Bipolar 1 Disorder
Conditions
Brief summary
The primary purpose of this study is to determine whether ELND005 is effective in the maintenance treatment of bipolar 1 disorder when added to other therapies.
Interventions
Sponsors
Elan Pharmaceuticals
OPKO Health, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Meets the DSM-IV-TR criteria for BPD I by the SCID, prior to the Screening Visit. * Has a history in the last 3 years of ≥ 1 manic or mixed episodes of sufficient severity that required hospitalization and/or treatment with a mood stabilizer or antipsychotic, or confirmed by a family member or medical records to ensure the episode fulfills the DSM-IV-TR criteria. * Has experienced a mood episode of any polarity within 4 months prior to the Screening Visit and responded to StOC therapy. * Is euthymic at the Screening Visit (ie, score of ≤ 12 on the MADRS and a score of ≤ 12 on the Y-MRS). * Is receiving maintenance treatment for his or her BPD I with either LTG or VPA; on stable doses for past 4 weeks and therapeutic drug levels (total VPA 50--125 µg/mL and LTG 10-50 µmol/L or as deemed appropriate by the investigator). Dose adjustments made for tolerability reasons will be acceptable. A study patient must meet the following additional criteria to be eligible for randomization in the Double-blind Randomization Phase of this study: \- Maintained in a stable euthymic state during Phase 1, defined as Y-MRS and MADRS scores of ≤ 12, with the following exceptions: a maximum of 2 nonconsecutive excursions will be allowed throughout Phase 1. Excursions are defined as Y-MRS or MADRS scores \>12 but ≤ 16.
Exclusion criteria
* Woman of childbearing potential who is unwilling or unable to use an acceptable method of birth control or is using a prohibited contraceptive method. * Is found to be actively suicidal on the C-SSRS (answer of yes to question 4 or 5 \[current or over the last 30 days\]) or a score of ≥4 on the MADRS item 10 at the Screening Visit. * Has suboptimally treated thyroid disease as evidenced by thyroid-stimulating hormone (TSH) \>3 mIU/L at the Screening Visit. * Has received electroconvulsive therapy (ECT) during the current episode or within 6 months prior to the Screening Visit. * Has an estimated glomerular filtration rate \<40 mL/min/1.73 m2 according to the Modification of Diet in Renal Disease formula. A study patient who meets ANY of the above and ANY of the criteria below will not be eligible for enrollment in the Double-blind Randomization Phase of this study: * Has current signs or symptoms of psychosis. * Has become actively suicidal as defined by C-SSRS answer of yes to question 4 or 5 (current or over the last 30 days) and/or has a score of ≥4 on MADRS item 10.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Emergent Adverse Events | up to 48 weeks | The study was terminated early so no efficacy analysis was done, safety data are reported. |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of Study Participants With Recurrence of Any Mood Episode | up to 48 weeks |
| Time to Recurrence of a Depressive Episode | up to 48 weeks |
| Time to Recurrence of a Manic/Hypomanic or a Mixed Episode | up to 48 weeks |
Countries
Bulgaria, Canada, Czechia, France, Poland, Romania, Spain, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants | 309 |
| Total | 309 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open Treatment Phase 1 | Adverse Event | 10 | 0 | 0 |
| Open Treatment Phase 1 | Death | 1 | 0 | 0 |
| Open Treatment Phase 1 | Did not remain in a stable remission | 30 | 0 | 0 |
| Open Treatment Phase 1 | Lost to Follow-up | 19 | 0 | 0 |
| Open Treatment Phase 1 | Physician Decision | 9 | 0 | 0 |
| Open Treatment Phase 1 | Protocol Violation | 7 | 0 | 0 |
| Open Treatment Phase 1 | Sponsor Decision | 79 | 0 | 0 |
| Open Treatment Phase 1 | Withdrawal by Subject | 25 | 0 | 0 |
| Randomization Phase 2 | Adverse Event | 0 | 1 | 1 |
| Randomization Phase 2 | Lost to Follow-up | 0 | 1 | 2 |
| Randomization Phase 2 | Mood episode recurrence | 0 | 8 | 2 |
| Randomization Phase 2 | Physician Decision | 0 | 0 | 2 |
| Randomization Phase 2 | Pregnancy | 0 | 1 | 1 |
| Randomization Phase 2 | Protocol Violation | 0 | 1 | 1 |
| Randomization Phase 2 | Sponsor Decision | 0 | 42 | 45 |
| Randomization Phase 2 | Withdrawal by Subject | 0 | 8 | 7 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous Phase 1(n=309) | 44.3 years STANDARD_DEVIATION 11.09 |
| Age, Continuous Phase 2 ELND005 500mg BID(n=64) | 44.6 years STANDARD_DEVIATION 10.61 |
| Age, Continuous Phase 2 Placebo (n=65) | 44.5 years STANDARD_DEVIATION 10.65 |
| Race/Ethnicity, Customized Hispanic or Latino Phase 1 | 23 participants |
| Race/Ethnicity, Customized Hispanic or Latino Phase 2 ELND005 500 BID | 6 participants |
| Race/Ethnicity, Customized Hispanic or Latino Phase 2 Placebo | 4 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino Phase 1 | 284 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino Phase 2 ELND005 500 BID | 58 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino Phase 2 Placebo | 60 participants |
| Race/Ethnicity, Customized Unknown Phase 1 | 2 participants |
| Race/Ethnicity, Customized Unknown Phase 2 ELND005 500 BID | 0 participants |
| Race/Ethnicity, Customized Unknown Phase 2 Placebo | 1 participants |
| Region of Enrollment Europe | 99 participants |
| Region of Enrollment North America | 210 participants |
| Sex/Gender, Customized Phase 1 Female | 163 participants |
| Sex/Gender, Customized Phase 1 Male | 146 participants |
| Sex/Gender, Customized Phase 2 ELND005 500 BID Female | 32 participants |
| Sex/Gender, Customized Phase 2 ELND005 500 BID Male | 32 participants |
| Sex/Gender, Customized Phase 2 Placebo Female | 31 participants |
| Sex/Gender, Customized Phase 2 Placebo Male | 34 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 153 / 309 | 45 / 65 | 45 / 64 |
| serious Total, serious adverse events | 12 / 309 | 3 / 65 | 3 / 64 |
Outcome results
Primary
Treatment Emergent Adverse Events
The study was terminated early so no efficacy analysis was done, safety data are reported.
Time frame: up to 48 weeks
Population: TEAEs reported for Phase 2 were from the entire study period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open Treatment Phase 1 ELND005 500 mg BID | Treatment Emergent Adverse Events | 153 participants |
| Phase 2 Placebo | Treatment Emergent Adverse Events | 45 participants |
| Phase 2 ELND005 500 mg BID | Treatment Emergent Adverse Events | 45 participants |
Secondary
Proportion of Study Participants With Recurrence of Any Mood Episode
Time frame: up to 48 weeks
Population: Study was prematurely terminated, no data were collected for this Outcome Measure
Secondary
Time to Recurrence of a Depressive Episode
Time frame: up to 48 weeks
Population: Study was prematurely terminated, no data were collected for this Outcome Measure
Secondary
Time to Recurrence of a Manic/Hypomanic or a Mixed Episode
Time frame: up to 48 weeks
Population: Study was prematurely terminated, no data were collected for this Outcome Measure