Acute Mania, Bipolar Disorder, Manic
Conditions
Brief summary
The purpose of this study is to compare the efficacy and tolerability of ziprasidone versus olanzapine in the treatment of acute mania. An open label extension will further evaluate the efficacy, safety, and tolerability of ziprasidone compared with olanzapine. Study recruitment was stopped due to difficulty in enrolling the targeted number of patients on July 30, 2007. Subjects that were enrolled at the time completed the study as per protocol. There were no safety concerns involved in the decision to stop enrollment. The Last Subject Last Visit was January 10, 2008.
Interventions
Ziprasidone will be initiated at 80 mg/day on Day 1 and titrated to 120 mg/day from Day 3. From Day 7 the dosage may be adjusted on the basis of clinical status between 120 and 160 mg/day.
DRUGolanzapine
Olanzapine will be started at 15 mg/day on Day 1 until Day 7. The dosage will then be adjusted on the basis of clinical status between 15 and 20 mg/day.
Sponsors
Pfizer's Upjohn has merged with Mylan to form Viatris Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a primary diagnosis of Bipolar I Disorder, current episode manic (DSM-IV 296.4x) or mixed (DSM-IV296.6x) as determined by a structured clinical interview (Mini International Neuropsychiatric Interview (MINI)) at screening. * A minimum score of 20 on the YMRS (Youngs Mania Rating Scale).
Exclusion criteria
* Have a diagnosis of learning disability or organic brain syndrome. * Have a substance-induced psychotic disorder or behavioral disturbance thought to be due to substance abuse.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Reduction in Young Mania Rating Scale (YMRS) Score During the Double Blind Phase. | 4 weeks | YMRS is 11-item instrument with scales between 0 to 4 for 7 items and scales between 0 and 8 for 4 items. 0 is normal and either 4 or 8 is the highest level of abnormal, depending on the item. |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Clinical Global Impressions Scale for Use in Bipolar Illness Scores; Montgomery Asberg Depression Scale Scores in the Double Blind Phase. | up to 10 weeks |
| Change From Baseline in Global Assessment of Functioning Scale Scores, Treatment Satisfaction Questionnaire for Medication, Quality of Life Enjoyment and Satisfaction Questionnaire in the Double Blind Phase. | 6 months |
| Percentage of Patients With Symptomatic Remission After 4, 6 and 10 Weeks of Treatment and at the End of the Double-blind Phase. | 4, 6 and 10 weeks |
| Time to Symptomatic Remission in the Double Blind Phase. | up to 10 weeks |
| Percentage of Patients With Clinical Response After 6 Weeks of Double-blind Treatment. | 6 weeks |
| Percentage of Patients With Symptomatic Relapse of Mania and/or Symptomatic Relapse of Depression During the Open Label Phase. | 6 months |
Countries
Germany, Greece, Italy, Spain, Turkey (Türkiye)
Participant flow
Recruitment details
47 centers in Europe.
Pre-assignment details
After a wash out period of at least 24 hours, patients were randomized to ziprasidone or olanzapine.
Participants by arm
| Arm | Count |
|---|---|
| Ziprasidone Ziprasidone was initiated at a dosage of 80 mg/day (40 mg BID) on Day 1 and then was titrated to 120 mg/day (60 mg BID) from Day 3. From Day 7, the dosage was adjusted between 120 to 160 mg/day on the basis of clinical status at the investigator's discretion. | 15 |
| Olanzapine Olanzapine was started at 15 mg/day (15 mg once daily \[QD\]) on Day 1, and remained at this dosage until Day 7. The dosage was adjusted on the basis of clinical status up to 20 mg/day at the investigator's discretion. | 14 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lack of Efficacy | 3 | 3 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | study terminated by sponsor | 1 | 0 |
| Overall Study | Subject no longer willing to participate | 2 | 2 |
| Overall Study | symptomatic deterioration | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
| Overall Study | withdrew patient after SAE resolved | 1 | 0 |
Baseline characteristics
| Characteristic | Ziprasidone | Olanzapine | Total |
|---|---|---|---|
| Age, Customized 18-44 years | 9 participants | 7 participants | 16 participants |
| Age, Customized 45-64 years | 6 participants | 7 participants | 13 participants |
| Sex: Female, Male Female | 10 Participants | 5 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / — | 12 / — |
| serious Total, serious adverse events | 2 / — | 0 / — |
Outcome results
Primary
Mean Reduction in Young Mania Rating Scale (YMRS) Score During the Double Blind Phase.
YMRS is 11-item instrument with scales between 0 to 4 for 7 items and scales between 0 and 8 for 4 items. 0 is normal and either 4 or 8 is the highest level of abnormal, depending on the item.
Time frame: 4 weeks
Population: Study was terminated due to poor recruitment and no efficacy data were summarized due to very low sample size. Only safety data were summarized.
Secondary
Change From Baseline in Clinical Global Impressions Scale for Use in Bipolar Illness Scores; Montgomery Asberg Depression Scale Scores in the Double Blind Phase.
Time frame: up to 10 weeks
Secondary
Change From Baseline in Global Assessment of Functioning Scale Scores, Treatment Satisfaction Questionnaire for Medication, Quality of Life Enjoyment and Satisfaction Questionnaire in the Double Blind Phase.
Time frame: 6 months
Secondary
Percentage of Patients With Clinical Response After 6 Weeks of Double-blind Treatment.
Time frame: 6 weeks
Secondary
Percentage of Patients With Symptomatic Relapse of Mania and/or Symptomatic Relapse of Depression During the Open Label Phase.
Time frame: 6 months
Secondary
Percentage of Patients With Symptomatic Remission After 4, 6 and 10 Weeks of Treatment and at the End of the Double-blind Phase.
Time frame: 4, 6 and 10 weeks
Secondary
Time to Symptomatic Remission in the Double Blind Phase.
Time frame: up to 10 weeks