Bipolar Disorder
Conditions
Brief summary
The primary objective of this trial was to characterize the long-term (up to 40 weeks) safety and tolerability of asenapine in bipolar I disorder subjects who had not completely responded to continuing treatment with lithium or valproic acid (VPA) for the treatment of an acute manic or mixed episodes upon enrollment into the 12-week lead-in trial, A7501008 (NCT00145470). The safety comparison was between the group receiving lithium or VPA and placebo against the group receiving lithium or VPA and asenapine, with the caveat that all subjects may have received benzodiazepine and/or antidepressant rescue medication as needed.
Interventions
DRUGAsenapine
Asenapine 5 or 10 mg twice daily (BID) sublingually for 40 weeks
DRUGPlacebo
Fast-dissolving tablet; twice daily (BID) sublingually for 40 weeks
Sponsors
Organon and Co
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have bipolar I disorder (current episode manic or mixed), be treated with lithium or valproic acid, and have completed the a 12-week lead-in trial
Exclusion criteria
* Have an unstable medical condition or clinically significant laboratory abnormality. * Have a primary diagnosis other than bipolar I disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event | up to 52 weeks | Participants who experienced treatment-emergent adverse events, defined as adverse events reported on or after the first dose of study medication in the 12-week lead-in study through the last dose of study drug + 7 days (or + 30 days for serious adverse events). |
| Number of Participants Who Discontinued Because of an Adverse Event | 40 weeks | Participants who discontinued study medication due to adverse events. |
| Change From Baseline to Week 52 on the Young-Mania Rating Scale (Y-MRS) Score | Baseline and 52 Weeks | The Y-MRS is an 11-item, clinician-rated instrument used for assessing the symptoms of mania. Y-MRS total score range = 0-60; higher scores indicate greater severity of symptoms. |
| Change From Baseline to Week 52 on the Montgomery Asberg Depression Rating Scale (MADRS) Score | Baseline and 52 Weeks | The MADRS is a 10-item clinician-rated scale for assessing the severity of symptoms of depression. MADRS total score range = 0-60; higher scores indicate greater severity of symptoms. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Asenapine Asenapine 5 or 10 mg sublingually twice daily (BID) | 41 |
| Placebo Placebo sublingually BID | 36 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 3 |
| Overall Study | Lack of Efficacy | 3 | 1 |
| Overall Study | Lost to Follow-up | 5 | 9 |
| Overall Study | Reason not provided | 2 | 1 |
| Overall Study | Withdrew Consent | 2 | 7 |
Baseline characteristics
| Characteristic | Asenapine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 39.0 years STANDARD_DEVIATION 11.79 | 38.7 years STANDARD_DEVIATION 13.42 | 38.9 years STANDARD_DEVIATION 12.49 |
| Sex: Female, Male Female | 16 Participants | 18 Participants | 34 Participants |
| Sex: Female, Male Male | 25 Participants | 18 Participants | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 41 | 18 / 36 |
| serious Total, serious adverse events | 9 / 41 | 4 / 36 |
Outcome results
Primary
Change From Baseline to Week 52 on the Montgomery Asberg Depression Rating Scale (MADRS) Score
The MADRS is a 10-item clinician-rated scale for assessing the severity of symptoms of depression. MADRS total score range = 0-60; higher scores indicate greater severity of symptoms.
Time frame: Baseline and 52 Weeks
Population: Intent-to-treat are subjects who took at least one dose of double-blind study medication in the extension study and had at least one Y-MRS and MADRS assessment during the extension study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine | Change From Baseline to Week 52 on the Montgomery Asberg Depression Rating Scale (MADRS) Score | -3.3 Score on a scale | Standard Deviation 9.75 |
| Placebo | Change From Baseline to Week 52 on the Montgomery Asberg Depression Rating Scale (MADRS) Score | -3.9 Score on a scale | Standard Deviation 7.71 |
Primary
Change From Baseline to Week 52 on the Young-Mania Rating Scale (Y-MRS) Score
The Y-MRS is an 11-item, clinician-rated instrument used for assessing the symptoms of mania. Y-MRS total score range = 0-60; higher scores indicate greater severity of symptoms.
Time frame: Baseline and 52 Weeks
Population: Intent-to-treat are subjects who took at least one dose of double-blind study medication in the extension study and had at least one Y-MRS and MADRS assessment during the extension study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Asenapine | Change From Baseline to Week 52 on the Young-Mania Rating Scale (Y-MRS) Score | -17.2 Score on a Scale | Standard Deviation 13.65 |
| Placebo | Change From Baseline to Week 52 on the Young-Mania Rating Scale (Y-MRS) Score | -19.7 Score on a Scale | Standard Deviation 11.81 |
Primary
Number of Participants Who Discontinued Because of an Adverse Event
Participants who discontinued study medication due to adverse events.
Time frame: 40 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asenapine | Number of Participants Who Discontinued Because of an Adverse Event | 10 participants |
| Placebo | Number of Participants Who Discontinued Because of an Adverse Event | 3 participants |
Primary
Number of Participants Who Experienced an Adverse Event
Participants who experienced treatment-emergent adverse events, defined as adverse events reported on or after the first dose of study medication in the 12-week lead-in study through the last dose of study drug + 7 days (or + 30 days for serious adverse events).
Time frame: up to 52 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Asenapine | Number of Participants Who Experienced an Adverse Event | 32 Participants |
| Placebo | Number of Participants Who Experienced an Adverse Event | 25 Participants |