E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10004939 |
E.1.2 | Term | Bipolar I disorder |
E.1.2 | System Organ Class | 10037175 - Psychiatric disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the efficacy of ELND005 compared to placebo as adjunctive maintenance therapy in patients with BPD I.
To assess the safety and tolerability of ELND005 in BPD I patients. |
|
E.2.2 | Secondary objectives of the trial |
To assess additional efficacy, pharmacokinetic (PK), and pharmacodynamic (PD) endpoints. |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
P-MRS study to assess the effects of ELND005 on brain levels of myo-inositol and additional metabolites.
24-hour urine collection study to determine ELND005 and uric acid levels. |
|
E.3 | Principal 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.
|
|
E.4 | Principal 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.
- Has a history of rapid cycling BPD I with ≥ 8 cycles within the last year.
- 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
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Time to recurrence of any mood episode (depressive, manic/hypomanic, or mixed episode), whichever occurs first, during the randomized phase of the study. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
-Proportion of study patients with recurrence of any mood episode
-Time to recurrence of a depressive episode
-Time to recurrence of a manic/hypomanic or a mixed episode
-Proportion of study patients with recurrence of a depressive episode
-Proportion of study patients with recurrence of a manic/hypomanic or a mixed episode
-Mean change from baseline to endpoint in HAM-A
-Mean change from baseline to endpoint in CGI-BP-S for mania, depression, and overall bipolar illness |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 70 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Canada |
Czech Republic |
France |
Lithuania |
Poland |
Romania |
Spain |
Turkey |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
A study patient will be considered to have completed Study BPD201 at the end of the 48-week Double-blind randomisation Phase (i.e. Week 48 or End of Study [EOS]).
This definition is based on the timepoint for primary endpoint assessment. A safety follow-up phase of 6 weeks will occur following the Week 48 or End of Study [EOS] visit. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |