Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder; Depression
Intervention: JNJ-18038683; Placebo
Intervention description: JNJ-18038683 10-20 mg/day tablet for 8 weeks; placebo tablet daily
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Bipolar; Depression; Cognition; Cognitive

Summary:

      The goals of this study are to evaluate the efficacy of JNJ-18038683 in an 8 week trial to
      ameliorate the cognitive deficit and reduce residual depressive symptoms in 60 stable bipolar
      outpatients receiving treatment for depression. JNJ-18038683 will be studied and compared
      with placebo as adjunctive treatment to standard pharmacologic treatment for bipolar
      disorder.
    

Eligibility criteria:

        Inclusion Criteria

          1. All participants must have signed an informed consent document indicating they
             understand the purpose of the study and the procedures required for the study and are
             willing to participate by complying with the study procedures and restrictions.

          2. Male or female individuals of any race; between 18 to 60 years of age, inclusive.

          3. Resides in a stable living situation, according to the investigator's judgment.

          4. Diagnosis of bipolar disorder I or II for at least 1 year in duration, as established
             by the SCID-I, and verified with medical records and/or confirmation of diagnosis by
             treating clinician. Patients will be in a nonacute phase at the time of initial
             screening and have been so for at least 1 month.

          5. No more than moderate clinical symptom burden severity, as defined by the following:
             Montgomery Asberg Depression Rating Scale < 20 Young Mania Rating Scale <12

          6. Individuals medically stable enough to complete an 8 week clinical trial, in the
             judgment of the investigator

          7. Women of childbearing potential must have a negative pregnancy serum test at
             screening, negative pregnancy urine test at baseline, and agree to use adequate
             protection (i.e. double barrier method) for birth control.

          8. Antidepressant (AD) medications are allowed if the subject has been treated with a
             stable dose for at least 2 months before screening.

          9. Individuals receiving a single mood stabilizer (e.g., lithium. valproate, or lamictal)
             are allowed if a stable dose has been maintained for at least 2 months prior to
             screening.

         10. Individuals may be receiving one treatment of each the following groups:

             antidepressants, mood stabilizers, and atypical antipsychotics other than clozapine,
             but not more than one from each group.

         11. Individuals taking ripseridone, lurasidone, or ziprasidone must be currently taking <
             doses of 3mg, 40mg, and, 80mg, respectively.

         12. Subjects may be treated with inclusionary antipsychotic drugs as long as they are on a
             stable dose of injectable medication for 2 months or a sable dose of an oral
             medication for 1 month. Exclusionary antipsychotic drugs are listed in Appendix 2 in
             the protocol.

         13. Patients with a history of compliance with a drug treatment regimen for bipolar
             disorder, as noted in medical/psychiatric history.

         14. CNS stimulants (e.g., Adderall, Ritalin) are permitted if the participant is stable on
             their dosage of medication for 1 month before screening and cannot change dosage
             throughout the study.

         15. Able to complete cognition assessments in English

         16. Individuals must demonstrate a substantive cognitive deficit, as measured by the
             Trails A, Hopkins Verbal Learning Test (HVLT), and the Letter Number Span,
             administered at the screening visit. Eligible individuals will have an established
             cognitive deficit as measured by one or more of these tests, scoring below the 75th
             percentile, using comparative norms according to age, gender, and education.

         17. Able to understand and complete cognition assessments

        Exclusion Criteria

          1. Failure to perform screening or baseline examinations

          2. Hospitalization within 8 weeks before screening, or change in mood stabilizing or
             antidepressant medication or dose within 2 months prior to screening.

          3. Individuals who have participated in another clinical study within the past 2 months.

          4. Individuals with tardive dyskinesia.

          5. Individuals with other DSM-V Axis I or Axis II primary diagnoses.

          6. Diagnosis of alcohol or substance use disorder within the past 3 months.

          7. Subject assessed to be at significant suicide risk based on responses to the Columbia
             Suicide Severity Rating Scale (C-SSRS).

          8. History of myocardial infarction, unstable angina, uncontrolled hypotension or
             hypertension within 3 months before screening.

          9. Clinically significant abnormality on screening ECG.

         10. Alanine transaminase (ALT) or aspartate transaminase (AST) > 2.5 times the upper limit
             of normal (ULN).

         11. History of stroke, brain tumor, head trauma with loss of consciousness, or other
             clinically significant neurological condition within 12 months before screening.

         12. Individuals with other uncontrolled medical conditions, in the opinion of the
             investigator.

         13. Use of drugs known to be metabolized by CYP2D6.