Safety and Efficacy of Olanzapine in the Long-term Treatment for Bipolar I Disorder, Depressed

Safety and Efficacy of Olanzapine (LY170053) in the Long-term Treatment for Patients With Bipolar I Disorder, Depressed

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00618748

Enrollment

101

Registered

2008-02-20

Start date

2008-02-29

Completion date

2010-09-30

Last updated

2011-07-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Bipolar I Disorder

Keywords

Bipolar

Brief summary

To assess the efficacy and safety of olanzapine in the long-term treatment for patients with bipolar I disorder, depressed.

Detailed description

This is an open-label, multi-center, long-term treatment study conducted only in Japanese sites. The subjects are patients who fulfill the diagnostic criteria for bipolar I disorder, most recent episode depressed, as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR) (296.50=unspecified, 296.52=moderate severity, 296.53=severe without psychotic features, 296.54=severe with psychotic features), who have completed Study HGMP (NCT#00510146) and patients who did not participate in Study HGMP who have been recruited to participate in Study HGMS.

Interventions

DRUGOlanzapine

5-20 mg/day, oral, daily

Study design

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

1. Patients must be aged 18 to less than 75 years. 2. 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. 3. All female patients must test negative for pregnancy. 4. 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. 5. Male patients who are not surgically sterilized must agree to use a reliable method of birth control during the study and for 1 month following the last dose of study drug. 6. Patients must fulfill the diagnostic criteria for bipolar I disorder, most recent episode depressed, as defined in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). 7. Patients must have experienced, in the opinion of the investigator, at least one previous manic or mixed episode, as defined in the DSM-IV-TR. 8. Patients must have a current Young Mania Rating Scale (YMRS) Total score =\<8.

Exclusion criteria

1. Is investigator site personnel directly affiliated with this study or their immediate families. 2. Is a Lilly employee. 3. Has previously completed or withdrawn from this study or any other study investigating olanzapine. 4. Is pregnant or nursing. 5. Has a serious, unstable illness such that death is anticipated within 1 year or intensive care unit hospitalization for the disease is anticipated within 6 months.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With Adverse Events Leading to Discontinuation	Baseline through 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	An adverse event (AE) is an untoward medical event associated with the use of the study drug or study procedure, whether or not it is considered related to the study drug or study procedure. Results presented are the percentage of participants who experienced an adverse event that resulted in the discontinuation of the study.

Secondary

Measure	Time frame	Description
Change From Baseline in Weight at Week 24 or Week 48 Endpoint	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	—
Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Week 24 or Week 48 Endpoint	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	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).
Change From Baseline in Young Mania Rating Scale (YMRS) Total Score at Week 24 or Week 48 Endpoint	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	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.
Change From Baseline in Clinical Global Improvement- Bipolar (CGI-BP) at Week 24 or Week 48 Endpoint	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	CGI-BP is a measure of illness severity especially adapted for bipolar illness. It allows rating of mania, depression, and overall illness. The scores for mania, depression, and overall illness each range from 1 (normal, not ill) to 7 (very seriously ill).
Percentage of Participants With Emergence of Mania at Week 24 or Week 48	24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	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.
Change From Baseline in Glucose and Lipid Panel at Week 24 or Week 48 Endpoint	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	—
Percentage of Participants With Extra-Pyramidal Symptoms (EPS) at Week 24 or Week 48	24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	EPS symptoms measured by DIEPSS are grouped into 4 categories: Parkinsonism, akathisia, dystonia, and dyskinesia. Severity ranges from level 0 (none, normal) to 4 (severe). A participant is deemed to have EPS at endpoint if they have an abnormal endpoint. Normal baseline Parkinsonism is defined as a score not ≥3 on 1 item or ≥2 on 2 items; abnormal endpoint is a score ≥3 on 1 item or ≥2 on 2 items, or an increase of 3 on Parkinsonism total. Normal 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.
Change From Baseline in Hemoglobin (HbA1c) at Week 24 or Week 48 Endpoint	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	HbA1c is a test that measures the amount of glycated hemoglobin in the blood over prolonged periods of time.
Change From Baseline in Prolactin at Week 24 or Week 48 Endpoint	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	—
Change From Baseline to in QTcF at Week 24 or Week 48 Endpoint	baseline, 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	Time from electrocardiogram Q wave to the end of the T wave corresponding to electrical systole, fixed correction factor (QTcF interval)
Percentage of Participants With High Suicidality at Week 24 or Week 48	24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)	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. Based upon scores, suicidality is defined as Low (1-8), Medium (9-16), and High (\>=17).

