Olanzapine Treatment of Patients With Bipolar I Disorder

Lilly

Status and phase: Completed; Phase 3

Conditions: Depression, Bipolar

Treatments: Drug: Placebo; Drug: Olanzapine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00510146

F1D-MC-HGMP (Other Identifier)

11218 (Registry Identifier)

Details and patient eligibility

About

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

Full description

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

Enrollment: 514 patients

Sex: All

Ages: 18 to 64 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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514 participants in 3 patient groups, including a placebo group

Olanzapine

Experimental group

Description:

During double-blind treatment, participants receive olanzapine at a dose of 5 milligram (mg) which is increased to 10 mg per day no later than 3-7 days after randomization (Baseline). Subsequent dose increases above 10 mg (up to a maximum of 20 mg per day) are permitted in 5 mg per day increments, based upon tolerability and symptoms. Dosing may be decreased by any number of decrements, however dosing below 5 mg requires study discontinuation.

Treatment:

Drug: Olanzapine

Placebo

Placebo Comparator group

Description:

Matching placebo administered once daily, by mouth during double-blind treatment.

Treatment:

Drug: Placebo

Olanzapine (open-label treatment period)

Experimental group

Description:

During open-label treatment, participants randomized to placebo in double-blind period will receive olanzapine 5 mg starting at Week 6. Participants randomized to olanzapine must be at a 5 mg olanzapine dose at Week 7. Those on higher doses will be reduced between Week 6 and Week 7 (10 mg reduced to 5 mg; 15 mg reduced to 10 mg and then to 5 mg at Week 7; 20 mg reduced to 15 mg and then 10 mg to dosing at 5 mg at Week 7). Dose increases beyond Week 7 are permitted and at the investigator's discretion.

Treatment:

Drug: Olanzapine