A Clinical Study to Test the Effectiveness of an Investigational Drug to Treat People That Have Major Depressive Episodes When They Have Bipolar 1 Depression

Inclusion Criteria

• Subject is 18 to 65 years of age, inclusive, at the time of informed consent with bipolar I disorder, current episode depressed with or without rapid cycling disease course (≥ 4 episodes of mood disturbance but 450 ms (male subjects) or > 470 ms (female subjects)
• QRS > 110 ms
• PR > 200 ms
• Second- or third-degree atrioventricular block
• Any rhythm other than sinus rhythm, which is interpreted by the Investigator to be clinically significant
• Subject has a history of neuroleptic malignant syndrome (NMS).
• Subject exhibits evidence of severe tardive dyskinesia, severe dystonia, or any other severe movement disorder. Severity is to be determined by the investigator.
• Subject has been diagnosed with type 1 diabetes, or insulin-dependent diabetics.
• Subject who has any abnormal laboratory parameter at screening that indicates a clinically significant medical condition as determined by the investigator. Subjects with fasting blood glucose at screening ≥ 126 mg/dL (7.0 mmol/L) will be excluded from the study. Subjects with fasting blood glucose from 100-125 mg/dL (5.6-6.9 mmol/L) may enter the study based on the approval of the Medical Monitor. Subjects with HbA1c > 7.0% will be excluded. Subjects who are found to have been non-fasting at Screening may be allowed if their blood glucose is 7.0% will be excluded.
• Subject has a prolactin concentration > 100 ng/mL at screening or have a history of pituitary adenoma.
• Subject has a body mass index (BMI) ≥ 40 or < 18 kg/m2.
• Subject has a history of non-response to an adequate (6-week) trial of three or more antidepressants (with or without mood stabilizers) during the current episode.
• Subject is considered by the Investigator to be at imminent risk of suicide or injury to self, others, or answers "yes" to "Suicidal Ideation" item 4 (active suicidal ideation with some intent to act, without specific plan) or item 5 (active suicidal ideation with specific plan and intent) on the C-SSRS assessment at the Screening visit (in the past month [30 days]) or Baseline.
• Subject tests positive for drugs of abuse at screening or baseline. In the event a subject tests positive for cannabinoids (tetrahydrocannabinol), the investigator will evaluate the subject's ability to abstain from cannabis during the study. This information will be discussed with the Medical Monitor for study enrollment consideration.
• Subject has a history of hypersensitivity to more than two distinct chemical classes of drug (e.g., sulfas and penicillins).
• Subjects have received depot neuroleptics unless the last injection was at least one treatment cycle before randomization.
• Subject requires treatment with a drug that consistently prolongs the QTc interval
• Subject has received ECT within 90 days prior to randomization or is expected to require ECT during the study course.
• Subject is currently participating, or has participated in a study with an investigational or marketed compound or device within 6 months prior to signing the informed consent, or has participated in 3 or more studies within 18 months prior to signing the informed consent.