are currently experiencing symptoms indicating current non-alcohol substance use dependence or abuse.

Time frame: Endpoint (Week 6)

Percentage of Participants With Emergence of Mania During the Study (Acute Phase)

Emergence of mania is defined as first occurrence of score of \>=15 in the YMRS total score in the post-baseline period of Acute Phase. The YMRS is an 11-item scale that measures 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 score ranges from 0 to 60.

Time frame: Baseline through Endpoint (Week 6)

Percentage of Participants With Extra-Pyramidal Symptoms (EPS) At Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Acute Phase)

EPS symptoms measured by DIEPSS are grouped into 4 categories: parkinsonism, akathisia, dystonia, and dyskinesia. Severity is assessed at 5 levels, from level 0 (none, normal) to level 4 (severe). For Parkinsonism, normal baseline is defined as a score not \>=3 on 1 item nor \>=2 on 2 items; abnormal endpoint is defined as a score \>=3 on 1 item or \>=2 on 2 items, or an increase of 3 on Parkinsonism total. Baseline akathisia, dystonia and dyskinesia is defined as a score \<2; abnormal endpoint is a score \>=2 or an increase \>= 2 from that baseline score.

Time frame: Endpoint (Week 6)

Change From Baseline to Endpoint in Blood Pressure (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Weight (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Albumin (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Alanine Amino Transferase/Serum Glutamate Pyruvate Transaminase (ALT/SGPT), Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT), Gamma Glutamyl Transferase (GGT)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Direct Bilirubin, Total Bilirubin, Uric Acid (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Erythrocyte Count (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Hematocrit (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Hemoglobin A1c (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Hemoglobin (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Prolactin (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Urinalysis (UA)- Specific Gravity (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change in Electrocardiogram (ECG) From Baseline to Endpoint (Acute Phase)

Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval); Bazett-Corrected QT Interval (QTcB interval).

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in Heart Rate (Acute Phase)

Time frame: Baseline, Endpoint (Week 6)

Change From Baseline to Endpoint in MINI Suicidality Total Scores (Acute Phase)

The MINI module C (MINI-C) is a rating scale for severity of suicidal thoughts and behaviors. The MINI-C is composed of 12 Yes/No questions with variable scores assigned to each question. The scale ranges from 0 to 52 with higher scores indicating a greater presence of suicidal thoughts and/or behaviors.

Time frame: Baseline, Endpoint (Week 6)

Number of Participants With Adverse Events (Acute Phase)

Please refer to the Adverse Event overview for details regarding adverse events and serious adverse events.

Time frame: Baseline through Week 6 (Acute Phase)

Percentage of Participants With Symptomatic Response in Montgomery-Asberg Depression Rating (MADRS) Depression Rating (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)

Percentage of Participants With Symptomatic Remission in the MADRS Total Score (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)

Percentage of Participants With Recovery (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)

Change From Baseline to Endpoint in Young Mania Rating Scale (YMRS) Total Score (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Percentage of Participants With Emergence of Mania During the Study (Open-Label Phase)

Emergence of mania is defined as first occurrence of score of \>=15 in the YMRS total score in the Open-Label Extension. The YMRS is an 11-item scale that measures 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 score ranges from 0 to 60.

Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)

Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Endpoint As Measured by Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS) (Open-Label Phase)

Time frame: Endpoint (Week 24)

Change From Baseline to Endpoint in Blood Pressure (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Weight (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/ Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Albumin and Total Protein (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Alkaline Phosphatase, Creatinine Phosphokinase (CPK), GGT (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Chloride (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Creatinine (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Erythrocyte Count (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Hemoglobin (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Platelet Count (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Prolactin (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Uric Acid (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Glucose and Lipids (Cholesterol, Triglycerides, HDL Cholesterol, LDL Cholesterol) (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in ECG (Open-Label Phase)

Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval); Bazett-Corrected QT Interval (QTcB interval).

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Change From Baseline to Endpoint in Heart Rate (Open-Label Phase)

Time frame: Baseline (End of Acute Phase/Week 6), Endpoint (Week 24)

Percentage of Participants With High Suicidality at Endpoint (Open-Label Phase)

Time frame: Endpoint (Week 24)

Number of Participants With Adverse Events (Open-Label Phase)

Please refer to the Adverse Event overview for details regarding adverse events and serious adverse events.

Time frame: Baseline (End of Acute Phase/Week 6) through Endpoint (Week 24)