Olanzapine Pamoate Depot Versus Oral Olanzapine on Treatment Outcomes in Outpatients With Schizophrenia - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Schizophrenia
Interventions:	Drug: olanzapine Drug: olanzapine pamoate depot

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Olanzapine Pamoate Depot	405 mg, intramuscular injection, followed 4 weeks later by 150-405 mg flexible dosing, intramuscular injection, every 4 weeks thereafter for 96 weeks, for a total treatment duration of 104 weeks.
Oral Olanzapine	10 mg, oral tablets, once daily for 4 weeks followed by 5-20 mg flexible dosing, oral tablets, once daily, for 100 weeks, for a total treatment duration of 104 weeks.

Participant Flow: Overall Study

	Olanzapine Pamoate Depot	Oral Olanzapine
STARTED	264	260
COMPLETED	119	124
NOT COMPLETED	145	136
Adverse Event	26	25
Clinical Relapse	26	20
Death	0	2
Entry Criteria Exclusion	2	4
Lack of Efficacy	16	7
Lost to Follow-up	21	22
Physician Decision	8	8
Protocol Violation	4	4
Sponsor Decision	3	3
Withdrawal by Subject	39	41

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Olanzapine Pamoate Depot	405 mg, intramuscular injection, followed 4 weeks later by 150-405 mg flexible dosing, intramuscular injection, every 4 weeks thereafter for 96 weeks, for a total treatment duration of 104 weeks.
Oral Olanzapine	10 mg, oral tablets, once daily for 4 weeks followed by 5-20 mg flexible dosing, oral tablets, once daily, for 100 weeks, for a total treatment duration of 104 weeks.

Baseline Measures

	Olanzapine Pamoate Depot	Oral Olanzapine	Total
Number of Participants [units: participants]	264	260	524
Age [units: years] Mean ± Standard Deviation	41.70 ± 10.92	40.12 ± 10.84	40.92 ± 10.90
Gender [units: participants]
Female	89	83	172
Male	175	177	352
Race/Ethnicity, Customized [units: participants]
African	41	47	88
Caucasian	161	164	325
East Asian	23	23	46
Hispanic	26	16	42
Native American	3	1	4
West Asian (Indian sub-continent)	10	9	19
Unspecified	0	0	0
Region of Enrollment [units: participants]
Portugal	9	11	20
France	13	14	27
United States	64	60	124
Taiwan	20	19	39
Slovakia	14	15	29
Greece	20	20	40
Puerto Rico	8	8	16
Canada	20	18	38
Argentina	32	30	62
Brazil	43	44	87
Spain	4	4	8
Romania	17	17	34
Brief Psychiatric Rating Scale (BPRS) Total Score ^[1] [units: Units on a scale] Mean ± Standard Deviation	13.61 ± 5.82	13.11 ± 5.29	13.36 ± 5.56
Length of Current Schizophrenic Episode ^[2] [units: Days] Mean ± Standard Deviation	179.16 ± 152.58	170.73 ± 143.34	174.98 ± 147.98
Age of Onset of Illness [units: Years] Mean ± Standard Deviation	25.95 ± 9.21	26.52 ± 8.65	26.24 ± 8.93
Number of Schizophrenic Episodes or Exacerbations in the Previous 24 Months ^[3] [units: Episodes] Mean ± Standard Deviation	2.78 ± 1.81	2.67 ± 1.43	2.73 ± 1.63
Positivie and Negative Syndrome Scale (PANSS) Scores ^[4] [units: Units on a scale] Mean ± Standard Deviation
PANSS Total	56.78 ± 9.76	56.50 ± 8.70	56.64 ± 9.24
PANSS Positive	12.93 ± 3.62	12.40 ± 3.33	12.67 ± 3.49
PANSS Negative	15.84 ± 4.23	16.28 ± 3.93	16.06 ± 4.08
PANSS General Pathology	28.00 ± 5.45	27.81 ± 4.92	27.91 ± 5.19
Clinical Global Impressions of Severity (CGI-S) ^[5] [units: Units on a scale] Mean ± Standard Deviation	3.24 ± 0.77	3.26 ± 0.66	3.25 ± 0.72

[1]	BPRS is an 18-item clinician-administered scale used to assess the degree of severity of a subject's general psychopathological symptoms. Item scores range from 0 (not assessed) to 7 (extremely severe). Total Scores range from 0 to 126.
[2]	Length of episodes of clinical worsening of schizophrenia symptoms such that hospitalization or an increased level of care surrounding the episode was required. Increased level of care could include the addition of or change to any of the following from a lower level of care: day hospital program; outpatient crisis management; short-term psychiatric treatment in an emergency room; or an addition, increase, or switch of medication.
[3]	Number of episodes of clinical worsening of schizophrenia symptoms such that hospitalization or an increased level of care surrounding the episode was required. Increased level of care could include the addition of or change to any of the following from a lower level of care: day hospital program; outpatient crisis management; short-term psychiatric treatment in an emergency room; or an addition, increase, or switch of medication.
[4]	Assesses the positive symptoms, negative symptoms, and general psychopathology specifically associated with schizophrenia. The scale consists of 30 items. Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Scores for PANSS positive and negative each range from 7 to 49. Scores for General Psychopathology range from 16 to 112. The sum of all 30 items is defined as the PANSS total score and ranges from 30 to 210.
[5]	CGI-S measures severity of illness at baseline. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients).

