Bipolar Disorder
Conditions
Keywords
mixed episode
Brief summary
1. To assess the acute and long-term bimodal efficacy of iloperidone (IL), as an adjunct to ongoing treatment with lithium (Li) or divalproex (DIV) or lamotrigine (LAM) or any combination of the three thereof, in a group of patients with an index episode of a mixed state in BD. 2. To assess background, baseline features, and behavioral components which characterize treatment response/non-response in the acute and long term management of MS
Detailed description
This is a prospective 20-week, open-label study of iloperidone added to ongoing treatment regimen with mood stabilizers (Li or DIV or LAM or any combination of these) in the acute and maintenance treatment of MS- Total number of subjects: 40. Severity of the illness and psychopathological features will be measured by the following rating scales: YMRS, MADRS, CGI-S and GAS, and the BISS . The study will monitor the safety and tolerability of the combination iloperidone plus mood stabilizers. Efficacy Measures: Primary efficacy measures include 1) Mixed effects repeat measure of change from baseline in BISS total score and, secondarily, manic and depression subscale scores. Secondary Efficacy Measures: 1) response defined as 50% reduction in YMRS and MADRS and 2) Time to intervention or discontinuation for any mood episode. Iloperidone will be initiated at 2 mg at hs on day 1 with increase to 4mg at hs on day 2, 8 mg at hs on day 3. All patients will have iloperidone titrated to receive a dosage of at least 12 mg a day. Dosages can be titrated up to 24 mg a day based on tolerability and clinical indication. Dosage of iloperidone can be reduced to 6 mg a day if patients develop side effects necessitating a reduction in the dosage
Interventions
DRUGiloperidone
Qualifying subjects will take iloperidone starting at 2mg and up to a minimum of 12mg, maximum of 24mg, for 20 weeks in conjunction to the subjects current lithium, and or divalproex, and or lamotrigine.
Sponsors
Novartis Pharmaceuticals
Vanda Pharmaceuticals
The University of Texas Health Science Center at San Antonio
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female; 2. Age 18 years and older 3. Patients on: * Li at a stable dose for 2 weeks or longer, and a serum level at screening of greater than or equal to 0.5 mEq/l OR * DIV dose for 2 weeks or longer, and a serum level at screening of greater than or equal to 45 ug/ml OR * LAM (dosage/day ≥100mg) at a stable dose for 2 weeks or longer OR * Any combination 3a, 3b, or 3c 4. Patients meeting DSM-IV TR diagnosis of bipolar disorder, I or II, as assessed using the MINI, (Sheehan et al., 1998) PLUS any ONE of criteria 5 or 6 or 7 5. Patients meeting DSM-IV TR diagnostic criteria for a mixed manic episode with Young Mania Rating Scale (YMRS) score\>/=14 and Montgomery Asberg Depression Rating Scale (MADRS) score\>/=14 6. Patients meeting the criteria for a manic/hypomanic episode for at least 2 days with the simultaneous presence of Young Mania Rating Scale (YMRS) score\>/=14 PLUS Montgomery Asberg Depression Rating Scale (MADRS) score\>/=14 ; 7. Patients meeting DSM-IV TR diagnostic criteria for a major depressive episode with the simultaneous presence of MADRS score\>/=14 PLUS meeting the criteria for a manic/hypomanic episode for at least 2 days with the simultaneous presence of Young Mania Rating Scale (YMRS) score\>/=14
Exclusion criteria
1. Patients with a current Axis I diagnosis of schizophrenia, schizophreniform disorder, schizotypal disorder, bipolar disorder with psychotic sub-type that requires hospitalization, drug induced mania or AIDS induced mania 2. Women with a positive pregnancy test or who are lactating 3. Women of child-bearing potential who are not practicing a clinically accepted method of contraception 4. Patients with general medical conditions that contraindicate psychoactive medications or uncontrolled medical disorder or central nervous system diseases. 5. Patients whose clinical status requires inpatient or day hospital treatment 6. History of severe side effects associated with therapeutic doses of Li, DIV, LAM 7. Alcohol or drug dependent at time of enrollment 8. Suicidal at time of enrollment. 9. Current or previous exposure to iloperidone 10. Patients taking medication that cause QTC prolongation 11. Patients with serious cardiac disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measure of Response by Change From Baseline to End of Study in BISS Depression and Mania Scale Scores | Baseline and 20 weeks | The Bipolar Inventory of Symptoms Scale is a reliable and valid measure which assesses Depression and Mania symptoms of bipolar disorder. There are 42 items; each item is rated on a 0-4 scale. The BISS is a clinician-rated instrument. The Scale is rated as follows: 0 Not at all 1. Slight 2. Mild 3. Moderate 4. Severe Each of the 42 items is rated separately, with a score, based on the most recent 7 day period. For Depression: Items 1-21 items of the assessment are summed up and multiplied by 4 to give a cumulative score out of 84. The higher the score, the more severe the depression. For Mania: Items 22-42 are summed up and multiplied by 4 to give a cumulative score out of 84. The higher the score, the more severe the mania. The mean is calculated from the change in score between baseline and week 20. |
Countries
United States
Participant flow
Recruitment details
Recruitment occurred April 2013 to April 2015 from patients in the clinic or from responders to t.v. advertisements.
