Comparison of Two Forms of Oxcarbazepine for the Treatment of Bipolar Depression

This study will use the CCI Engaged Practice platform (EngagedPractice.Com) and will be
conducted by a central "meta-site" reviewing eligibility, obtaining consent, randomizing
subjects to treatment groups, training local care providers (LCP) to function as sub-
investigators and monitoring outcomes.

Subjects will be randomized to six weeks of treatment with extended release oxcarbazepine or
immediate release oxcarbazepine,while remaining under the care of their existing LCP.

LCP's will receive sub-investigator training for Good Clinical Practice, Human subjects
protection, and all protocol specified assessments and procedures.

A computer simulated rater will collect outcomes (including MADRS, YMRS, PHQ-9, and adverse
effects) ahead of each routine clinical visit and provide Measure-based Guidance o the LCP in
the form of pre-assessment reports. The primary outcome variable is "treatment effectiveness"
operationally defined as the response rate X the completion rate.

Inclusion Criteria: The protocol is designed to collect evidence from subjects during the
course of routine clinical care. Enrollment is limited to consenting subjects with a
current local care provider who agrees that oxcarbazepine is a reasonable next step in
managing their bipolar depression

1. Adults male or female, 18-65 years of age, inclusive, at the time of informed consent.

2. Able to access the internet for computer administered ratings.

3. Lifetime mood disorder Diagnosis of Bipolar disorder I or II and a current episode
meeting criteria for MDE with or without mixed features according to the Diagnostic
and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) at screen and baseline
and confirmed by the Collaborative Care Initiative (CCI) review of pre-assessment
including bipolarity index score ≥ 50,

4. Severity of current MDE at least moderate depression as defined by Montgomery Asberg
Depression Rating Scale (MADRS) ≥20 and least three symptoms of DSM 5 MDE criteria
meet threshold for counting toward a current MDE diagnosis (item scores ≥4) at screen
and baseline.

5. Duration of current MDE at baseline is at least 4 weeks in and no longer than 2 years

6. Cycle frequency does not exceed 8 mood episodes in the past 365 days.

7. Current treatment regimen stable for at least 4 weeks and must include at least one of
three acceptable medication types, but no more than 1 from each class: lithium, one
dopamine-blocking agent, one standard antidepressant medication.

8. The LCP agrees that treatment with oxcarbazepine is appropriate, completes study
training, and agrees to complete all protocol management and record keeping
requirements.

9. Any urine toxicology screens for drugs of abuse (cocaine, amphetamines, barbiturates,
opiates, benzodiazepines, and cannabinoids) and alcohol in the 6 months prior to the
baseline visit have been negative. Note any positive test result(s) for
benzodiazepines accompanied by confirmation of a prescription for a valid medical
reason will be allowed.

10. Negative urine pregnancy test at screen or baseline visit.

11. Sexually active women, unless surgically sterile (at least six months prior to study
drug administration) or at least one year post-menopausal, must have used an effective
method of avoiding pregnancy (including oral, transdermal, or implanted contraceptives
intrauterine device, female condom with spermicide, diaphragm with spermicide,
cervical cap, abstinence, use of condom with spermicide by sexual partner or sterile
[at least six months prior to study drug administration] sexual partner) for at least
four weeks prior to study drug administration, and must have agreed to continue using
such precautions through the End of Study visit. Cessation of birth control after this
point was to be discussed with a responsible physician.

12. At least one set of clinical labs including serum sodium, creatinine and TSH have been
obtained and within normal limits within the 3 months prior to the baseline visit.

Exclusion Criteria:

1. Inability to provide informed consent in English

2. Current or lifetime diagnosis of epilepsy

3. Pregnancy, breastfeeding or refusal to use birth control

4. Another current Axis I diagnosis that is the primary focus of current treatment

5. Substance or alcohol abuse/dependence at least 6 months prior enrollment

6. Clinically significant abnormal results on clinical laboratories (including serum
Creatinine, Sodium, and TSH) at baseline visit or within the prior 3 months.

7. Has started treatment with an FDA approved agent for Bipolar depression within the
past 4 weeks

8. Has received treatment with a long-acting injectable antipsychotic or
electroconvulsive therapy during the 2 months prior screening

9. If psychotropic medication outside of study limits is required (Note: Subjects may
receive any concomitant medications prescribed by their local care providers with the
following specific exceptions: Anti-anxiety medications (anxiolytics) exceeding
equivalent of lorazepam 2 mg/d.

10. Any long-acting injectable antipsychotic, More than one dopamine blocking agent, More
than one standard antidepressant agent, FDA approved treatments for Bipolar depression
(quetiapine, lurasidone, the combination of olanzapine and fluoxetine), or
Electroconvulsive therapy.)

11. Last dose of another anticonvulsant agent taken in the current week or within 5
half-lives of discontinuation (whichever is longer) prior to enrollment in the study

12. Current treatment requires ongoing anti-anxiety medications (Anxiolytics) exceeding
equivalent of lorazepam 2 mg/d.

13. Use of oxcarbazepine (OXC) for treatment of current episode

14. Previous known hypersensitivity to OXC or other related drugs, such as carbamazepine.

15. History or presence of clinically significant, chronic medical condition, (e.g.,
hyponatremia, any neurological, gastrointestinal, endocrine, cardiovascular,
pulmonary, hematological, immunologic, renal, hepatic or metabolic disease) that in
the opinion of the clinician or investigator may affect the safety of the subject and
the participation to the trial.

16. Active Suicidality (MADRS item 10 >4) Active suicidal plan/intent or active suicidal
thoughts in the past 6 months. Any suicide attempt within two years of the screening
assessment.