Outcome Measures

Show All Outcome Measures

1. Primary:

Median Time to Discontinuation for Any Reason (Excluding Sponsor Decision) [ Time Frame: Baseline up to 104 weeks ]

Show Outcome Measure 1

2. Secondary:

Change From Baseline in Heinrich-Carpenter Quality of Life in Schizophrenia Scale (QLS) Total Score at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 2

3. Secondary:

Change From Baseline in 36-Item Short Form Health Survey (SF-36) at 104 Weeks, All Domains and Summary Scores [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 3

4. Secondary:

Change From Baseline in Overall Health Status Assessment Using the EuroQol: 5 Dimensions Questionnaire (EQ-5D) at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 4

5. Secondary:

Change From Baseline in Burden Assessment Scale (BAS) Total Score at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 5

6. Secondary:

Resource Utilization: Number of Outpatient Physician Visits During the Study [ Time Frame: Baseline through 104 weeks ]

Show Outcome Measure 6

7. Secondary:

Resource Utilization: Days of Unpaid Care, Days of Workdays Missed, Days of Paid Care Per Week During the Study [ Time Frame: Baseline through 104 weeks ]

Show Outcome Measure 7

8. Secondary:

Number of Hospitalization Days [ Time Frame: Baseline through 104 weeks ]

Show Outcome Measure 8

9. Secondary:

Change From Baseline in Scale to Assess Unawareness of Mental Disorder (SUMD) Total Score at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 9

10. Secondary:

Change From Baseline in Working Alliance Inventory (WAI) Total Score at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 10

11. Secondary:

Change From Baseline in Schizophrenia Objective Functioning Instrument (SOFI) Global Score at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 11

12. Secondary:

Patient Satisfaction With Medication Questionnaire-Modified (PSMQ) at 104 Weeks (All Items) [ Time Frame: 104 weeks ]

Show Outcome Measure 12

13. Secondary:

Patient Attitude Toward Treatment Using the Drug Attitude Inventory (DAI) Scale Total Score at 104 Weeks [ Time Frame: 104 weeks ]

Show Outcome Measure 13

14. Secondary:

Number of Participants With All-Cause Discontinuations (Excluding Sponsor Decision) [ Time Frame: Baseline through 104 weeks ]

Show Outcome Measure 14

15. Secondary:

Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Scale Scores at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 15

16. Secondary:

Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total and Subscale Scores at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 16

17. Secondary:

Median Time to Relapse [ Time Frame: Baseline to time of relapse (up to 104 weeks) ]

Show Outcome Measure 17

18. Secondary:

Number of Participants Experiencing Relapse [ Time Frame: Baseline through 104 weeks ]

Show Outcome Measure 18

19. Secondary:

Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Score at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 19

20. Secondary:

Resource Utilization: Number of Outpatient Surgeries During the Study, 24 Months After Randomization [ Time Frame: Baseline through 104 Weeks ]

Show Outcome Measure 20

21. Secondary:

Change From Baseline in Weight at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 21

22. Secondary:

Participants With Potentially Clinically Significant (PCS) Weight Gain at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 22

23. Secondary:

Participants With Normal to High Fasting Glucose, Fasting Total Cholesterol, and Fasting Triglycerides [ Time Frame: Baseline through 104 weeks ]

Show Outcome Measure 23

24. Secondary:

Participants With Treatment-Emergent Abnormal High Prolactin at 104 Weeks [ Time Frame: Baseline, 104 weeks ]

Show Outcome Measure 24

25. Secondary:

Participants With Treatment-Emergent High Alanine Transaminase (ALT), Aspartate Transaminase (AST), and Total Bilirubin [ Time Frame: Baseline through 104 Weeks ]

Show Outcome Measure 25

26. Secondary:

Participants Discontinuing Because of an Adverse Event (AE) or Death [ Time Frame: Baseline through 104 weeks ]

Show Outcome Measure 26

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Results for Outcome Measures 17 and 18 were corrected as a result of an identified programming error.

Results Point of Contact:

Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979

No publications provided by Eli Lilly and Company

Publications automatically indexed to this study:

McDonnell DP, Detke HC, Bergstrom RF, Kothare P, Johnson J, Stickelmeyer M, Sanchez-Felix MV, Sorsaburu S, Mitchell MI. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, II: investigations of mechanism. BMC Psychiatry. 2010 Jun 10;10:45.

Detke HC, McDonnell DP, Brunner E, Zhao F, Sorsaburu S, Stefaniak VJ, Corya SA. Post-injection delirium/sedation syndrome in patients with schizophrenia treated with olanzapine long-acting injection, I: analysis of cases. BMC Psychiatry. 2010 Jun 10;10:43.

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00320489 History of Changes
Other Study ID Numbers:	6390, F1D-MC-HGLQ
Study First Received:	April 28, 2006
Results First Received:	September 29, 2010
Last Updated:	January 19, 2012
Health Authority:	United States: Food and Drug Administration