Pre-assignment details
Subjects who met inclusion criteria at screening visit were started on study medication at visit 2.
Participants by arm
| Arm | Count |
|---|---|
| Open Label Iloperidone open label iloperidone (oral tablet, 6mg-24mg, QD, 20 weeks) as adjunct to current lithium, divalproex, or lamotrigine.
iloperidone: Qualifying subjects will take iloperidone starting at 2mg and up to a minimum of 12mg, maximum of 24mg, for 20 weeks in conjunction to the subjects current lithium, and or divalproex, and or lamotrigine. | 31 |
| Total | 31 |
Baseline characteristics
| Characteristic | Open Label Iloperidone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 31 / 31 |
| serious Total, serious adverse events | 0 / 31 |
Outcome results
Primary
Measure of Response by Change From Baseline to End of Study in BISS Depression and Mania Scale Scores
The Bipolar Inventory of Symptoms Scale is a reliable and valid measure which assesses Depression and Mania symptoms of bipolar disorder. There are 42 items; each item is rated on a 0-4 scale. The BISS is a clinician-rated instrument. The Scale is rated as follows: 0 Not at all 1. Slight 2. Mild 3. Moderate 4. Severe Each of the 42 items is rated separately, with a score, based on the most recent 7 day period. For Depression: Items 1-21 items of the assessment are summed up and multiplied by 4 to give a cumulative score out of 84. The higher the score, the more severe the depression. For Mania: Items 22-42 are summed up and multiplied by 4 to give a cumulative score out of 84. The higher the score, the more severe the mania. The mean is calculated from the change in score between baseline and week 20.
Time frame: Baseline and 20 weeks
Population: Subjects who are currently treated with mood stabilizers (Lithium, Divalproex or Lamotrigine), with a diagnosis of Bipolar Disorder I or II.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Mean Change in Depression for Study Completers | Measure of Response by Change From Baseline to End of Study in BISS Depression and Mania Scale Scores | 35.7 percentage change in score on BISS scale |
| Mean Change in Mania for Study Completers | Measure of Response by Change From Baseline to End of Study in BISS Depression and Mania Scale Scores | 61.8 percentage change in score on BISS scale |
| Mean Change in Depression for All Study Participants | Measure of Response by Change From Baseline to End of Study in BISS Depression and Mania Scale Scores | 25 percentage change in score on BISS scale |
| Mean Change in Mania for All Study Participants | Measure of Response by Change From Baseline to End of Study in BISS Depression and Mania Scale Scores | 48 percentage change in score on BISS scale |
Comparison: BISS Outcomes: Mean changes in depression and mania for study completers were measured. The a priori hypothesis was a mean change of 50%.p-value: <0.0094t-test, 2 sided
Comparison: BISS Outcomes: Mean changes in mania for study completers were measured. The a priori hypothesis was a mean change of 50%.p-value: <0.0001t-test, 2 sided