Testing the Ability of JNJ-18038683 to Improve Cognition and Reduce Depressive Symptoms in Stable Bipolar Patients

NCT02466685 | Completed Phase 2 Results

• 1 other identifier: 18038683BCD2001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Bipolar Disorder

Keywords

Bipolar; Depression; Cognition; Cognitive

Outcome Measures

Primary Outcomes (1)

• The 8-week Evaluation of Verbal Fluency Performance After Randomization

  Change in a score of Verbal Fluency from baseline to week 8 A higher amount of change represents a better outcome V.F., as a primary outcome measure, is one of the Cognitive battery tests used to evaluate neurocognitive functions, i.e., speed of processing, attention/vigilance, working memory, verbal learning, and visual learning. The way to calculate the score: the participant is asked to produce as many words as possible from a category in a given time and each correct word gets 1 score Min raw score:0 Max raw score:60

  Baseline and week 8

Secondary Outcomes (2)

• Montgomery-Asberg Depression Rating Scale

  Baseline to week 8

• Clinical Global Impression Severity of the Subject With Bipolar Disorder Scale( CGI-S in BP) Change From Baseline to Week 8

  Baseline to 8 weeks

Study Arms (2)

JNJ-18038683

EXPERIMENTAL

Subjects will be randomized to receive JNJ-18038683 or placebo after the completion of the baseline assessments. Subjects randomized to JNJ-18038683 will receive 10 mg for one week, then titrate to 20 mg for the duration of the trial, with the provision for a single, downward dose adjustment for intolerance, based upon investigator judgment.

Drug: JNJ-18038683

Placebo

PLACEBO COMPARATOR

Placebo treatment for 8 weeks.

Drug: Placebo

Interventions

JNJ-18038683 DRUG

JNJ-18038683 10-20 mg/day tablet for 8 weeks

JNJ-18038683

Placebo DRUG

placebo tablet daily

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Male or female individuals of any race; between 18 to 60 years of age, inclusive.
• Resides in a stable living situation, according to the investigator's judgment.
• 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.
• No more than moderate clinical symptom burden severity, as defined by the following: Montgomery Asberg Depression Rating Scale \< 20 Young Mania Rating Scale \<12
• Individuals medically stable enough to complete an 8 week clinical trial, in the judgment of the investigator
• 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.
• Antidepressant (AD) medications are allowed if the subject has been treated with a stable dose for at least 2 months before screening.
• 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.
• 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.
• Individuals taking ripseridone, lurasidone, or ziprasidone must be currently taking \< doses of 3mg, 40mg, and, 80mg, respectively.
• Patients with a history of compliance with a drug treatment regimen for bipolar disorder, as noted in medical/psychiatric history.
• 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.
• Able to complete cognition assessments in English

You may not qualify if:

• Failure to perform screening or baseline examinations
• Hospitalization within 8 weeks before screening, or change in mood stabilizing or antidepressant medication or dose within 2 months prior to screening.
• Individuals who have participated in another clinical study within the past 2 months.
• Individuals with tardive dyskinesia.
• Individuals with other DSM-V Axis I or Axis II primary diagnoses.
• Diagnosis of alcohol or substance use disorder within the past 3 months.
• Subject assessed to be at significant suicide risk based on responses to the Columbia Suicide Severity Rating Scale (C-SSRS).
• History of myocardial infarction, unstable angina, uncontrolled hypotension or hypertension within 3 months before screening.
• Clinically significant abnormality on screening ECG.
• Alanine transaminase (ALT) or aspartate transaminase (AST) \> 2.5 times the upper limit of normal (ULN).
• History of stroke, brain tumor, head trauma with loss of consciousness, or other clinically significant neurological condition within 12 months before screening.
• Individuals with other uncontrolled medical conditions, in the opinion of the investigator.
• Use of drugs known to be metabolized by CYP2D6.

Sponsors & Collaborators

• Herbert Meltzer: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (1)

Northwestern University Feinberg School of Medicine; Department of Psychiatry and Behavioral Sciences

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• Arshadi M, Elmaadawi AZ, Nasr S, Jayathilake K, Rassnick S, Ford L, Drevets WC, Meltzer HY. Lack of Efficacy of JNJ-18038683 on Cognitive Impairment in Patients With Stable Bipolar Disorder. J Clin Psychopharmacol. 2024 Sep-Oct 01;44(5):481-491. doi: 10.1097/JCP.0000000000001889.

  PMID: 39250138 DERIVED

MeSH Terms

Conditions

Bipolar Disorder; Depression

Interventions

3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydro-1-(phenylmethyl)pyrazolo(3,4-d)azepine 2-hydroxy-1,2,3-propanetricarboxylate

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Results Point of Contact

• Title: Mahdi Arshadi
• Organization: Northwestern University

mahdi.arshadi@northwestern.edu

3123839950

Study Officials

• Herbert Y Meltzer, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychiatry, Physiology and Pharmacology

Study Record Dates

• First Submitted: June 4, 2015
• First Posted: June 9, 2015
• Study Start: September 1, 2015
• Primary Completion: September 1, 2021
• Study Completion: December 1, 2022
• Last Updated: November 14, 2023
• Results First Posted: July 3, 2023

Record last verified: 2023-10

Locations

US (1)