Countries

Japan

Participant flow

Participants by arm

Arm	Count
Pre-Olanzapine Participants who received olanzapine in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	56
Pre-Placebo Participants who received placebo in acute phase of Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 24 weeks.	25
New Olanzapine Participants who did not participate in Study HGMP (NCT#00510146), received olanzapine 5-20 mg/day, orally for 48 weeks.	20
Total	101

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	4	3	8
Overall Study	Physician Decision	3	1	1
Overall Study	Withdrawal by Subject	4	1	5

Baseline characteristics

Characteristic	Pre-Olanzapine	Pre-Placebo	New Olanzapine	Total
Age Continuous	39.31 years STANDARD_DEVIATION 10.48	37.53 years STANDARD_DEVIATION 7.64	39.13 years STANDARD_DEVIATION 9.56	38.84 years STANDARD_DEVIATION 9.61
CGI-BP - Depression	2.23 units on a scale STANDARD_DEVIATION 0.95	2.48 units on a scale STANDARD_DEVIATION 0.82	3.55 units on a scale STANDARD_DEVIATION 1.15	2.55 units on a scale STANDARD_DEVIATION 1.08
CGI-BP - Overall	2.20 units on a scale STANDARD_DEVIATION 0.92	2.40 units on a scale STANDARD_DEVIATION 0.82	3.25 units on a scale STANDARD_DEVIATION 1.02	2.46 units on a scale STANDARD_DEVIATION 1
Clinical Global Improvement- Bipolar (CGI-BP) - Mania	1.09 units on a scale STANDARD_DEVIATION 0.35	1.00 units on a scale STANDARD_DEVIATION 0	1.00 units on a scale STANDARD_DEVIATION 0	1.05 units on a scale STANDARD_DEVIATION 0.26
Montgomery- Asberg Depression Rating Scale (MADRS) Total Score	8.05 units on a scale STANDARD_DEVIATION 7.5	9.72 units on a scale STANDARD_DEVIATION 6.48	16.45 units on a scale STANDARD_DEVIATION 9.03	10.13 units on a scale STANDARD_DEVIATION 8.18
Race/Ethnicity, Customized East Asian	56 participants	25 participants	20 participants	101 participants
Region of Enrollment Japan	56 participants	25 participants	20 participants	101 participants
Sex: Female, Male Female	34 Participants	14 Participants	13 Participants	61 Participants
Sex: Female, Male Male	22 Participants	11 Participants	7 Participants	40 Participants
Young Mania Rating Scale (YMRS) Total Score	0.38 units on a scale STANDARD_DEVIATION 1.1	0.40 units on a scale STANDARD_DEVIATION 0.76	0.45 units on a scale STANDARD_DEVIATION 0.83	0.40 units on a scale STANDARD_DEVIATION 0.97

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	34 / 56	13 / 25	20 / 20
serious Total, serious adverse events	1 / 56	0 / 25	1 / 20

Outcome results

Primary

Percentage of Participants With Adverse Events Leading to Discontinuation

An adverse event (AE) is an untoward medical event associated with the use of the study drug or study procedure, whether or not it is considered related to the study drug or study procedure. Results presented are the percentage of participants who experienced an adverse event that resulted in the discontinuation of the study.

Time frame: Baseline through 24 weeks (pre-olanzapine and pre-placebo) or 48 weeks (new olanzapine)

Population: All randomized Participants.

Arm	Measure	Value (NUMBER)
Pre-Olanzapine	Percentage of Participants With Adverse Events Leading to Discontinuation	7.1 percentage of participants
Pre-Placebo	Percentage of Participants With Adverse Events Leading to Discontinuation	12.0 percentage of participants
New Olanzapine	Percentage of Participants With Adverse Events Leading to Discontinuation	40.0 percentage of participants

Secondary

Change From Baseline in Clinical Global Improvement- Bipolar (CGI-BP) at Week 24 or Week 48 Endpoint

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